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Cortactin expression aids in CLL-MCL differential
The presence or absence in tumor cells of cortactin, a cytoskeleton-remodeling adapter protein, may be a marker to help pathologists distinguish between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), investigators suggest.
A study of cortactin expression in tumor samples from patients with B-cell CLL, MCL, and other hematologic malignancies showed that while cortactin was present in 14 of 17 CLL samples, it was not expressed on any of 16 MCL samples, reported Marco Pizzi, MD, PhD, from the University of Padova (Italy) and his colleagues.
“In particular, cortactin may contribute to the differential diagnosis between CLL and MCL, two neoplasms with similar histological features but very different clinical outcome. Further studies are needed to clarify the molecular mechanisms of deranged cortactin expression in MCL and CLL and to investigate any possible relationship between cortactin status and the biological features of these lymphomas,” they wrote in Human Pathology.
Overexpression of cortactin has been reported in several solid tumors, and increased expression of CTTN, the gene encoding for cortactin, has been associated with aggressive, poor prognosis disease, the investigators noted.
To characterize cortactin expression in lymphoid and hematopoietic cells and detect potential associations between cortactin and virulence of hematologic malignancies, the investigators performed immunohistochemical analysis on samples from 131 patients treated at their center. The samples included 17 cases of CLL, 16 of MCL, 25 of follicular lymphoma (FL), 30 of marginal zone lymphoma (MZL), 10 of hairy cell leukemia, three of splenic diffuse red pulp small B-cell lymphomas (SDRPBL), and 30 of diffuse large B-cell lymphoma (DLBCL).
They found that cortactin was expressed in 14 of the 17 CLL samples, all 10 of the HCL samples, and 22 of the 30 DLBCL samples. In contrast, there was no cortactin expression detected in any of either 16 MCL or three SDRPBL samples. The researchers found that 13 of 30 MZL samples had low-level staining. In FL, cortactin was expressed in 2 of the samples but in the remaining 23 cases the researchers found only scattered cortactin-positive lymphoid elements of non–B-cell lineage.
The investigators also found that cortactin expression in CLL correlated with other CLL-specific markers, and found that expression of two or more of the markers had 89.1% sensitivity, 100% specificity, a 100% positive predictive value, and 90.5% negative predictive value for a diagnosis of CLL.
In addition, they saw that the immunohistochemical results were similar to those for CTTN gene expression assessed by in silico analysis.
The investigators noted that CLL and MCL are challenging to differentiate from one another because of morphologic similarities and partially overlapping immunophenotypes.
“In this context, cortactin expression would strongly sustain a diagnosis of CLL over MCL, particularly in association with other CLL markers (i.e., LEF1 and CD200),” they wrote.
The study was internally supported. The authors declared no conflicts of interest.
SOURCE: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
The presence or absence in tumor cells of cortactin, a cytoskeleton-remodeling adapter protein, may be a marker to help pathologists distinguish between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), investigators suggest.
A study of cortactin expression in tumor samples from patients with B-cell CLL, MCL, and other hematologic malignancies showed that while cortactin was present in 14 of 17 CLL samples, it was not expressed on any of 16 MCL samples, reported Marco Pizzi, MD, PhD, from the University of Padova (Italy) and his colleagues.
“In particular, cortactin may contribute to the differential diagnosis between CLL and MCL, two neoplasms with similar histological features but very different clinical outcome. Further studies are needed to clarify the molecular mechanisms of deranged cortactin expression in MCL and CLL and to investigate any possible relationship between cortactin status and the biological features of these lymphomas,” they wrote in Human Pathology.
Overexpression of cortactin has been reported in several solid tumors, and increased expression of CTTN, the gene encoding for cortactin, has been associated with aggressive, poor prognosis disease, the investigators noted.
To characterize cortactin expression in lymphoid and hematopoietic cells and detect potential associations between cortactin and virulence of hematologic malignancies, the investigators performed immunohistochemical analysis on samples from 131 patients treated at their center. The samples included 17 cases of CLL, 16 of MCL, 25 of follicular lymphoma (FL), 30 of marginal zone lymphoma (MZL), 10 of hairy cell leukemia, three of splenic diffuse red pulp small B-cell lymphomas (SDRPBL), and 30 of diffuse large B-cell lymphoma (DLBCL).
They found that cortactin was expressed in 14 of the 17 CLL samples, all 10 of the HCL samples, and 22 of the 30 DLBCL samples. In contrast, there was no cortactin expression detected in any of either 16 MCL or three SDRPBL samples. The researchers found that 13 of 30 MZL samples had low-level staining. In FL, cortactin was expressed in 2 of the samples but in the remaining 23 cases the researchers found only scattered cortactin-positive lymphoid elements of non–B-cell lineage.
The investigators also found that cortactin expression in CLL correlated with other CLL-specific markers, and found that expression of two or more of the markers had 89.1% sensitivity, 100% specificity, a 100% positive predictive value, and 90.5% negative predictive value for a diagnosis of CLL.
In addition, they saw that the immunohistochemical results were similar to those for CTTN gene expression assessed by in silico analysis.
The investigators noted that CLL and MCL are challenging to differentiate from one another because of morphologic similarities and partially overlapping immunophenotypes.
“In this context, cortactin expression would strongly sustain a diagnosis of CLL over MCL, particularly in association with other CLL markers (i.e., LEF1 and CD200),” they wrote.
The study was internally supported. The authors declared no conflicts of interest.
SOURCE: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
The presence or absence in tumor cells of cortactin, a cytoskeleton-remodeling adapter protein, may be a marker to help pathologists distinguish between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), investigators suggest.
A study of cortactin expression in tumor samples from patients with B-cell CLL, MCL, and other hematologic malignancies showed that while cortactin was present in 14 of 17 CLL samples, it was not expressed on any of 16 MCL samples, reported Marco Pizzi, MD, PhD, from the University of Padova (Italy) and his colleagues.
“In particular, cortactin may contribute to the differential diagnosis between CLL and MCL, two neoplasms with similar histological features but very different clinical outcome. Further studies are needed to clarify the molecular mechanisms of deranged cortactin expression in MCL and CLL and to investigate any possible relationship between cortactin status and the biological features of these lymphomas,” they wrote in Human Pathology.
Overexpression of cortactin has been reported in several solid tumors, and increased expression of CTTN, the gene encoding for cortactin, has been associated with aggressive, poor prognosis disease, the investigators noted.
To characterize cortactin expression in lymphoid and hematopoietic cells and detect potential associations between cortactin and virulence of hematologic malignancies, the investigators performed immunohistochemical analysis on samples from 131 patients treated at their center. The samples included 17 cases of CLL, 16 of MCL, 25 of follicular lymphoma (FL), 30 of marginal zone lymphoma (MZL), 10 of hairy cell leukemia, three of splenic diffuse red pulp small B-cell lymphomas (SDRPBL), and 30 of diffuse large B-cell lymphoma (DLBCL).
They found that cortactin was expressed in 14 of the 17 CLL samples, all 10 of the HCL samples, and 22 of the 30 DLBCL samples. In contrast, there was no cortactin expression detected in any of either 16 MCL or three SDRPBL samples. The researchers found that 13 of 30 MZL samples had low-level staining. In FL, cortactin was expressed in 2 of the samples but in the remaining 23 cases the researchers found only scattered cortactin-positive lymphoid elements of non–B-cell lineage.
The investigators also found that cortactin expression in CLL correlated with other CLL-specific markers, and found that expression of two or more of the markers had 89.1% sensitivity, 100% specificity, a 100% positive predictive value, and 90.5% negative predictive value for a diagnosis of CLL.
In addition, they saw that the immunohistochemical results were similar to those for CTTN gene expression assessed by in silico analysis.
The investigators noted that CLL and MCL are challenging to differentiate from one another because of morphologic similarities and partially overlapping immunophenotypes.
“In this context, cortactin expression would strongly sustain a diagnosis of CLL over MCL, particularly in association with other CLL markers (i.e., LEF1 and CD200),” they wrote.
The study was internally supported. The authors declared no conflicts of interest.
SOURCE: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
FROM HUMAN PATHOLOGY
Key clinical point:
Major finding: Cortactin was expressed on 14 of 17 CLL samples vs. none of 16 MCL samples.
Study details: Immunohistochemistry analysis of samples from 131 patients with B-cell lineage non-Hodgkin lymphomas.
Disclosures: The study was internally supported. The authors reported having no conflicts of interest.
Source: Pizzi M et al. Hum Pathol. 2018 Nov 17. doi: 10.1016/j.humpath.2018.10.038.
ASH expands late-breaking abstract session
An additional presentation has been added to the late-breaking abstract session of the 2018 ASH Annual Meeting.
The session was expanded from six abstracts to seven this year because of a record number of “exciting” submissions, according to ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland.
“We received 98 late-breaking abstracts, which is a record,” Dr. Brodsky said.
“They were so exciting this year that we added a seventh, and, quite frankly, we could have added several more, but we just didn’t have time in the meeting.”
Dr. Brodsky discussed this year’s late-breaking abstracts during a recent press briefing.
Abstract LBA-1 reports results of rivaroxaban thromboprophylaxis in cancer patients with an increased risk of venous thromboembolism (VTE). Compared to placebo, rivaroxaban significantly reduced VTE and VTE-related death during treatment but not over the entire study period.
Abstract LBA-2 describes a phase 3, randomized trial comparing daratumumab plus lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The addition of daratumumab reduced the risk of disease progression or death by 45%.
Abstract LBA-3 details results with HemoTypeSC, a test used to detect sickle cell trait and sickle cell disease. The test correctly identified all phenotypes in the 1,000 children studied.
Abstract LBA-4 describes a randomized, phase 3 study comparing ibrutinib plus rituximab to fludarabine, cyclophosphamide, and rituximab in younger patients with untreated chronic lymphocytic leukemia (CLL). Investigators found that ibrutinib plus rituximab provided significantly better progression-free and overall survival than the three-drug combination.
Abstract LBA-5 details a strategy for direct oral anticoagulant use in patients with atrial fibrillation undergoing surgery. Investigators say the strategy is likely to be “practice-changing” and incorporated into guidelines.
Abstract LBA-6 covers a trial of emapalumab in patients with primary hemophagocytic lymphohistiocytosis. Emapalumab, which was recently approved by the U.S. Food and Drug Administration, produced responses in most of the 34 patients studied and had a favorable safety profile, according to investigators.
Abstract LBA-7 reports the discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax in patients with progressive CLL. Investigators say this mutation could be a biomarker of CLL relapse.
An additional presentation has been added to the late-breaking abstract session of the 2018 ASH Annual Meeting.
The session was expanded from six abstracts to seven this year because of a record number of “exciting” submissions, according to ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland.
“We received 98 late-breaking abstracts, which is a record,” Dr. Brodsky said.
“They were so exciting this year that we added a seventh, and, quite frankly, we could have added several more, but we just didn’t have time in the meeting.”
Dr. Brodsky discussed this year’s late-breaking abstracts during a recent press briefing.
Abstract LBA-1 reports results of rivaroxaban thromboprophylaxis in cancer patients with an increased risk of venous thromboembolism (VTE). Compared to placebo, rivaroxaban significantly reduced VTE and VTE-related death during treatment but not over the entire study period.
Abstract LBA-2 describes a phase 3, randomized trial comparing daratumumab plus lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The addition of daratumumab reduced the risk of disease progression or death by 45%.
Abstract LBA-3 details results with HemoTypeSC, a test used to detect sickle cell trait and sickle cell disease. The test correctly identified all phenotypes in the 1,000 children studied.
Abstract LBA-4 describes a randomized, phase 3 study comparing ibrutinib plus rituximab to fludarabine, cyclophosphamide, and rituximab in younger patients with untreated chronic lymphocytic leukemia (CLL). Investigators found that ibrutinib plus rituximab provided significantly better progression-free and overall survival than the three-drug combination.
Abstract LBA-5 details a strategy for direct oral anticoagulant use in patients with atrial fibrillation undergoing surgery. Investigators say the strategy is likely to be “practice-changing” and incorporated into guidelines.
Abstract LBA-6 covers a trial of emapalumab in patients with primary hemophagocytic lymphohistiocytosis. Emapalumab, which was recently approved by the U.S. Food and Drug Administration, produced responses in most of the 34 patients studied and had a favorable safety profile, according to investigators.
Abstract LBA-7 reports the discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax in patients with progressive CLL. Investigators say this mutation could be a biomarker of CLL relapse.
An additional presentation has been added to the late-breaking abstract session of the 2018 ASH Annual Meeting.
The session was expanded from six abstracts to seven this year because of a record number of “exciting” submissions, according to ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland.
“We received 98 late-breaking abstracts, which is a record,” Dr. Brodsky said.
“They were so exciting this year that we added a seventh, and, quite frankly, we could have added several more, but we just didn’t have time in the meeting.”
Dr. Brodsky discussed this year’s late-breaking abstracts during a recent press briefing.
Abstract LBA-1 reports results of rivaroxaban thromboprophylaxis in cancer patients with an increased risk of venous thromboembolism (VTE). Compared to placebo, rivaroxaban significantly reduced VTE and VTE-related death during treatment but not over the entire study period.
Abstract LBA-2 describes a phase 3, randomized trial comparing daratumumab plus lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The addition of daratumumab reduced the risk of disease progression or death by 45%.
Abstract LBA-3 details results with HemoTypeSC, a test used to detect sickle cell trait and sickle cell disease. The test correctly identified all phenotypes in the 1,000 children studied.
Abstract LBA-4 describes a randomized, phase 3 study comparing ibrutinib plus rituximab to fludarabine, cyclophosphamide, and rituximab in younger patients with untreated chronic lymphocytic leukemia (CLL). Investigators found that ibrutinib plus rituximab provided significantly better progression-free and overall survival than the three-drug combination.
Abstract LBA-5 details a strategy for direct oral anticoagulant use in patients with atrial fibrillation undergoing surgery. Investigators say the strategy is likely to be “practice-changing” and incorporated into guidelines.
Abstract LBA-6 covers a trial of emapalumab in patients with primary hemophagocytic lymphohistiocytosis. Emapalumab, which was recently approved by the U.S. Food and Drug Administration, produced responses in most of the 34 patients studied and had a favorable safety profile, according to investigators.
Abstract LBA-7 reports the discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax in patients with progressive CLL. Investigators say this mutation could be a biomarker of CLL relapse.
CAR T-cell studies to be presented at ASH
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.
Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.
One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).
Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).
A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.
ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.
Ibrutinib
In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.
Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.
Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.
Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.
These findings are “early and preliminary but very exciting” Dr. Brodsky said.
Checkpoint inhibitors
Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.
The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.
CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.
Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.
Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.
There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.
“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.
“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”
Tisagenlecleucel follow-up
One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.
The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.
The probability of relapse-free survival was 66% at 12 months and 18 months.
“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.
The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).
The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.
HSCT consolidation
Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).
Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.
Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.
There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.
Of the 23 patients who did not undergo another HSCT, eight are still in remission.
“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.
ASH 2018 coming attractions look at the big picture
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
Biosimilar deemed equivalent to rituximab in FL
Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).
Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.
In addition, adverse event (AE) profiles were comparable between the treatment arms.
Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.
CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.
The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).
Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
Efficacy
The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.
The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.
The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.
Safety
Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.
The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:
- Infusion-related reactions (31% and 29%)
- Infections (27% and 21%)
- Worsening neutropenia (22% for both)
- Upper respiratory tract infection (12% and 11%)
- Worsening anemia (10% and 14%)
- Worsening thrombocytopenia (8% and 7%)
- Fatigue (7% and 9%)
- Diarrhea (5% for both)
- Nausea (5% for both)
- Urinary tract infection (4% and 5%)
- Headache (3% and 5%).
Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.
Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.
There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.
This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.
Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).
Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.
In addition, adverse event (AE) profiles were comparable between the treatment arms.
Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.
CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.
The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).
Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
Efficacy
The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.
The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.
The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.
Safety
Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.
The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:
- Infusion-related reactions (31% and 29%)
- Infections (27% and 21%)
- Worsening neutropenia (22% for both)
- Upper respiratory tract infection (12% and 11%)
- Worsening anemia (10% and 14%)
- Worsening thrombocytopenia (8% and 7%)
- Fatigue (7% and 9%)
- Diarrhea (5% for both)
- Nausea (5% for both)
- Urinary tract infection (4% and 5%)
- Headache (3% and 5%).
Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.
Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.
There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.
This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.
Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
Phase 3 results suggest the biosimilar product CT-P10 is equivalent to rituximab in patients with low-tumor-burden follicular lymphoma (FL).
Overall response rates were similar—both exceeding 80%—in patients who received CT-P10 and those who received rituximab.
In addition, adverse event (AE) profiles were comparable between the treatment arms.
Larry W. Kwak, MD, PhD, of City of Hope in Duarte, California, and his colleagues reported these results in The Lancet Haematology.
CT-P10 was approved by the European Commission in 2017 and was recommended for approval by the U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee last month.
The phase 3 trial of CT-P10 included 258 patients with stage II-IV low-tumor-burden FL. They were randomized to receive CT-P10 (n=130) or rituximab (n=128).
Patients received intravenous CT-P10 or rituximab weekly for 4 weeks as induction therapy. Patients experiencing disease control went on to a maintenance phase with their assigned treatment, given every 8 weeks for six cycles, followed by another year of maintenance therapy with CT-P10 for those still on study.
Efficacy
The overall response rate at 7 months was 83% in patients randomized to CT-P10 and 81% in those randomized to rituximab.
The complete response rates were 28% and 34%, respectively. The unconfirmed complete response rates were 5% and 2%, respectively. And the partial response rates were 51% and 46%, respectively.
The two treatments were deemed therapeutically equivalent, as the two-sided 90% confidence intervals for the difference in proportion of responders between CT-P10 and rituximab were within the prespecified equivalence margin of 17%.
Safety
Treatment-emergent AEs occurred in 71% of patients in the CT-P10 arm and 67% of those in the rituximab arm.
The most common treatment-emergent AEs (in the CT-P10 and rituximab arms, respectively) were:
- Infusion-related reactions (31% and 29%)
- Infections (27% and 21%)
- Worsening neutropenia (22% for both)
- Upper respiratory tract infection (12% and 11%)
- Worsening anemia (10% and 14%)
- Worsening thrombocytopenia (8% and 7%)
- Fatigue (7% and 9%)
- Diarrhea (5% for both)
- Nausea (5% for both)
- Urinary tract infection (4% and 5%)
- Headache (3% and 5%).
Serious AEs were reported in six patients in the CT-P10 arm and three patients in the rituximab arm.
Two serious AEs—myocardial infarction and constipation—in the CT-P10 arm were considered related to treatment. None of the serious AEs in the rituximab arm were considered treatment-related.
Two patients in the CT-P10 arm discontinued treatment due to AEs—one due to myocardial infarction and one due to dermatitis. There were no AE-related discontinuations in the rituximab arm.
There were two deaths in the CT-P10 arm as of the cutoff date (January 4, 2018). One was due to myocardial infarction, and one was due to respiratory failure. The myocardial infarction was considered possibly related to treatment.
This trial was sponsored by Celltrion, the company developing CT-P10. Three study authors are employees of the company.
Dr. Kwak and several other authors not employed by Celltrion reported disclosures related to the company. Authors also reported relationships with Novartis, Roche, AbbVie, Celgene, and Takeda, among other entities.
Elderly NHL patients have higher NRM after HSCT
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).
The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.
However, the 3-year rate of relapse was similar across the age groups.
Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.
The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.
The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).
At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.
Results
The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).
NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).
Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).
In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).
The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.
After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”
Therefore, age remains an independent risk factor.
The investigators did not report conflicts of interest.
Bortezomib may overcome resistance in WM
Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.
Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.
The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.
Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.
The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.
All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.
The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.
Bortezomib was given at 1.6 mg/m2 on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m2 on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The median follow-up was 90.7 months.
The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).
The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.
“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.
“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”
The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.
Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.
This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.
Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.
The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.
Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.
The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.
All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.
The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.
Bortezomib was given at 1.6 mg/m2 on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m2 on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The median follow-up was 90.7 months.
The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).
The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.
“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.
“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”
The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.
Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.
This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.
Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.
The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.
Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.
The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.
All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.
The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.
Bortezomib was given at 1.6 mg/m2 on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m2 on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The median follow-up was 90.7 months.
The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).
The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.
“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.
“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”
The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.
Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.
This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
FDA expands approval of brentuximab vedotin to PTCL
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
R-CHOP effective as first-line treatment in FL
Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).
In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.
Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.
The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.
Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.
The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.
Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.
The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.
Overall results
The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).
The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).
At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).
The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).
There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.
The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.
Focus on grade 1-3a FL
Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.
Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.
Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.
The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.
This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.
Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.
Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).
In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.
Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.
The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.
Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.
The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.
Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.
The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.
Overall results
The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).
The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).
At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).
The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).
There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.
The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.
Focus on grade 1-3a FL
Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.
Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.
Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.
The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.
This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.
Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.
Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).
In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.
Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.
The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.
Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.
The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.
Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.
The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.
Overall results
The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).
The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).
At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).
The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).
There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.
The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.
Focus on grade 1-3a FL
Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.
Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.
Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.
The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.
The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.
“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.
This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.
Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.
NHL patients report fear, isolation during chemo
Patients undergoing chemotherapy for non-Hodgkin lymphoma (NHL) report feeling isolated and uncertain, and in some cases suicidal, according to a small qualitative study.
Daren Chircop, MS, and Josianne Scerri, PhD, of the University of Malta performed in-depth interviews with four men and two women with aggressive NHL who were midway through CHOP chemotherapy at a cancer center in Malta.
The findings, which were published in the European Journal of Oncology Nursing, highlight three overarching themes. Patients reported that they felt like they were living on an “emotional roller coaster, they were becoming dependent on others, and they were facing an uncertain future.
Specifically, being admitted to a hospital for chemotherapy brought on a fear of the unknown. While being released from the hospital caused anxiety about what would happen once they left the around-the-clock care of doctors and nurses.
The side effects of the chemotherapy – particularly fatigue – led to feelings of being dependent of others and a fear of becoming a burden to families, and even to nurses.
For four of the patients, who were not allowed to leave their hospital rooms during treatment, they reported feeling “imprisoned” and isolated.
Uncertainty was another common theme, with all of the patients reporting that they did not know if they would recover from their cancer and feeling that they had no control over the future.
Additionally, two of the patients experienced suicidal thoughts related to the side effects of treatment.
While many of these feelings are similar to reports by patients with other types of cancer, the researchers suggested that NHL patients experience a greater sense of isolation because they may not be able to leave their hospital rooms while undergoing chemotherapy due to a higher risk of infection.
“There is the need for ongoing psychological support to be available throughout the treatment period,” the researchers wrote. “Moreover, as NHL patients are affected both physically and emotionally whilst undergoing chemotherapy, the engagement of these individuals in some physical activity could be of benefit to them.”
There was no outside funding for the study and the researchers reported having no financial disclosures.
SOURCE: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.
Patients undergoing chemotherapy for non-Hodgkin lymphoma (NHL) report feeling isolated and uncertain, and in some cases suicidal, according to a small qualitative study.
Daren Chircop, MS, and Josianne Scerri, PhD, of the University of Malta performed in-depth interviews with four men and two women with aggressive NHL who were midway through CHOP chemotherapy at a cancer center in Malta.
The findings, which were published in the European Journal of Oncology Nursing, highlight three overarching themes. Patients reported that they felt like they were living on an “emotional roller coaster, they were becoming dependent on others, and they were facing an uncertain future.
Specifically, being admitted to a hospital for chemotherapy brought on a fear of the unknown. While being released from the hospital caused anxiety about what would happen once they left the around-the-clock care of doctors and nurses.
The side effects of the chemotherapy – particularly fatigue – led to feelings of being dependent of others and a fear of becoming a burden to families, and even to nurses.
For four of the patients, who were not allowed to leave their hospital rooms during treatment, they reported feeling “imprisoned” and isolated.
Uncertainty was another common theme, with all of the patients reporting that they did not know if they would recover from their cancer and feeling that they had no control over the future.
Additionally, two of the patients experienced suicidal thoughts related to the side effects of treatment.
While many of these feelings are similar to reports by patients with other types of cancer, the researchers suggested that NHL patients experience a greater sense of isolation because they may not be able to leave their hospital rooms while undergoing chemotherapy due to a higher risk of infection.
“There is the need for ongoing psychological support to be available throughout the treatment period,” the researchers wrote. “Moreover, as NHL patients are affected both physically and emotionally whilst undergoing chemotherapy, the engagement of these individuals in some physical activity could be of benefit to them.”
There was no outside funding for the study and the researchers reported having no financial disclosures.
SOURCE: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.
Patients undergoing chemotherapy for non-Hodgkin lymphoma (NHL) report feeling isolated and uncertain, and in some cases suicidal, according to a small qualitative study.
Daren Chircop, MS, and Josianne Scerri, PhD, of the University of Malta performed in-depth interviews with four men and two women with aggressive NHL who were midway through CHOP chemotherapy at a cancer center in Malta.
The findings, which were published in the European Journal of Oncology Nursing, highlight three overarching themes. Patients reported that they felt like they were living on an “emotional roller coaster, they were becoming dependent on others, and they were facing an uncertain future.
Specifically, being admitted to a hospital for chemotherapy brought on a fear of the unknown. While being released from the hospital caused anxiety about what would happen once they left the around-the-clock care of doctors and nurses.
The side effects of the chemotherapy – particularly fatigue – led to feelings of being dependent of others and a fear of becoming a burden to families, and even to nurses.
For four of the patients, who were not allowed to leave their hospital rooms during treatment, they reported feeling “imprisoned” and isolated.
Uncertainty was another common theme, with all of the patients reporting that they did not know if they would recover from their cancer and feeling that they had no control over the future.
Additionally, two of the patients experienced suicidal thoughts related to the side effects of treatment.
While many of these feelings are similar to reports by patients with other types of cancer, the researchers suggested that NHL patients experience a greater sense of isolation because they may not be able to leave their hospital rooms while undergoing chemotherapy due to a higher risk of infection.
“There is the need for ongoing psychological support to be available throughout the treatment period,” the researchers wrote. “Moreover, as NHL patients are affected both physically and emotionally whilst undergoing chemotherapy, the engagement of these individuals in some physical activity could be of benefit to them.”
There was no outside funding for the study and the researchers reported having no financial disclosures.
SOURCE: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.
FROM EUROPEAN JOURNAL OF ONCOLOGY NURSING
Key clinical point:
Major finding: Patients reported three themes while undergoing chemotherapy: living an emotional roller coaster, becoming dependent on others, and facing an uncertain future.
Study details: A qualitative study of six adults patients with non-Hodgkin lymphoma who were undergoing chemotherapy.
Disclosures: There was no outside funding for the study and the researchers reported having no financial disclosures.
Source: Chircop D et al. Eur J Oncol Nurs. 2018 Aug;35:117-21.