B Cell Lymphoma

Adding ibrutinib to chemotherapy did not improve outcomes for children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL), an interim analysis of the SPARKLE trial showed.

Among 51 patients aged 1-30 years with mature B-NHL that had been diagnosed before age 18, there was no significant difference in the primary endpoint of event-free survival (EFS) between patients assigned on a 2:1 basis to receive either ibrutinib (Imbruvica) plus one of two chemotherapy regimens or to chemotherapy alone. In fact, EFS was shorter among patients assigned to ibrutinib, although a larger proportion of these patients had previously received rituximab, a known factor for poor prognosis, reported Amos Burke, MD, from Cambridge (England) University.

The trial was stopped for futility in May 2020, after a median follow-up of 17.97 months.

“Further studies are required to determine the optimal therapy for patients with relapsed, mature B-NHL, especially those who have received prior rituximab,” he said in an audio walk-through of a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a very challenging patient population because they historically have had a very poor survival rate,” commented Paul J. Galardy, MD, a pediatric hematologist/oncologist at the Mayo Clinic in Rochester, Minn., who was not involved in the study.

“The field has struggled to improve outcomes for these patients in part because there are relatively few patients per year with relapsed refractory mature B-cell lymphoma due to the very effective nature of the up-front therapy. This makes new clinical trials difficult to perform,” he said.
 

Poor prognosis

Ibrutinib, an inhibitor of Bruton tyrosine kinase, is approved in the United States for treatment of marginal zone lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as other indications, all in adults only. It has also been shown to have activity against B-NHL in preclinical and early human trials, Dr. Burke said.

Given the poor prognosis of children and young adults with relapsed/refractory mature B-NHL – a 2-year overall survival (OS) of 30% or less with chemoimmunotherapy – the investigators tested whether adding ibrutinib to the standard of care could improve outcomes.

They enrolled patients with relapsed/refractory B-NHL in first relapse or primarily refractory to conventional therapy, with measurable disease (greater than 1 cm) by CT, bone marrow involvement, or cerebrospinal fluid with blasts. The patients were required to have Karnofsky-Lansky performance scores of 50 or greater.

The histologies included Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt-like lymphoma, Burkitt leukemia, primary mediastinal B-cell lymphoma, and other unspecified types.

Dr. Burke reported results on 48 patients included in the May 2020 analysis, plus 3 additional patients who were enrolled between the data cutoff for the first analysis and the meeting of the independent data monitoring committee where the decision was made to stop the trial.

A total of 35 patients were randomized to receive ibrutinib with either the RICE (rituximab plus ifosfamide, carboplatin, and etoposide) or RVICI (rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone) regimen. All of these patients received treatment on study.

Of the 18 patients randomized to receive either RICE or RVICI alone, 1 did not receive any cycles of chemoimmunotherapy.

At the data cutoff for the updated analysis in November 2020, 14 patients assigned to ibrutinib and 4 assigned to chemoimmunotherapy alone remained on study; no patients in either arm were still receiving therapy.

A total of 17 patients assigned to the combination arm died and 4 withdrew consent. In the chemoimmunotherapy-alone arm, 10 died and 2 withdrew consent.

In both arms, patients were treated until either completing three cycles of therapy, start of conditioning treatment prior to stem cell transplantation, disease progression, or unacceptable toxicity.

In the ibrutinib arm, the median EFS was 5.36 months, compared with 6.97 months with chemoimmunotherapy alone, translating into a hazard ratio for EFS with ibrutinib of 1.078 (nonsignificant).

The respective median overall survival was 13.44 versus 11.07 months,

Subgroup analysis showed that EFS and OS did not differ significantly by age, histology, background regimen, or central nervous system or bone marrow involvement. ­

Overall response rates were 68.6% in the ibrutinib arm, and 81.3% in the chemoimmunotherapy arm. The respective complete response rates were 8.6% and 18.8%, and partial response rates were 60% and 62.5%.

The overall treatment-emergent adverse event (TEAE) profile was similar between the treatment arms, although six patients in the ibrutinib arm versus one in the chemoimmunotherapy arm experienced a major hemorrhage. One patients in the ibrutinib arm died from pulmonary hemorrhage.

Dr. Burke noted that, although the numbers were small, the failure to see a difference in efficacy between study arms may have been caused in part by a greater number of patients assigned to ibrutinib who had received prior treatment with rituximab (85.7% vs. 56.3%).
 

Not the right partner?

“The results of this study would suggest that ibrutinib is not the right agent. This is not altogether unexpected,” Dr. Galardy said. “The benefit of ibrutinib in adults with mature B-cell lymphoma is primarily based on biological characteristics of lymphomas that develop in older individuals.”

He noted that mature B-cell lymphoma in older adults is often of the activated B-cell subtype, which frequently has mutations that make it sensitive to ibrutinib. In contrast, children, adolescents, and young adults more commonly have the germinal center B-cell subtype that doesn’t have similarly targetable mutations.

He added that, although the reasons for poor prognosis in patients with prior rituximab exposure are unclear, “it is likely that patients who have recurrent or refractory disease after therapy that included rituximab may have developed resistance to this drug. Since both arms of this study included rituximab as a component of the therapy, the patients with prior exposure to this drug may have had reduced benefit of the additional rituximab, compared with those who had not received the drug before.”

The SPARKLE trial was funded by Janssen Research & Development. Dr. Burke disclosed consultancy fees from Janssen and others. Dr. Galardy is an equity holder in Abbott and AbbVie.

Adding ibrutinib to chemotherapy did not improve outcomes for children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL), an interim analysis of the SPARKLE trial showed.

Among 51 patients aged 1-30 years with mature B-NHL that had been diagnosed before age 18, there was no significant difference in the primary endpoint of event-free survival (EFS) between patients assigned on a 2:1 basis to receive either ibrutinib (Imbruvica) plus one of two chemotherapy regimens or to chemotherapy alone. In fact, EFS was shorter among patients assigned to ibrutinib, although a larger proportion of these patients had previously received rituximab, a known factor for poor prognosis, reported Amos Burke, MD, from Cambridge (England) University.

The trial was stopped for futility in May 2020, after a median follow-up of 17.97 months.

“Further studies are required to determine the optimal therapy for patients with relapsed, mature B-NHL, especially those who have received prior rituximab,” he said in an audio walk-through of a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a very challenging patient population because they historically have had a very poor survival rate,” commented Paul J. Galardy, MD, a pediatric hematologist/oncologist at the Mayo Clinic in Rochester, Minn., who was not involved in the study.

“The field has struggled to improve outcomes for these patients in part because there are relatively few patients per year with relapsed refractory mature B-cell lymphoma due to the very effective nature of the up-front therapy. This makes new clinical trials difficult to perform,” he said.
 

Poor prognosis

Ibrutinib, an inhibitor of Bruton tyrosine kinase, is approved in the United States for treatment of marginal zone lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as other indications, all in adults only. It has also been shown to have activity against B-NHL in preclinical and early human trials, Dr. Burke said.

Given the poor prognosis of children and young adults with relapsed/refractory mature B-NHL – a 2-year overall survival (OS) of 30% or less with chemoimmunotherapy – the investigators tested whether adding ibrutinib to the standard of care could improve outcomes.

They enrolled patients with relapsed/refractory B-NHL in first relapse or primarily refractory to conventional therapy, with measurable disease (greater than 1 cm) by CT, bone marrow involvement, or cerebrospinal fluid with blasts. The patients were required to have Karnofsky-Lansky performance scores of 50 or greater.

The histologies included Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt-like lymphoma, Burkitt leukemia, primary mediastinal B-cell lymphoma, and other unspecified types.

Dr. Burke reported results on 48 patients included in the May 2020 analysis, plus 3 additional patients who were enrolled between the data cutoff for the first analysis and the meeting of the independent data monitoring committee where the decision was made to stop the trial.

A total of 35 patients were randomized to receive ibrutinib with either the RICE (rituximab plus ifosfamide, carboplatin, and etoposide) or RVICI (rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone) regimen. All of these patients received treatment on study.

Of the 18 patients randomized to receive either RICE or RVICI alone, 1 did not receive any cycles of chemoimmunotherapy.

At the data cutoff for the updated analysis in November 2020, 14 patients assigned to ibrutinib and 4 assigned to chemoimmunotherapy alone remained on study; no patients in either arm were still receiving therapy.

A total of 17 patients assigned to the combination arm died and 4 withdrew consent. In the chemoimmunotherapy-alone arm, 10 died and 2 withdrew consent.

In both arms, patients were treated until either completing three cycles of therapy, start of conditioning treatment prior to stem cell transplantation, disease progression, or unacceptable toxicity.

In the ibrutinib arm, the median EFS was 5.36 months, compared with 6.97 months with chemoimmunotherapy alone, translating into a hazard ratio for EFS with ibrutinib of 1.078 (nonsignificant).

The respective median overall survival was 13.44 versus 11.07 months,

Subgroup analysis showed that EFS and OS did not differ significantly by age, histology, background regimen, or central nervous system or bone marrow involvement. ­

Overall response rates were 68.6% in the ibrutinib arm, and 81.3% in the chemoimmunotherapy arm. The respective complete response rates were 8.6% and 18.8%, and partial response rates were 60% and 62.5%.

The overall treatment-emergent adverse event (TEAE) profile was similar between the treatment arms, although six patients in the ibrutinib arm versus one in the chemoimmunotherapy arm experienced a major hemorrhage. One patients in the ibrutinib arm died from pulmonary hemorrhage.

Dr. Burke noted that, although the numbers were small, the failure to see a difference in efficacy between study arms may have been caused in part by a greater number of patients assigned to ibrutinib who had received prior treatment with rituximab (85.7% vs. 56.3%).
 

Not the right partner?

“The results of this study would suggest that ibrutinib is not the right agent. This is not altogether unexpected,” Dr. Galardy said. “The benefit of ibrutinib in adults with mature B-cell lymphoma is primarily based on biological characteristics of lymphomas that develop in older individuals.”

He noted that mature B-cell lymphoma in older adults is often of the activated B-cell subtype, which frequently has mutations that make it sensitive to ibrutinib. In contrast, children, adolescents, and young adults more commonly have the germinal center B-cell subtype that doesn’t have similarly targetable mutations.

He added that, although the reasons for poor prognosis in patients with prior rituximab exposure are unclear, “it is likely that patients who have recurrent or refractory disease after therapy that included rituximab may have developed resistance to this drug. Since both arms of this study included rituximab as a component of the therapy, the patients with prior exposure to this drug may have had reduced benefit of the additional rituximab, compared with those who had not received the drug before.”

The SPARKLE trial was funded by Janssen Research & Development. Dr. Burke disclosed consultancy fees from Janssen and others. Dr. Galardy is an equity holder in Abbott and AbbVie.

Adding ibrutinib to chemotherapy did not improve outcomes for children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL), an interim analysis of the SPARKLE trial showed.

Among 51 patients aged 1-30 years with mature B-NHL that had been diagnosed before age 18, there was no significant difference in the primary endpoint of event-free survival (EFS) between patients assigned on a 2:1 basis to receive either ibrutinib (Imbruvica) plus one of two chemotherapy regimens or to chemotherapy alone. In fact, EFS was shorter among patients assigned to ibrutinib, although a larger proportion of these patients had previously received rituximab, a known factor for poor prognosis, reported Amos Burke, MD, from Cambridge (England) University.

The trial was stopped for futility in May 2020, after a median follow-up of 17.97 months.

“Further studies are required to determine the optimal therapy for patients with relapsed, mature B-NHL, especially those who have received prior rituximab,” he said in an audio walk-through of a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a very challenging patient population because they historically have had a very poor survival rate,” commented Paul J. Galardy, MD, a pediatric hematologist/oncologist at the Mayo Clinic in Rochester, Minn., who was not involved in the study.

“The field has struggled to improve outcomes for these patients in part because there are relatively few patients per year with relapsed refractory mature B-cell lymphoma due to the very effective nature of the up-front therapy. This makes new clinical trials difficult to perform,” he said.
 

Poor prognosis

Ibrutinib, an inhibitor of Bruton tyrosine kinase, is approved in the United States for treatment of marginal zone lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, as well as other indications, all in adults only. It has also been shown to have activity against B-NHL in preclinical and early human trials, Dr. Burke said.

Given the poor prognosis of children and young adults with relapsed/refractory mature B-NHL – a 2-year overall survival (OS) of 30% or less with chemoimmunotherapy – the investigators tested whether adding ibrutinib to the standard of care could improve outcomes.

They enrolled patients with relapsed/refractory B-NHL in first relapse or primarily refractory to conventional therapy, with measurable disease (greater than 1 cm) by CT, bone marrow involvement, or cerebrospinal fluid with blasts. The patients were required to have Karnofsky-Lansky performance scores of 50 or greater.

The histologies included Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt-like lymphoma, Burkitt leukemia, primary mediastinal B-cell lymphoma, and other unspecified types.

Dr. Burke reported results on 48 patients included in the May 2020 analysis, plus 3 additional patients who were enrolled between the data cutoff for the first analysis and the meeting of the independent data monitoring committee where the decision was made to stop the trial.

A total of 35 patients were randomized to receive ibrutinib with either the RICE (rituximab plus ifosfamide, carboplatin, and etoposide) or RVICI (rituximab plus vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone) regimen. All of these patients received treatment on study.

Of the 18 patients randomized to receive either RICE or RVICI alone, 1 did not receive any cycles of chemoimmunotherapy.

At the data cutoff for the updated analysis in November 2020, 14 patients assigned to ibrutinib and 4 assigned to chemoimmunotherapy alone remained on study; no patients in either arm were still receiving therapy.

A total of 17 patients assigned to the combination arm died and 4 withdrew consent. In the chemoimmunotherapy-alone arm, 10 died and 2 withdrew consent.

In both arms, patients were treated until either completing three cycles of therapy, start of conditioning treatment prior to stem cell transplantation, disease progression, or unacceptable toxicity.

In the ibrutinib arm, the median EFS was 5.36 months, compared with 6.97 months with chemoimmunotherapy alone, translating into a hazard ratio for EFS with ibrutinib of 1.078 (nonsignificant).

The respective median overall survival was 13.44 versus 11.07 months,

Subgroup analysis showed that EFS and OS did not differ significantly by age, histology, background regimen, or central nervous system or bone marrow involvement. ­

Overall response rates were 68.6% in the ibrutinib arm, and 81.3% in the chemoimmunotherapy arm. The respective complete response rates were 8.6% and 18.8%, and partial response rates were 60% and 62.5%.

The overall treatment-emergent adverse event (TEAE) profile was similar between the treatment arms, although six patients in the ibrutinib arm versus one in the chemoimmunotherapy arm experienced a major hemorrhage. One patients in the ibrutinib arm died from pulmonary hemorrhage.

Dr. Burke noted that, although the numbers were small, the failure to see a difference in efficacy between study arms may have been caused in part by a greater number of patients assigned to ibrutinib who had received prior treatment with rituximab (85.7% vs. 56.3%).
 

Not the right partner?

“The results of this study would suggest that ibrutinib is not the right agent. This is not altogether unexpected,” Dr. Galardy said. “The benefit of ibrutinib in adults with mature B-cell lymphoma is primarily based on biological characteristics of lymphomas that develop in older individuals.”

He noted that mature B-cell lymphoma in older adults is often of the activated B-cell subtype, which frequently has mutations that make it sensitive to ibrutinib. In contrast, children, adolescents, and young adults more commonly have the germinal center B-cell subtype that doesn’t have similarly targetable mutations.

He added that, although the reasons for poor prognosis in patients with prior rituximab exposure are unclear, “it is likely that patients who have recurrent or refractory disease after therapy that included rituximab may have developed resistance to this drug. Since both arms of this study included rituximab as a component of the therapy, the patients with prior exposure to this drug may have had reduced benefit of the additional rituximab, compared with those who had not received the drug before.”

The SPARKLE trial was funded by Janssen Research & Development. Dr. Burke disclosed consultancy fees from Janssen and others. Dr. Galardy is an equity holder in Abbott and AbbVie.

The Food and Drug Administration granted an accelerated approval April 24, 2021, for a new drug for use in patients with relapsed/refractory diffuse large B-cell lymphomas (DLBCL) who have tried at least two prior systemic therapies.

The new product, loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics), is the first and only CD19-targeted antibody-drug conjugate approved for this disease.

DLBCL is the most common type of non-Hodgkin lymphoma in the United States, but the indication also includes DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.

“There is a significant unmet need for treatment options for patients with [relapsed or refractory] DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,” Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, said in a company press release.

The company also cited data from previous clinical trials showing that more than 40% of first-line DLBCL treatments fail, and that these patients have a poor prognosis, worsening with each line of therapy that is tried.
 

Accelerated approval based on ORR

The accelerated approval was based on overall response rate data from the single-arm LOTIS-2 trial. All patients received the new drug, administered as a 30-minute infusion once every 3 weeks for 1 year.

The trial was conducted in 145 patients with relapsed/refractory DLBCL who had already tried at least two lines of systemic therapy. Dr. Caimi noted that this included patients who had been heavily pretreated, as the population included patients who previously received stem cell transplant or chimeric antigen receptor T-cell therapy.

The ORR was 48.3% (70/145 patients), which included a complete response rate of 24.1% (35/145 patients) and a partial response rate of 24.1% (35/145 patients).

Patients had a median time to response of 1.3 months and the median duration of response for the 70 responders was 10.3 months.

“Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial,” the company noted.

A phase 3 confirmatory is underway: the LOTIS 5 trial (NCT04384484) compares the combination of loncastuximab tesirine and rituximab versus chemoimmunotherapy in patients with relapsed/refractory DLBCL.

The company also noted that in a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, an increase in levels of the liver enzyme gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

In the LOTIS-2 trial, the most common (≥10%) grade 3 or higher treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), GGT increase (17.2%) and anemia (10.3%).

Permanent treatment discontinuation as the result of an adverse reaction occurred in 19% of patients, and these included a GGT increase, edema, and effusion.

Dose reductions because of an adverse reaction occurred in 8% of patients, and most were the result of a GGT increase. Dosage interruptions because of an adverse reaction occurred in 49% of patients, and these included a GGT increase, neutropenia, thrombocytopenia, and edema.
 

Warnings on effusions, infections, and skin reactions

The product carries a warning that serious effusion and edema has been reported. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites), grade 3 pleural effusion occurred in 3%, and grade 3 or 4 pericardial effusion occurred in 1%.

Prescribers are recommended to monitor patients for new or worsening edema or effusions, and to consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating.

The product also carries a warning about fatal and serious infections, including opportunistic infections, and serious cutaneous reactions, including photosensitivity reaction, rash (including exfoliative and maculopapular), and erythema.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration granted an accelerated approval April 24, 2021, for a new drug for use in patients with relapsed/refractory diffuse large B-cell lymphomas (DLBCL) who have tried at least two prior systemic therapies.

The new product, loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics), is the first and only CD19-targeted antibody-drug conjugate approved for this disease.

DLBCL is the most common type of non-Hodgkin lymphoma in the United States, but the indication also includes DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.

“There is a significant unmet need for treatment options for patients with [relapsed or refractory] DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,” Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, said in a company press release.

The company also cited data from previous clinical trials showing that more than 40% of first-line DLBCL treatments fail, and that these patients have a poor prognosis, worsening with each line of therapy that is tried.
 

Accelerated approval based on ORR

The accelerated approval was based on overall response rate data from the single-arm LOTIS-2 trial. All patients received the new drug, administered as a 30-minute infusion once every 3 weeks for 1 year.

The trial was conducted in 145 patients with relapsed/refractory DLBCL who had already tried at least two lines of systemic therapy. Dr. Caimi noted that this included patients who had been heavily pretreated, as the population included patients who previously received stem cell transplant or chimeric antigen receptor T-cell therapy.

The ORR was 48.3% (70/145 patients), which included a complete response rate of 24.1% (35/145 patients) and a partial response rate of 24.1% (35/145 patients).

Patients had a median time to response of 1.3 months and the median duration of response for the 70 responders was 10.3 months.

“Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial,” the company noted.

A phase 3 confirmatory is underway: the LOTIS 5 trial (NCT04384484) compares the combination of loncastuximab tesirine and rituximab versus chemoimmunotherapy in patients with relapsed/refractory DLBCL.

The company also noted that in a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, an increase in levels of the liver enzyme gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

In the LOTIS-2 trial, the most common (≥10%) grade 3 or higher treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), GGT increase (17.2%) and anemia (10.3%).

Permanent treatment discontinuation as the result of an adverse reaction occurred in 19% of patients, and these included a GGT increase, edema, and effusion.

Dose reductions because of an adverse reaction occurred in 8% of patients, and most were the result of a GGT increase. Dosage interruptions because of an adverse reaction occurred in 49% of patients, and these included a GGT increase, neutropenia, thrombocytopenia, and edema.
 

Warnings on effusions, infections, and skin reactions

The product carries a warning that serious effusion and edema has been reported. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites), grade 3 pleural effusion occurred in 3%, and grade 3 or 4 pericardial effusion occurred in 1%.

Prescribers are recommended to monitor patients for new or worsening edema or effusions, and to consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating.

The product also carries a warning about fatal and serious infections, including opportunistic infections, and serious cutaneous reactions, including photosensitivity reaction, rash (including exfoliative and maculopapular), and erythema.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration granted an accelerated approval April 24, 2021, for a new drug for use in patients with relapsed/refractory diffuse large B-cell lymphomas (DLBCL) who have tried at least two prior systemic therapies.

The new product, loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics), is the first and only CD19-targeted antibody-drug conjugate approved for this disease.

DLBCL is the most common type of non-Hodgkin lymphoma in the United States, but the indication also includes DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.

“There is a significant unmet need for treatment options for patients with [relapsed or refractory] DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,” Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, said in a company press release.

The company also cited data from previous clinical trials showing that more than 40% of first-line DLBCL treatments fail, and that these patients have a poor prognosis, worsening with each line of therapy that is tried.
 

Accelerated approval based on ORR

The accelerated approval was based on overall response rate data from the single-arm LOTIS-2 trial. All patients received the new drug, administered as a 30-minute infusion once every 3 weeks for 1 year.

The trial was conducted in 145 patients with relapsed/refractory DLBCL who had already tried at least two lines of systemic therapy. Dr. Caimi noted that this included patients who had been heavily pretreated, as the population included patients who previously received stem cell transplant or chimeric antigen receptor T-cell therapy.

The ORR was 48.3% (70/145 patients), which included a complete response rate of 24.1% (35/145 patients) and a partial response rate of 24.1% (35/145 patients).

Patients had a median time to response of 1.3 months and the median duration of response for the 70 responders was 10.3 months.

“Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial,” the company noted.

A phase 3 confirmatory is underway: the LOTIS 5 trial (NCT04384484) compares the combination of loncastuximab tesirine and rituximab versus chemoimmunotherapy in patients with relapsed/refractory DLBCL.

The company also noted that in a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, an increase in levels of the liver enzyme gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

In the LOTIS-2 trial, the most common (≥10%) grade 3 or higher treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), GGT increase (17.2%) and anemia (10.3%).

Permanent treatment discontinuation as the result of an adverse reaction occurred in 19% of patients, and these included a GGT increase, edema, and effusion.

Dose reductions because of an adverse reaction occurred in 8% of patients, and most were the result of a GGT increase. Dosage interruptions because of an adverse reaction occurred in 49% of patients, and these included a GGT increase, neutropenia, thrombocytopenia, and edema.
 

Warnings on effusions, infections, and skin reactions

The product carries a warning that serious effusion and edema has been reported. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites), grade 3 pleural effusion occurred in 3%, and grade 3 or 4 pericardial effusion occurred in 1%.

Prescribers are recommended to monitor patients for new or worsening edema or effusions, and to consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating.

The product also carries a warning about fatal and serious infections, including opportunistic infections, and serious cutaneous reactions, including photosensitivity reaction, rash (including exfoliative and maculopapular), and erythema.

A version of this article first appeared on Medscape.com.

A dose-adjusted R-CHOP may be the best treatment for elderly patients with diffuse large beta-cell lymphoma (DLBCL), according to a review of 38 studies that examined this aged population.

Nephron/Wikimedia Commons/CC BY-SA 3.0

In addition, treatment choices based on new tools such as the Comprehensive Geriatric Assessment appeared to provide useful guidance based on the comorbidities and frailty index of this group of patients, according to Alda Tavares, MD, of Hospital Pedro Hispano, Matosinhos (Portugal) Local Health Unit, and Ilídia Moreira, MD, of the Portuguese Institute of Oncology of Porto.
 

Study characteristics

Of the 38 studies assessed, 13 were retrospective and 25 were phase II/III clinical trials. Most of these studies investigated the efficacy of dose-adjusted R-CHOP regimen, according to the review published online in Critical Reviews in Oncology/Hematology.

Alternative therapeutic drugs as well as the use of geriatric assessment were also investigated.

In terms of the elderly populations assessed, 11 out of 38 studies included at least 30 patients over age 80 years, although 11 other studies did not specify the number of patients older than 80 years. Eight of the studies included exclusively patients aged 80 years and over. Three of these studies were phase II trials.

Only six of the clinical trials required a geriatric assessment tool for inclusion criteria or therapeutic regime choice, using the Cumulative Illness Rating Scale–Geriatric (CIRS-G), the performance in activities of daily living (ADL) and/or instrumental activities of daily living (IADL) tools.

Most of the studies investigated the efficacy of R-CHOP regimen at different doses and variations, with 11 studies using alternative anthracycline in place of doxorubicin.
 

MiniCHOP mattered

Elderly patients over 80 years achieved complete response (CR) rates from 37.2% to 66.7% and 2-year overall survival (OS) from 31.9% to 64.7% across the studies reviewed. Overall, for fit patients aged 80 and over, the strongest evidence favored the use of an R-miniCHOP regimen, according to the authors.

In the 25 studies with treatment based on R-CHOP/modified R-CHOP or immunochemotherapy with an alternative anthracycline, the CR rate was below 50% in three studies and over 60% in the majority. Higher CR rates of 71%-88.9% were achieved in eight studies.

For patients over 80 years, the strongest evidence favored rituximab/ofatumumab-miniCHOP, based on two studies. In both studies, patients over 80 years old, without significant comorbidities, received CHOP regime with a dose reduction of about 50% (miniCHOP: cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and 1 mg vincristine on day 1 of each cycle, and prednisone 40 mg/m² on days 1-5) plus an anti–CD-20 antibody (rituximab 375 mg/m² or ofatumumab 1,000 mg). The first of these studies obtained CR rate of 62% and 2-year OS of 59% with low toxicities. The second study achieved slightly better results, according to the reviewers, who suggested the difference was possibly because of a prephase treatment and/or the use of ofatumumab.

One study group developed a simple prognostic model based on multivariate analysis of 108 patients aged 80 years and older treated in their study with R-CHOP at full (48%) or reduced dose (51%). Patients with at least two out of three risk factors (age > 85 years, revised International Prognostic Index score 3-5 and CIRS > 5) had worse survival than did those with 0-1 risk factors, with a median OS of 12 months vs. 45 months, P = .001, respectively).

“All these studies results favor the tailored treatment approach,” the reviewers stated. “More prospective studies are still needed to demonstrate and validate the adequate tools for the selection of patients and their optimal treatment. They would provide the grounds for clinical therapeutic decision, aiming for tailored treatment and fulfilling best individual expectations and outcome,” they concluded.

The authors reported that they received no research funds for the study and that they had no disclosures.
 

[email protected]

A dose-adjusted R-CHOP may be the best treatment for elderly patients with diffuse large beta-cell lymphoma (DLBCL), according to a review of 38 studies that examined this aged population.

Nephron/Wikimedia Commons/CC BY-SA 3.0

In addition, treatment choices based on new tools such as the Comprehensive Geriatric Assessment appeared to provide useful guidance based on the comorbidities and frailty index of this group of patients, according to Alda Tavares, MD, of Hospital Pedro Hispano, Matosinhos (Portugal) Local Health Unit, and Ilídia Moreira, MD, of the Portuguese Institute of Oncology of Porto.
 

Study characteristics

Of the 38 studies assessed, 13 were retrospective and 25 were phase II/III clinical trials. Most of these studies investigated the efficacy of dose-adjusted R-CHOP regimen, according to the review published online in Critical Reviews in Oncology/Hematology.

Alternative therapeutic drugs as well as the use of geriatric assessment were also investigated.

In terms of the elderly populations assessed, 11 out of 38 studies included at least 30 patients over age 80 years, although 11 other studies did not specify the number of patients older than 80 years. Eight of the studies included exclusively patients aged 80 years and over. Three of these studies were phase II trials.

Only six of the clinical trials required a geriatric assessment tool for inclusion criteria or therapeutic regime choice, using the Cumulative Illness Rating Scale–Geriatric (CIRS-G), the performance in activities of daily living (ADL) and/or instrumental activities of daily living (IADL) tools.

Most of the studies investigated the efficacy of R-CHOP regimen at different doses and variations, with 11 studies using alternative anthracycline in place of doxorubicin.
 

MiniCHOP mattered

Elderly patients over 80 years achieved complete response (CR) rates from 37.2% to 66.7% and 2-year overall survival (OS) from 31.9% to 64.7% across the studies reviewed. Overall, for fit patients aged 80 and over, the strongest evidence favored the use of an R-miniCHOP regimen, according to the authors.

In the 25 studies with treatment based on R-CHOP/modified R-CHOP or immunochemotherapy with an alternative anthracycline, the CR rate was below 50% in three studies and over 60% in the majority. Higher CR rates of 71%-88.9% were achieved in eight studies.

For patients over 80 years, the strongest evidence favored rituximab/ofatumumab-miniCHOP, based on two studies. In both studies, patients over 80 years old, without significant comorbidities, received CHOP regime with a dose reduction of about 50% (miniCHOP: cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and 1 mg vincristine on day 1 of each cycle, and prednisone 40 mg/m² on days 1-5) plus an anti–CD-20 antibody (rituximab 375 mg/m² or ofatumumab 1,000 mg). The first of these studies obtained CR rate of 62% and 2-year OS of 59% with low toxicities. The second study achieved slightly better results, according to the reviewers, who suggested the difference was possibly because of a prephase treatment and/or the use of ofatumumab.

One study group developed a simple prognostic model based on multivariate analysis of 108 patients aged 80 years and older treated in their study with R-CHOP at full (48%) or reduced dose (51%). Patients with at least two out of three risk factors (age > 85 years, revised International Prognostic Index score 3-5 and CIRS > 5) had worse survival than did those with 0-1 risk factors, with a median OS of 12 months vs. 45 months, P = .001, respectively).

“All these studies results favor the tailored treatment approach,” the reviewers stated. “More prospective studies are still needed to demonstrate and validate the adequate tools for the selection of patients and their optimal treatment. They would provide the grounds for clinical therapeutic decision, aiming for tailored treatment and fulfilling best individual expectations and outcome,” they concluded.

The authors reported that they received no research funds for the study and that they had no disclosures.
 

[email protected]

A dose-adjusted R-CHOP may be the best treatment for elderly patients with diffuse large beta-cell lymphoma (DLBCL), according to a review of 38 studies that examined this aged population.

Nephron/Wikimedia Commons/CC BY-SA 3.0

In addition, treatment choices based on new tools such as the Comprehensive Geriatric Assessment appeared to provide useful guidance based on the comorbidities and frailty index of this group of patients, according to Alda Tavares, MD, of Hospital Pedro Hispano, Matosinhos (Portugal) Local Health Unit, and Ilídia Moreira, MD, of the Portuguese Institute of Oncology of Porto.
 

Study characteristics

Of the 38 studies assessed, 13 were retrospective and 25 were phase II/III clinical trials. Most of these studies investigated the efficacy of dose-adjusted R-CHOP regimen, according to the review published online in Critical Reviews in Oncology/Hematology.

Alternative therapeutic drugs as well as the use of geriatric assessment were also investigated.

In terms of the elderly populations assessed, 11 out of 38 studies included at least 30 patients over age 80 years, although 11 other studies did not specify the number of patients older than 80 years. Eight of the studies included exclusively patients aged 80 years and over. Three of these studies were phase II trials.

Only six of the clinical trials required a geriatric assessment tool for inclusion criteria or therapeutic regime choice, using the Cumulative Illness Rating Scale–Geriatric (CIRS-G), the performance in activities of daily living (ADL) and/or instrumental activities of daily living (IADL) tools.

Most of the studies investigated the efficacy of R-CHOP regimen at different doses and variations, with 11 studies using alternative anthracycline in place of doxorubicin.
 

MiniCHOP mattered

Elderly patients over 80 years achieved complete response (CR) rates from 37.2% to 66.7% and 2-year overall survival (OS) from 31.9% to 64.7% across the studies reviewed. Overall, for fit patients aged 80 and over, the strongest evidence favored the use of an R-miniCHOP regimen, according to the authors.

In the 25 studies with treatment based on R-CHOP/modified R-CHOP or immunochemotherapy with an alternative anthracycline, the CR rate was below 50% in three studies and over 60% in the majority. Higher CR rates of 71%-88.9% were achieved in eight studies.

For patients over 80 years, the strongest evidence favored rituximab/ofatumumab-miniCHOP, based on two studies. In both studies, patients over 80 years old, without significant comorbidities, received CHOP regime with a dose reduction of about 50% (miniCHOP: cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and 1 mg vincristine on day 1 of each cycle, and prednisone 40 mg/m² on days 1-5) plus an anti–CD-20 antibody (rituximab 375 mg/m² or ofatumumab 1,000 mg). The first of these studies obtained CR rate of 62% and 2-year OS of 59% with low toxicities. The second study achieved slightly better results, according to the reviewers, who suggested the difference was possibly because of a prephase treatment and/or the use of ofatumumab.

One study group developed a simple prognostic model based on multivariate analysis of 108 patients aged 80 years and older treated in their study with R-CHOP at full (48%) or reduced dose (51%). Patients with at least two out of three risk factors (age > 85 years, revised International Prognostic Index score 3-5 and CIRS > 5) had worse survival than did those with 0-1 risk factors, with a median OS of 12 months vs. 45 months, P = .001, respectively).

“All these studies results favor the tailored treatment approach,” the reviewers stated. “More prospective studies are still needed to demonstrate and validate the adequate tools for the selection of patients and their optimal treatment. They would provide the grounds for clinical therapeutic decision, aiming for tailored treatment and fulfilling best individual expectations and outcome,” they concluded.

The authors reported that they received no research funds for the study and that they had no disclosures.
 

[email protected]

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

After 10 years of follow-up, event-free survival and overall survival were similar between conventional chemotherapy treated patients with aggressive B-cell lymphoma and those receiving high-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation (HSCT), according to a report published online in the Lancet Hematology.

Michael Bonert/WikimediaCommons/CC BY-SA 3.0

The open-label, randomized, phase 3 trial (NCT00129090) was conducted across 61 centers in Germany on patients aged 18-60 years who had newly diagnosed, high-risk, aggressive B-cell lymphoma, according to Fabian Frontzek, MD, of the University Hospital Münster (Germany) and colleagues.

Between March 2003 and April 2009, patients were randomly assigned to eight cycles of conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The intention-to-treat population comprised 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group. The median follow-up was 9.3 years.
 

Similar outcomes

The 10-year event-free survival was 51% in the R-MegaCHOEP group and 57% in the R-CHOEP-14 group, a nonsignificant difference (P = .23). Similarly, the 10-year progression-free survival was 59% in the

R-MegaCHOEP group and 60% (P = .64). The 10-year overall survival was 66% in the R-MegaCHOEP group and 72% in the R-CHOEP-14 group (P = .26). Among the 190 patients who had complete remission or unconfirmed complete remission, relapse occurred in 30 (16%); 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group.

In terms of secondary malignancies, 22 were reported in the intention-to-treat population; comprising 12 (9%) of 127 patients in the R-CHOEP-14 group and 10 (8%) of 126 patients in the R-MegaCHOEP group.

Patients who relapsed with aggressive histology and with CNS involvement in particular had worse outcomes and “represent a group with an unmet medical need, for which new molecular and cellular therapies should be studied,” the authors stated.

“This study shows that, in the rituximab era, high-dose therapy and autologous HSCT in first-line treatment does not improve long-term survival of younger high-risk patients with aggressive B-cell lymphoma. The R-CHOEP-14 regimen led to favorable outcomes, supporting its continued use in such patients,” the researchers concluded.

In an accompanying commentary, Gita Thanarajasingam, MD, of the Mayo Clinic, Rochester, Minn., and colleagues added that the issue of long-term outcomes is critical to evaluating these new regimens.

They applauded the inclusion of secondary malignancies in the long-term follow-up, but regretted the lack of the, admittedly resource-intensive, information on long-term nonneoplastic adverse events. They added that “the burden of late adverse events such as cardiotoxicity, cumulative neuropathy, delayed infections, or lasting cognitive effects, among others that might drive substantial morbidity, does matter to lymphoma survivors.”

They also commented on the importance of considering effects on fertility in these patients, noting that R-MegaCHOEP patients would be unable to conceive naturally, but that the effect of R-CHOEP-14 was less clear.

“We encourage ongoing emphasis on this type of longitudinal follow-up of secondary malignancies and other nonneoplastic late toxicities in phase 3 studies as well as in the real world in hematological malignancies, so that after prioritizing cure in the front-line setting, we do not neglect the life we have helped survivors achieve for years and decades to come,” they concluded.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. The authors reported grants, personal fees, and non-financial support from multiple pharmaceutical and biotechnology companies. Dr. Thanarajasingam and her colleagues reported that they had no competing interests.

[email protected]

After 10 years of follow-up, event-free survival and overall survival were similar between conventional chemotherapy treated patients with aggressive B-cell lymphoma and those receiving high-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation (HSCT), according to a report published online in the Lancet Hematology.

Michael Bonert/WikimediaCommons/CC BY-SA 3.0

The open-label, randomized, phase 3 trial (NCT00129090) was conducted across 61 centers in Germany on patients aged 18-60 years who had newly diagnosed, high-risk, aggressive B-cell lymphoma, according to Fabian Frontzek, MD, of the University Hospital Münster (Germany) and colleagues.

Between March 2003 and April 2009, patients were randomly assigned to eight cycles of conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The intention-to-treat population comprised 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group. The median follow-up was 9.3 years.
 

Similar outcomes

The 10-year event-free survival was 51% in the R-MegaCHOEP group and 57% in the R-CHOEP-14 group, a nonsignificant difference (P = .23). Similarly, the 10-year progression-free survival was 59% in the

R-MegaCHOEP group and 60% (P = .64). The 10-year overall survival was 66% in the R-MegaCHOEP group and 72% in the R-CHOEP-14 group (P = .26). Among the 190 patients who had complete remission or unconfirmed complete remission, relapse occurred in 30 (16%); 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group.

In terms of secondary malignancies, 22 were reported in the intention-to-treat population; comprising 12 (9%) of 127 patients in the R-CHOEP-14 group and 10 (8%) of 126 patients in the R-MegaCHOEP group.

Patients who relapsed with aggressive histology and with CNS involvement in particular had worse outcomes and “represent a group with an unmet medical need, for which new molecular and cellular therapies should be studied,” the authors stated.

“This study shows that, in the rituximab era, high-dose therapy and autologous HSCT in first-line treatment does not improve long-term survival of younger high-risk patients with aggressive B-cell lymphoma. The R-CHOEP-14 regimen led to favorable outcomes, supporting its continued use in such patients,” the researchers concluded.

In an accompanying commentary, Gita Thanarajasingam, MD, of the Mayo Clinic, Rochester, Minn., and colleagues added that the issue of long-term outcomes is critical to evaluating these new regimens.

They applauded the inclusion of secondary malignancies in the long-term follow-up, but regretted the lack of the, admittedly resource-intensive, information on long-term nonneoplastic adverse events. They added that “the burden of late adverse events such as cardiotoxicity, cumulative neuropathy, delayed infections, or lasting cognitive effects, among others that might drive substantial morbidity, does matter to lymphoma survivors.”

They also commented on the importance of considering effects on fertility in these patients, noting that R-MegaCHOEP patients would be unable to conceive naturally, but that the effect of R-CHOEP-14 was less clear.

“We encourage ongoing emphasis on this type of longitudinal follow-up of secondary malignancies and other nonneoplastic late toxicities in phase 3 studies as well as in the real world in hematological malignancies, so that after prioritizing cure in the front-line setting, we do not neglect the life we have helped survivors achieve for years and decades to come,” they concluded.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. The authors reported grants, personal fees, and non-financial support from multiple pharmaceutical and biotechnology companies. Dr. Thanarajasingam and her colleagues reported that they had no competing interests.

[email protected]

After 10 years of follow-up, event-free survival and overall survival were similar between conventional chemotherapy treated patients with aggressive B-cell lymphoma and those receiving high-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation (HSCT), according to a report published online in the Lancet Hematology.

Michael Bonert/WikimediaCommons/CC BY-SA 3.0

The open-label, randomized, phase 3 trial (NCT00129090) was conducted across 61 centers in Germany on patients aged 18-60 years who had newly diagnosed, high-risk, aggressive B-cell lymphoma, according to Fabian Frontzek, MD, of the University Hospital Münster (Germany) and colleagues.

Between March 2003 and April 2009, patients were randomly assigned to eight cycles of conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The intention-to-treat population comprised 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group. The median follow-up was 9.3 years.
 

Similar outcomes

The 10-year event-free survival was 51% in the R-MegaCHOEP group and 57% in the R-CHOEP-14 group, a nonsignificant difference (P = .23). Similarly, the 10-year progression-free survival was 59% in the

R-MegaCHOEP group and 60% (P = .64). The 10-year overall survival was 66% in the R-MegaCHOEP group and 72% in the R-CHOEP-14 group (P = .26). Among the 190 patients who had complete remission or unconfirmed complete remission, relapse occurred in 30 (16%); 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group.

In terms of secondary malignancies, 22 were reported in the intention-to-treat population; comprising 12 (9%) of 127 patients in the R-CHOEP-14 group and 10 (8%) of 126 patients in the R-MegaCHOEP group.

Patients who relapsed with aggressive histology and with CNS involvement in particular had worse outcomes and “represent a group with an unmet medical need, for which new molecular and cellular therapies should be studied,” the authors stated.

“This study shows that, in the rituximab era, high-dose therapy and autologous HSCT in first-line treatment does not improve long-term survival of younger high-risk patients with aggressive B-cell lymphoma. The R-CHOEP-14 regimen led to favorable outcomes, supporting its continued use in such patients,” the researchers concluded.

In an accompanying commentary, Gita Thanarajasingam, MD, of the Mayo Clinic, Rochester, Minn., and colleagues added that the issue of long-term outcomes is critical to evaluating these new regimens.

They applauded the inclusion of secondary malignancies in the long-term follow-up, but regretted the lack of the, admittedly resource-intensive, information on long-term nonneoplastic adverse events. They added that “the burden of late adverse events such as cardiotoxicity, cumulative neuropathy, delayed infections, or lasting cognitive effects, among others that might drive substantial morbidity, does matter to lymphoma survivors.”

They also commented on the importance of considering effects on fertility in these patients, noting that R-MegaCHOEP patients would be unable to conceive naturally, but that the effect of R-CHOEP-14 was less clear.

“We encourage ongoing emphasis on this type of longitudinal follow-up of secondary malignancies and other nonneoplastic late toxicities in phase 3 studies as well as in the real world in hematological malignancies, so that after prioritizing cure in the front-line setting, we do not neglect the life we have helped survivors achieve for years and decades to come,” they concluded.

The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. The authors reported grants, personal fees, and non-financial support from multiple pharmaceutical and biotechnology companies. Dr. Thanarajasingam and her colleagues reported that they had no competing interests.

[email protected]

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A novel T-cell engineered product, Orca-T (Orca Bio), was associated with lower incidence of both acute and chronic graft-versus-host disease (GVHD) and more than double the rate of GVHD-free and relapse-free survival, compared with the current standard of care for patients undergoing hematopoietic stem cell transplants (HSCT), investigators said.

In both a multicenter phase 1 trial (NCT04013685) and single-center phase 1/2 trial (NCT01660607) with a total of 50 patients, those who received Orca-T with single-agent GVHD prophylaxis had a 1-year GVHD-free and relapse-free survival rate of 75%, compared with 31% for patients who received standard of care with two-agent prophylaxis, reported Everett H. Meyer, MD, PhD, from the Stanford (Calif.) University.

“Orca-T has good evidence for reduced acute graft-versus-host disease, reduced chromic graft-versus-host disease, and a low nonrelapse mortality,” he said at the Transplant & Cellular Therapies Meetings.

The product can be quickly manufactured and delivered to treatment centers across the continental United States, with “vein-to-vein” time of less than 72 hours, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Orca-T consists of highly purified, donor-derived T-regulatory (Treg) cells that are sorted and delivered on day 0 with hematopoietic stem cells, without immunosuppressants, followed 2 days later with infusion of a matching dose of conventional T cells.

“The Treg cells are allowed to expand to create the right microenvironment for the [conventional T cells],” he explained.

In preclinical studies, donor-derived, high-purity Tregs delivered prior to adoptive transfer of conventional T cells prevented GVHD while maintaining graft-versus-tumor immunity, he said.
 

Two T-cell infusions

He reported updated results from current studies on a total of 50 adults, with a cohort of 144 patients treated concurrently with standard of care as controls.

The Orca-T–treated patients had a median age of 47 and 52% were male. Indications for transplant included acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia, B-cell lymphoma, myelodysplastic syndrome/myelofibrosis, and other unspecified indications.

In both the Orca-T and control cohorts, patients underwent myeloablative conditioning from 10 to 2 days prior to stem cell infusion.

As noted patients in the experimental arm received infusion of hematopoietic stem/progenitor cells and Tregs, followed 2 days later by conventional T-cell infusion, and, on the day after that, tacrolimus at a target dose of 4.6 ng/mL. The conventional T cells were reserved from donor apheresis and were otherwise unmanipulated prior to infusion into the recipient, Dr. Meyer noted.

Patients in the standard-of-care arm received tacrolimus on the day before standard infusion of the apheresis product, followed by methotrexate prophylaxis on days 1, 3, 6 and 11.

Time to neutrophil engraftment, platelet engraftment, and from day 0 to hospital discharge were all significantly shorter in the Orca-T group, at 12 versus 14 days (P < .0001), 11 vs. 17 days (P < .0001), and 15 vs. 17 days (P = .01) respectively.

At 100 days of follow-up, the rate of grade 2 or greater acute GVHD was 30% among standard-of-care patients versus 10% among Orca-T–treated patients. At 1-year follow-up, respective rates of chronic GVHD were 46% vs. 3%.
 

Safety

“In general, the protocol is extremely well tolerated by our patients. We’ve seen no exceptional infectious disease complications, and we’ve seen no other major complications,” Dr. Meyer said.

Cytomegalovirus prophylaxis was used variably, depending on the center and on the attending physician. Epstein-Barr virus reactivation occurred in eight patients, with one requiring therapy, but there was no biopsy or radiographic evidence of posttransplant lymphoproliferative disorder.

In all, 18% of patients had serious adverse events during the reporting period, all of which resolved. There were no treatment-related deaths in the Orca-T arm, compared with 11% of controls.
 

Engraftment differences explored

In the question-and-answer session following the presentation, Christopher J. Gamper, MD, PhD, from the Johns Hopkins Hospital in Baltimore, told Dr. Meyer that “your outcomes from Orca-T look excellent,” and asked about the cost differential, compared with similar, unmanipulated transplants performed with standard GVHD prophylaxis.

“Is this recovered by lower costs for treatment of GVHD?” he asked.

“I have not done an economic cost analysis of course, and I think others may be looking into this,” Dr. Meyer replied. “Graft engineering can be expensive, although it’s an engineering proposition and one could imagine that the costs will go down substantially over time.”

Session moderator Alan Hanash, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York, commented on the differences in engraftment between the experimental controls arms, and asked Dr. Meyer: “Do you think this is due to the difference in prophylaxis? Absence of methotrexate? Do you think that it could be a direct impact of regulatory T cells on hematopoietic engraftment?”

“Certainly not having methotrexate is beneficial for engraftment, and may account for the differences we see, Dr. Meyer said. “However, it is possible that Tregs could be playing a facilitative role. There certainly is good preclinical literature that Tregs, particularly in the bone marrow space, can facilitate bone marrow engraftment.”

The Orca-T trials are sponsored by Orca Bio and Stanford, with support from the National Institutes of Health. Dr. Meyer receives research support from Orca and is a scientific adviser to GigaGen, Triursus, Incyte, and Indee Labs. Dr. Hanash and Dr. Gamper had no relevant disclosures.

A novel T-cell engineered product, Orca-T (Orca Bio), was associated with lower incidence of both acute and chronic graft-versus-host disease (GVHD) and more than double the rate of GVHD-free and relapse-free survival, compared with the current standard of care for patients undergoing hematopoietic stem cell transplants (HSCT), investigators said.

In both a multicenter phase 1 trial (NCT04013685) and single-center phase 1/2 trial (NCT01660607) with a total of 50 patients, those who received Orca-T with single-agent GVHD prophylaxis had a 1-year GVHD-free and relapse-free survival rate of 75%, compared with 31% for patients who received standard of care with two-agent prophylaxis, reported Everett H. Meyer, MD, PhD, from the Stanford (Calif.) University.

“Orca-T has good evidence for reduced acute graft-versus-host disease, reduced chromic graft-versus-host disease, and a low nonrelapse mortality,” he said at the Transplant & Cellular Therapies Meetings.

The product can be quickly manufactured and delivered to treatment centers across the continental United States, with “vein-to-vein” time of less than 72 hours, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Orca-T consists of highly purified, donor-derived T-regulatory (Treg) cells that are sorted and delivered on day 0 with hematopoietic stem cells, without immunosuppressants, followed 2 days later with infusion of a matching dose of conventional T cells.

“The Treg cells are allowed to expand to create the right microenvironment for the [conventional T cells],” he explained.

In preclinical studies, donor-derived, high-purity Tregs delivered prior to adoptive transfer of conventional T cells prevented GVHD while maintaining graft-versus-tumor immunity, he said.
 

Two T-cell infusions

He reported updated results from current studies on a total of 50 adults, with a cohort of 144 patients treated concurrently with standard of care as controls.

The Orca-T–treated patients had a median age of 47 and 52% were male. Indications for transplant included acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia, B-cell lymphoma, myelodysplastic syndrome/myelofibrosis, and other unspecified indications.

In both the Orca-T and control cohorts, patients underwent myeloablative conditioning from 10 to 2 days prior to stem cell infusion.

As noted patients in the experimental arm received infusion of hematopoietic stem/progenitor cells and Tregs, followed 2 days later by conventional T-cell infusion, and, on the day after that, tacrolimus at a target dose of 4.6 ng/mL. The conventional T cells were reserved from donor apheresis and were otherwise unmanipulated prior to infusion into the recipient, Dr. Meyer noted.

Patients in the standard-of-care arm received tacrolimus on the day before standard infusion of the apheresis product, followed by methotrexate prophylaxis on days 1, 3, 6 and 11.

Time to neutrophil engraftment, platelet engraftment, and from day 0 to hospital discharge were all significantly shorter in the Orca-T group, at 12 versus 14 days (P < .0001), 11 vs. 17 days (P < .0001), and 15 vs. 17 days (P = .01) respectively.

At 100 days of follow-up, the rate of grade 2 or greater acute GVHD was 30% among standard-of-care patients versus 10% among Orca-T–treated patients. At 1-year follow-up, respective rates of chronic GVHD were 46% vs. 3%.
 

Safety

“In general, the protocol is extremely well tolerated by our patients. We’ve seen no exceptional infectious disease complications, and we’ve seen no other major complications,” Dr. Meyer said.

Cytomegalovirus prophylaxis was used variably, depending on the center and on the attending physician. Epstein-Barr virus reactivation occurred in eight patients, with one requiring therapy, but there was no biopsy or radiographic evidence of posttransplant lymphoproliferative disorder.

In all, 18% of patients had serious adverse events during the reporting period, all of which resolved. There were no treatment-related deaths in the Orca-T arm, compared with 11% of controls.
 

Engraftment differences explored

In the question-and-answer session following the presentation, Christopher J. Gamper, MD, PhD, from the Johns Hopkins Hospital in Baltimore, told Dr. Meyer that “your outcomes from Orca-T look excellent,” and asked about the cost differential, compared with similar, unmanipulated transplants performed with standard GVHD prophylaxis.

“Is this recovered by lower costs for treatment of GVHD?” he asked.

“I have not done an economic cost analysis of course, and I think others may be looking into this,” Dr. Meyer replied. “Graft engineering can be expensive, although it’s an engineering proposition and one could imagine that the costs will go down substantially over time.”

Session moderator Alan Hanash, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York, commented on the differences in engraftment between the experimental controls arms, and asked Dr. Meyer: “Do you think this is due to the difference in prophylaxis? Absence of methotrexate? Do you think that it could be a direct impact of regulatory T cells on hematopoietic engraftment?”

“Certainly not having methotrexate is beneficial for engraftment, and may account for the differences we see, Dr. Meyer said. “However, it is possible that Tregs could be playing a facilitative role. There certainly is good preclinical literature that Tregs, particularly in the bone marrow space, can facilitate bone marrow engraftment.”

The Orca-T trials are sponsored by Orca Bio and Stanford, with support from the National Institutes of Health. Dr. Meyer receives research support from Orca and is a scientific adviser to GigaGen, Triursus, Incyte, and Indee Labs. Dr. Hanash and Dr. Gamper had no relevant disclosures.

A novel T-cell engineered product, Orca-T (Orca Bio), was associated with lower incidence of both acute and chronic graft-versus-host disease (GVHD) and more than double the rate of GVHD-free and relapse-free survival, compared with the current standard of care for patients undergoing hematopoietic stem cell transplants (HSCT), investigators said.

In both a multicenter phase 1 trial (NCT04013685) and single-center phase 1/2 trial (NCT01660607) with a total of 50 patients, those who received Orca-T with single-agent GVHD prophylaxis had a 1-year GVHD-free and relapse-free survival rate of 75%, compared with 31% for patients who received standard of care with two-agent prophylaxis, reported Everett H. Meyer, MD, PhD, from the Stanford (Calif.) University.

“Orca-T has good evidence for reduced acute graft-versus-host disease, reduced chromic graft-versus-host disease, and a low nonrelapse mortality,” he said at the Transplant & Cellular Therapies Meetings.

The product can be quickly manufactured and delivered to treatment centers across the continental United States, with “vein-to-vein” time of less than 72 hours, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Orca-T consists of highly purified, donor-derived T-regulatory (Treg) cells that are sorted and delivered on day 0 with hematopoietic stem cells, without immunosuppressants, followed 2 days later with infusion of a matching dose of conventional T cells.

“The Treg cells are allowed to expand to create the right microenvironment for the [conventional T cells],” he explained.

In preclinical studies, donor-derived, high-purity Tregs delivered prior to adoptive transfer of conventional T cells prevented GVHD while maintaining graft-versus-tumor immunity, he said.
 

Two T-cell infusions

He reported updated results from current studies on a total of 50 adults, with a cohort of 144 patients treated concurrently with standard of care as controls.

The Orca-T–treated patients had a median age of 47 and 52% were male. Indications for transplant included acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia, B-cell lymphoma, myelodysplastic syndrome/myelofibrosis, and other unspecified indications.

In both the Orca-T and control cohorts, patients underwent myeloablative conditioning from 10 to 2 days prior to stem cell infusion.

As noted patients in the experimental arm received infusion of hematopoietic stem/progenitor cells and Tregs, followed 2 days later by conventional T-cell infusion, and, on the day after that, tacrolimus at a target dose of 4.6 ng/mL. The conventional T cells were reserved from donor apheresis and were otherwise unmanipulated prior to infusion into the recipient, Dr. Meyer noted.

Patients in the standard-of-care arm received tacrolimus on the day before standard infusion of the apheresis product, followed by methotrexate prophylaxis on days 1, 3, 6 and 11.

Time to neutrophil engraftment, platelet engraftment, and from day 0 to hospital discharge were all significantly shorter in the Orca-T group, at 12 versus 14 days (P < .0001), 11 vs. 17 days (P < .0001), and 15 vs. 17 days (P = .01) respectively.

At 100 days of follow-up, the rate of grade 2 or greater acute GVHD was 30% among standard-of-care patients versus 10% among Orca-T–treated patients. At 1-year follow-up, respective rates of chronic GVHD were 46% vs. 3%.
 

Safety

“In general, the protocol is extremely well tolerated by our patients. We’ve seen no exceptional infectious disease complications, and we’ve seen no other major complications,” Dr. Meyer said.

Cytomegalovirus prophylaxis was used variably, depending on the center and on the attending physician. Epstein-Barr virus reactivation occurred in eight patients, with one requiring therapy, but there was no biopsy or radiographic evidence of posttransplant lymphoproliferative disorder.

In all, 18% of patients had serious adverse events during the reporting period, all of which resolved. There were no treatment-related deaths in the Orca-T arm, compared with 11% of controls.
 

Engraftment differences explored

In the question-and-answer session following the presentation, Christopher J. Gamper, MD, PhD, from the Johns Hopkins Hospital in Baltimore, told Dr. Meyer that “your outcomes from Orca-T look excellent,” and asked about the cost differential, compared with similar, unmanipulated transplants performed with standard GVHD prophylaxis.

“Is this recovered by lower costs for treatment of GVHD?” he asked.

“I have not done an economic cost analysis of course, and I think others may be looking into this,” Dr. Meyer replied. “Graft engineering can be expensive, although it’s an engineering proposition and one could imagine that the costs will go down substantially over time.”

Session moderator Alan Hanash, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York, commented on the differences in engraftment between the experimental controls arms, and asked Dr. Meyer: “Do you think this is due to the difference in prophylaxis? Absence of methotrexate? Do you think that it could be a direct impact of regulatory T cells on hematopoietic engraftment?”

“Certainly not having methotrexate is beneficial for engraftment, and may account for the differences we see, Dr. Meyer said. “However, it is possible that Tregs could be playing a facilitative role. There certainly is good preclinical literature that Tregs, particularly in the bone marrow space, can facilitate bone marrow engraftment.”

The Orca-T trials are sponsored by Orca Bio and Stanford, with support from the National Institutes of Health. Dr. Meyer receives research support from Orca and is a scientific adviser to GigaGen, Triursus, Incyte, and Indee Labs. Dr. Hanash and Dr. Gamper had no relevant disclosures.

A novel quantitative assay used with flow cytometry helps to precisely measure chimeric antigen receptor (CAR) T-cell engraftment and in vivo expansion to predict patient outcomes after CAR T-cell infusion, according to researchers at the Fondazione IRCCS Istituto Nazionale Tumorion in Milan.

Higher frequencies of CAR-positive T cells at day 9 after infusion, as measured using the polymerase chain reaction (PCR)-based assay, accurately distinguished responders from nonresponders, Paolo Corradini, MD, said at the 3rd European CAR T-cell Meeting.

The findings, first presented in December at the American Society of Hematology annual conference, suggest the assay could improve treatment decision-making, Dr. Corradini of the University of Milan said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association

He and his colleagues prospectively collected samples from 16 patients with diffuse large B-cell lymphoma, 5 with transformed follicular lymphoma, and 7 with primary mediastinal B-cell lymphoma who were treated with either axicabtagene ciloleucel (axi-cel; Yescarta) or tisagenlecleucel (tisa-cal; Kymriah) between November 2019 and July 2020. CAR T cells were monitored using flow cytometry.

Pivotal trial data and subsequent findings with respect to tisa-cel and axi-cel have demonstrated that CAR T-cell engraftment and in vivo expansion have a crucial impact on disease response and toxicity: a cut-off value of CAR+ cells at day 9 greater than 24.5/microliters distinguished responders from nonresponders with a sensitivity of 87.5% and specificity of 81%, Dr. Corradini noted.

“But we have also devised a methodology by digital droplet PCR (ddPCR) recently that correlates perfectly with the flow cytometry data,” he said, adding that the assay is “easy and allowed precise enumeration of the CAR T cells in the blood of the patient.”

The R square (coefficient of determination) for ddPCR and flow cytometry was 0.9995 and 0.9997 for tisa-cel and axi-cel, respectively (P < .0001 for each). This is particularly useful for assessing whether low CAR T-cell levels on flow cytometry are background signals resulting from nonspecific binding of the antibodies or true low levels, and the findings therefore have implications for improving clinical decision-making and outcomes in CAR T-cell therapy recipients, he said.

[email protected]

A novel quantitative assay used with flow cytometry helps to precisely measure chimeric antigen receptor (CAR) T-cell engraftment and in vivo expansion to predict patient outcomes after CAR T-cell infusion, according to researchers at the Fondazione IRCCS Istituto Nazionale Tumorion in Milan.

Higher frequencies of CAR-positive T cells at day 9 after infusion, as measured using the polymerase chain reaction (PCR)-based assay, accurately distinguished responders from nonresponders, Paolo Corradini, MD, said at the 3rd European CAR T-cell Meeting.

The findings, first presented in December at the American Society of Hematology annual conference, suggest the assay could improve treatment decision-making, Dr. Corradini of the University of Milan said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association

He and his colleagues prospectively collected samples from 16 patients with diffuse large B-cell lymphoma, 5 with transformed follicular lymphoma, and 7 with primary mediastinal B-cell lymphoma who were treated with either axicabtagene ciloleucel (axi-cel; Yescarta) or tisagenlecleucel (tisa-cal; Kymriah) between November 2019 and July 2020. CAR T cells were monitored using flow cytometry.

Pivotal trial data and subsequent findings with respect to tisa-cel and axi-cel have demonstrated that CAR T-cell engraftment and in vivo expansion have a crucial impact on disease response and toxicity: a cut-off value of CAR+ cells at day 9 greater than 24.5/microliters distinguished responders from nonresponders with a sensitivity of 87.5% and specificity of 81%, Dr. Corradini noted.

“But we have also devised a methodology by digital droplet PCR (ddPCR) recently that correlates perfectly with the flow cytometry data,” he said, adding that the assay is “easy and allowed precise enumeration of the CAR T cells in the blood of the patient.”

The R square (coefficient of determination) for ddPCR and flow cytometry was 0.9995 and 0.9997 for tisa-cel and axi-cel, respectively (P < .0001 for each). This is particularly useful for assessing whether low CAR T-cell levels on flow cytometry are background signals resulting from nonspecific binding of the antibodies or true low levels, and the findings therefore have implications for improving clinical decision-making and outcomes in CAR T-cell therapy recipients, he said.

[email protected]

A novel quantitative assay used with flow cytometry helps to precisely measure chimeric antigen receptor (CAR) T-cell engraftment and in vivo expansion to predict patient outcomes after CAR T-cell infusion, according to researchers at the Fondazione IRCCS Istituto Nazionale Tumorion in Milan.

Higher frequencies of CAR-positive T cells at day 9 after infusion, as measured using the polymerase chain reaction (PCR)-based assay, accurately distinguished responders from nonresponders, Paolo Corradini, MD, said at the 3rd European CAR T-cell Meeting.

The findings, first presented in December at the American Society of Hematology annual conference, suggest the assay could improve treatment decision-making, Dr. Corradini of the University of Milan said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association

He and his colleagues prospectively collected samples from 16 patients with diffuse large B-cell lymphoma, 5 with transformed follicular lymphoma, and 7 with primary mediastinal B-cell lymphoma who were treated with either axicabtagene ciloleucel (axi-cel; Yescarta) or tisagenlecleucel (tisa-cal; Kymriah) between November 2019 and July 2020. CAR T cells were monitored using flow cytometry.

Pivotal trial data and subsequent findings with respect to tisa-cel and axi-cel have demonstrated that CAR T-cell engraftment and in vivo expansion have a crucial impact on disease response and toxicity: a cut-off value of CAR+ cells at day 9 greater than 24.5/microliters distinguished responders from nonresponders with a sensitivity of 87.5% and specificity of 81%, Dr. Corradini noted.

“But we have also devised a methodology by digital droplet PCR (ddPCR) recently that correlates perfectly with the flow cytometry data,” he said, adding that the assay is “easy and allowed precise enumeration of the CAR T cells in the blood of the patient.”

The R square (coefficient of determination) for ddPCR and flow cytometry was 0.9995 and 0.9997 for tisa-cel and axi-cel, respectively (P < .0001 for each). This is particularly useful for assessing whether low CAR T-cell levels on flow cytometry are background signals resulting from nonspecific binding of the antibodies or true low levels, and the findings therefore have implications for improving clinical decision-making and outcomes in CAR T-cell therapy recipients, he said.

[email protected]

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.

Steroids are usually the first choice of therapy for the treatment of patients with graft-vs.-host disease (GVHD), but complications from steroid use may carry a high financial cost, investigators caution.

Among 689 patients with a diagnosis of GVHD following a hematopoietic stem cell transplant (HSCT) who received steroids, 685 (97%) had at least one steroid-related complication, resulting in nearly $165,000 in mean health-care costs over 24 months, said Elizabeth J. Bell, PhD, MPH, an epidemiologist at Optum Inc.

“For both acute and chronic GVHD, the standard of care for first-line treatment is systemic steroids. The complications associated with steroid treatment are well known. However, the health-care resources utilized and the costs incurred by these patients are not well-quantified,” she said at the Transplantation & Cellular Therapies Meetings (Abstract 12).

Dr. Bell reported the results of a retrospective database analysis on costs associated with steroid complications in HSCT recipients at the meeting, which was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

She and colleagues from Optum, Incyte, and the University of Minnesota in Minneapolis looked at data on 689 patients with a diagnosis of GVHD after HSCT who received systemic steroids from July 1, 2010, through Aug. 31, 2019. The data were extracted from the Optum Research database, and included U.S. commercial and Medicare Advantage patients.

They looked at total complications and steroid-associated complications in each of four categories: infections; metabolic or endocrine complications (for example, diabetes, dyslipidemia); gastrointestinal (GI) complications (e.g., peptic ulcer disease); and bone or muscle complications (myopathy, etc).

They estimated costs based on International Classification of Diseases (ICD) codes for any steroid complications during the 24 months after steroid initiation, including those complications that may have been present at the time of GVHD diagnosis.

The median patient age was 55 years, and 60% of the sample were male. The mean Charlson Comorbidity Index score at baseline was 3.

Overall, 22% of patients had only acute GVHD, 21% had only chronic GVHD, and 39% had both acute and chronic disease. The GVHD type was unspecified in the remaining 18%.

The median time from GVHD diagnosis to initiating steroids was 30 days for patients with both acute and chronic disease, as well as those with both presentations. The median time to initiation was 36 days for patients with unspecified GVHD type.

The median cumulative duration of steroid use over 24 months was 62 days for patients with acute GVHD, 208 days for those with chronic GVHD, 166 days for those with both, and 74 days for patients with unspecified GVHD type.

As noted before, complications occurred in 97% of patients, with infections being the most common complications, occurring in 80% of patients, followed by metabolic/endocrine complications in 32%, gastrointestinal in 29%, and bone/muscle complications in 20%.

For the 665 patients who had any steroid-related complication, the mean costs of steroid-associated care in the 24 months after they were started on steroids was $164,787, and the median cost was $50,834.

Health care costs were highest among patients with infections, at a mean of $167,473, and a median of $57,680, followed by bone/muscle conditions ($75,289 and $2,057, respectively), GI conditions ($67,861 and $3,360), and metabolic or endocrine conditions ($47, 101 and $1,164).

In all categories, hospitalizations accounted for the large majority of costs.

Two-thirds (66%) of patients who experienced any steroid-related complication required hospitalization, primarily for infections.

Among all patients with complications, the median cumulative hospital stay over 24 months was 20 days, with bone/muscle complications and infections associated with a median of 19 and 18 days of hospitalization, respectively.

Dr. Bell acknowledged that the study was limited by use of ICD coding to identify steroid complication-related health-care utilization and costs, which can be imprecise, and by the fact that the analysis included only complications resulting in health care use as documented in medical claims. In addition, the investigators noted that they could not control for the possibility that steroids exacerbated conditions that existed at baseline.

“These findings emphasize the need to cautiously evaluate the treatment options for patients with GVHD. Future study with medical records is needed to provide insights on the clinical aspects of the complications (e.g., severity and suspected causality),” Dr. Bell and colleagues concluded in the study’s abstract.
 

Definitions questioned

An HSCT specialist approached for comment said that the findings of the study made sense, but she had questions regarding the study methodology.

“I would intuitively think that steroid-associated complications are a major cause of health care use in GVHD patients and it’s interesting to see that there is emerging data to support this hypothesis,” HSCT specialist Hélène Schoemans, MD of the University of Leuven, Belgium, said in an interview.

She noted, however, that “it is surprising that the period of steroid initiation was the same for acute and chronic GVHD,” and questioned whether that anomalous finding could be due to the study’s definition of acute and chronic GVHD or to how the period from baseline to steroid initiation was defined.

The questions about the definitions and timing of therapy make it uncertain as to whether the complications reported were caused by steroids or by some other factor, she suggested.

The study was supported by Optum Inc. Dr. Bell is an employee of the company, and a paid consultant of Incyte. Dr. Schoemans has received travel expenses from Celgene, Abbvie, and Incyte; is part of the advisory boards for Incyte; and has received speakers fees from Novartis, Incyte, Jazz Pharmaceuticals, and Takeda.