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Orelabrutinib could be ‘preferred’ BTK inhibitor for MCL
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
REPORTING FROM ASH 2019
The clinical impact of new approvals in sickle cell, MCL
In this edition of “How I Will Treat My Next Patient,” I highlight two recent drug approvals by the Food and Drug Administration – crizanlizumab for sickle cell patients with painful crises and zanubrutinib for mantle cell lymphoma (MCL) patients in relapse.
Crizanlizumab
P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on vessel walls and promotes firm attachment and extravasation to underlying tissues during inflammation. Up-regulation of P-selectin on endothelial cells and platelets contributes to the cell-cell interactions involved in the pathogenesis of sickle cell pain crises.
The SUSTAIN study was a multisite, placebo-controlled, randomized phase 2 trial of two different dosage levels of intravenous crizanlizumab (2.5 mg/kg or 5 mg/kg for 52 weeks), a humanized anti–P-selectin antibody, examining its effect on pain crises in patients with sickle cell disease. The primary endpoint was the annual rate of sickle cell pain crises, with a variety of clinically relevant secondary endpoints. The target population had 2-10 pain crises in the 12 months before enrollment. Patients on a stable dose of hydroxyurea for at least the most recent 3 months were allowed to enter, but if patients were not receiving hydroxyurea, it could not be initiated during the trial. Patients who were undergoing chronic red-cell transfusion therapy were excluded.
Among 198 enrolled patients, 35% did not complete the 52 weeks of treatment. Discontinuations were equally balanced among patients assigned to the high-dose, low-dose, and placebo cohorts. Adverse events associated with crizanlizumab included back pain, nausea, pyrexia, and arthralgia. Serious adverse events occurred in 55 patients, with 5 deaths, all of which were unrelated to treatment. Crizanlizumab did not augment hemolysis or bacterial infections.
In the efficacy analysis, patients receiving high-dose crizanlizumab had a median annual rate of 1.63 health care visits for sickle cell pain crises, compared with 2.98 visits for placebo patients (P = .01). In comparison with placebo, high-dose crizanlizumab also delayed the first pain crisis after starting treatment (4.1 months vs. 1.4 months), delayed the median time to a second pain crisis, and decreased the median number of pain crises annually.
More than twice as many high-dose crizanlizumab patients had no pain crisis episodes, compared with placebo patients. In general, differences were more striking in patients who were not taking hydroxyurea and who had non–hemoglobin SS disease. Differences in the primary endpoint between low-dose crizanlizumab and placebo were numerically, but not statistically, different.
How these results influence practice
It has been over 20 years since a new agent (hydroxyurea) was approved for sickle cell patients and, despite its use, sickle cell pain crises remain a frequent problem. Pain crises are associated with worse quality of life and increased risk of death. A promising advance is badly needed, especially in an era in which sensitivity to providers’ role in the opioid addiction crisis is highly scrutinized and may contribute to future undertreatment of pain episodes. This is especially true for patients from areas with high levels of opioid misuse.
The SUSTAIN trial was international, multi-institutional, placebo-controlled, and inclusive. These attributes enhance the likelihood that crizanlizumab will enhance patient care in routine practice. As an intravenous agent, monitoring adherence and toxicity are less challenging than with hydroxyurea. Despite these factors, however, there are some concerns. Crizanlizumab was not free of toxicity, quality of life via the Brief Pain Inventory used in the trial was not improved, and changes in the pain-severity and pain-interference domains were small. Treatment in SUSTAIN ensued for 52 weeks, so the emergence of late neutralizing antibodies and late toxicities with longer-term therapy will require careful postmarketing assessment.
These concerns notwithstanding, anyone who has cared for sickle cell patients would be excited about the potential benefits crizanlizumab could bring to patient care.
Zanubrutinib
The FDA has approved zanubrutinib for the treatment of MCL in adult patients who have received at least one prior therapy. The approval is based on the results of two studies in which overall response rate was the primary endpoint.
BGB-3111-206 (NCT03206970) was a phase 2, open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. BGB-3111-AU-003 (NCT 02343120) was a phase 1/2, open-label, dose-escalation trial of B-cell malignancies, including 32 previously treated MCL patients treated with zanubrutinib at 160 mg twice daily or 320 mg once daily.
In the phase 2 trial, 18fluorodeoxyglucose (FDG)–PET scans were required and the ORR was 84% (95% confidence interval, 74%-91%), with a complete response rate of 59% (95% CI, 48%-70%) and a median response duration of 19.5 months (95% CI, 16.6% to not estimable). In the phase 1/2 dose-escalation trial, FDG-PET scans were not required and the ORR was 84% (95% CI, 67%-95%), with a complete response rate of 22% (95% CI, 9%-40%) and a median response duration of 18.5 months (95% CI, 12.6% to not estimable). In both trials, median follow-up on study was about 18 months.
The most common adverse reactions were cytopenias, upper respiratory tract infection, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients. Of 118 MCL patients, 8 stopped therapy because of an adverse event, most frequently pneumonia (3.4%).
How these results influence practice
Unfortunately, the therapy of recurrent MCL is noncurative, because of the rapid development of treatment resistance. There are multiple single-and multiagent chemotherapy regimens that may be tried, many incorporating immunotherapy options such as anti-CD20- or Bruton tyrosine kinase (BTK)–targeted agents. Given the limited efficacy of these agents, temporary nature of remissions, and paucity of data comparing these various treatment options, participation in clinical trials is encouraged whenever possible.
Outside of a clinical trial, zanubrutinib joins ibrutinib and acalabrutinib as approved single-agent BTK inhibitors for adult MCL patients in relapse. The impressive ORR and response duration reported for zanubrutinib are similar to the results achieved with the other agents, but the toxicity pattern may be slightly different.
As in the treatment of hormonally sensitive breast cancer, clinicians and patients benefit when they have multiple similar, equally efficacious oral agents with slightly different toxicity patterns so that quality of life can be improved and treatment duration maximized before treatment resistance develops and a more toxic and/or inconvenient therapy needs to be employed.
Whether zanubrutinib has benefits beyond those for MCL patients in relapse will depend on the results of confirmatory trials and patient-reported outcome data.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I Will Treat My Next Patient,” I highlight two recent drug approvals by the Food and Drug Administration – crizanlizumab for sickle cell patients with painful crises and zanubrutinib for mantle cell lymphoma (MCL) patients in relapse.
Crizanlizumab
P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on vessel walls and promotes firm attachment and extravasation to underlying tissues during inflammation. Up-regulation of P-selectin on endothelial cells and platelets contributes to the cell-cell interactions involved in the pathogenesis of sickle cell pain crises.
The SUSTAIN study was a multisite, placebo-controlled, randomized phase 2 trial of two different dosage levels of intravenous crizanlizumab (2.5 mg/kg or 5 mg/kg for 52 weeks), a humanized anti–P-selectin antibody, examining its effect on pain crises in patients with sickle cell disease. The primary endpoint was the annual rate of sickle cell pain crises, with a variety of clinically relevant secondary endpoints. The target population had 2-10 pain crises in the 12 months before enrollment. Patients on a stable dose of hydroxyurea for at least the most recent 3 months were allowed to enter, but if patients were not receiving hydroxyurea, it could not be initiated during the trial. Patients who were undergoing chronic red-cell transfusion therapy were excluded.
Among 198 enrolled patients, 35% did not complete the 52 weeks of treatment. Discontinuations were equally balanced among patients assigned to the high-dose, low-dose, and placebo cohorts. Adverse events associated with crizanlizumab included back pain, nausea, pyrexia, and arthralgia. Serious adverse events occurred in 55 patients, with 5 deaths, all of which were unrelated to treatment. Crizanlizumab did not augment hemolysis or bacterial infections.
In the efficacy analysis, patients receiving high-dose crizanlizumab had a median annual rate of 1.63 health care visits for sickle cell pain crises, compared with 2.98 visits for placebo patients (P = .01). In comparison with placebo, high-dose crizanlizumab also delayed the first pain crisis after starting treatment (4.1 months vs. 1.4 months), delayed the median time to a second pain crisis, and decreased the median number of pain crises annually.
More than twice as many high-dose crizanlizumab patients had no pain crisis episodes, compared with placebo patients. In general, differences were more striking in patients who were not taking hydroxyurea and who had non–hemoglobin SS disease. Differences in the primary endpoint between low-dose crizanlizumab and placebo were numerically, but not statistically, different.
How these results influence practice
It has been over 20 years since a new agent (hydroxyurea) was approved for sickle cell patients and, despite its use, sickle cell pain crises remain a frequent problem. Pain crises are associated with worse quality of life and increased risk of death. A promising advance is badly needed, especially in an era in which sensitivity to providers’ role in the opioid addiction crisis is highly scrutinized and may contribute to future undertreatment of pain episodes. This is especially true for patients from areas with high levels of opioid misuse.
The SUSTAIN trial was international, multi-institutional, placebo-controlled, and inclusive. These attributes enhance the likelihood that crizanlizumab will enhance patient care in routine practice. As an intravenous agent, monitoring adherence and toxicity are less challenging than with hydroxyurea. Despite these factors, however, there are some concerns. Crizanlizumab was not free of toxicity, quality of life via the Brief Pain Inventory used in the trial was not improved, and changes in the pain-severity and pain-interference domains were small. Treatment in SUSTAIN ensued for 52 weeks, so the emergence of late neutralizing antibodies and late toxicities with longer-term therapy will require careful postmarketing assessment.
These concerns notwithstanding, anyone who has cared for sickle cell patients would be excited about the potential benefits crizanlizumab could bring to patient care.
Zanubrutinib
The FDA has approved zanubrutinib for the treatment of MCL in adult patients who have received at least one prior therapy. The approval is based on the results of two studies in which overall response rate was the primary endpoint.
BGB-3111-206 (NCT03206970) was a phase 2, open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. BGB-3111-AU-003 (NCT 02343120) was a phase 1/2, open-label, dose-escalation trial of B-cell malignancies, including 32 previously treated MCL patients treated with zanubrutinib at 160 mg twice daily or 320 mg once daily.
In the phase 2 trial, 18fluorodeoxyglucose (FDG)–PET scans were required and the ORR was 84% (95% confidence interval, 74%-91%), with a complete response rate of 59% (95% CI, 48%-70%) and a median response duration of 19.5 months (95% CI, 16.6% to not estimable). In the phase 1/2 dose-escalation trial, FDG-PET scans were not required and the ORR was 84% (95% CI, 67%-95%), with a complete response rate of 22% (95% CI, 9%-40%) and a median response duration of 18.5 months (95% CI, 12.6% to not estimable). In both trials, median follow-up on study was about 18 months.
The most common adverse reactions were cytopenias, upper respiratory tract infection, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients. Of 118 MCL patients, 8 stopped therapy because of an adverse event, most frequently pneumonia (3.4%).
How these results influence practice
Unfortunately, the therapy of recurrent MCL is noncurative, because of the rapid development of treatment resistance. There are multiple single-and multiagent chemotherapy regimens that may be tried, many incorporating immunotherapy options such as anti-CD20- or Bruton tyrosine kinase (BTK)–targeted agents. Given the limited efficacy of these agents, temporary nature of remissions, and paucity of data comparing these various treatment options, participation in clinical trials is encouraged whenever possible.
Outside of a clinical trial, zanubrutinib joins ibrutinib and acalabrutinib as approved single-agent BTK inhibitors for adult MCL patients in relapse. The impressive ORR and response duration reported for zanubrutinib are similar to the results achieved with the other agents, but the toxicity pattern may be slightly different.
As in the treatment of hormonally sensitive breast cancer, clinicians and patients benefit when they have multiple similar, equally efficacious oral agents with slightly different toxicity patterns so that quality of life can be improved and treatment duration maximized before treatment resistance develops and a more toxic and/or inconvenient therapy needs to be employed.
Whether zanubrutinib has benefits beyond those for MCL patients in relapse will depend on the results of confirmatory trials and patient-reported outcome data.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I Will Treat My Next Patient,” I highlight two recent drug approvals by the Food and Drug Administration – crizanlizumab for sickle cell patients with painful crises and zanubrutinib for mantle cell lymphoma (MCL) patients in relapse.
Crizanlizumab
P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on vessel walls and promotes firm attachment and extravasation to underlying tissues during inflammation. Up-regulation of P-selectin on endothelial cells and platelets contributes to the cell-cell interactions involved in the pathogenesis of sickle cell pain crises.
The SUSTAIN study was a multisite, placebo-controlled, randomized phase 2 trial of two different dosage levels of intravenous crizanlizumab (2.5 mg/kg or 5 mg/kg for 52 weeks), a humanized anti–P-selectin antibody, examining its effect on pain crises in patients with sickle cell disease. The primary endpoint was the annual rate of sickle cell pain crises, with a variety of clinically relevant secondary endpoints. The target population had 2-10 pain crises in the 12 months before enrollment. Patients on a stable dose of hydroxyurea for at least the most recent 3 months were allowed to enter, but if patients were not receiving hydroxyurea, it could not be initiated during the trial. Patients who were undergoing chronic red-cell transfusion therapy were excluded.
Among 198 enrolled patients, 35% did not complete the 52 weeks of treatment. Discontinuations were equally balanced among patients assigned to the high-dose, low-dose, and placebo cohorts. Adverse events associated with crizanlizumab included back pain, nausea, pyrexia, and arthralgia. Serious adverse events occurred in 55 patients, with 5 deaths, all of which were unrelated to treatment. Crizanlizumab did not augment hemolysis or bacterial infections.
In the efficacy analysis, patients receiving high-dose crizanlizumab had a median annual rate of 1.63 health care visits for sickle cell pain crises, compared with 2.98 visits for placebo patients (P = .01). In comparison with placebo, high-dose crizanlizumab also delayed the first pain crisis after starting treatment (4.1 months vs. 1.4 months), delayed the median time to a second pain crisis, and decreased the median number of pain crises annually.
More than twice as many high-dose crizanlizumab patients had no pain crisis episodes, compared with placebo patients. In general, differences were more striking in patients who were not taking hydroxyurea and who had non–hemoglobin SS disease. Differences in the primary endpoint between low-dose crizanlizumab and placebo were numerically, but not statistically, different.
How these results influence practice
It has been over 20 years since a new agent (hydroxyurea) was approved for sickle cell patients and, despite its use, sickle cell pain crises remain a frequent problem. Pain crises are associated with worse quality of life and increased risk of death. A promising advance is badly needed, especially in an era in which sensitivity to providers’ role in the opioid addiction crisis is highly scrutinized and may contribute to future undertreatment of pain episodes. This is especially true for patients from areas with high levels of opioid misuse.
The SUSTAIN trial was international, multi-institutional, placebo-controlled, and inclusive. These attributes enhance the likelihood that crizanlizumab will enhance patient care in routine practice. As an intravenous agent, monitoring adherence and toxicity are less challenging than with hydroxyurea. Despite these factors, however, there are some concerns. Crizanlizumab was not free of toxicity, quality of life via the Brief Pain Inventory used in the trial was not improved, and changes in the pain-severity and pain-interference domains were small. Treatment in SUSTAIN ensued for 52 weeks, so the emergence of late neutralizing antibodies and late toxicities with longer-term therapy will require careful postmarketing assessment.
These concerns notwithstanding, anyone who has cared for sickle cell patients would be excited about the potential benefits crizanlizumab could bring to patient care.
Zanubrutinib
The FDA has approved zanubrutinib for the treatment of MCL in adult patients who have received at least one prior therapy. The approval is based on the results of two studies in which overall response rate was the primary endpoint.
BGB-3111-206 (NCT03206970) was a phase 2, open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. BGB-3111-AU-003 (NCT 02343120) was a phase 1/2, open-label, dose-escalation trial of B-cell malignancies, including 32 previously treated MCL patients treated with zanubrutinib at 160 mg twice daily or 320 mg once daily.
In the phase 2 trial, 18fluorodeoxyglucose (FDG)–PET scans were required and the ORR was 84% (95% confidence interval, 74%-91%), with a complete response rate of 59% (95% CI, 48%-70%) and a median response duration of 19.5 months (95% CI, 16.6% to not estimable). In the phase 1/2 dose-escalation trial, FDG-PET scans were not required and the ORR was 84% (95% CI, 67%-95%), with a complete response rate of 22% (95% CI, 9%-40%) and a median response duration of 18.5 months (95% CI, 12.6% to not estimable). In both trials, median follow-up on study was about 18 months.
The most common adverse reactions were cytopenias, upper respiratory tract infection, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients. Of 118 MCL patients, 8 stopped therapy because of an adverse event, most frequently pneumonia (3.4%).
How these results influence practice
Unfortunately, the therapy of recurrent MCL is noncurative, because of the rapid development of treatment resistance. There are multiple single-and multiagent chemotherapy regimens that may be tried, many incorporating immunotherapy options such as anti-CD20- or Bruton tyrosine kinase (BTK)–targeted agents. Given the limited efficacy of these agents, temporary nature of remissions, and paucity of data comparing these various treatment options, participation in clinical trials is encouraged whenever possible.
Outside of a clinical trial, zanubrutinib joins ibrutinib and acalabrutinib as approved single-agent BTK inhibitors for adult MCL patients in relapse. The impressive ORR and response duration reported for zanubrutinib are similar to the results achieved with the other agents, but the toxicity pattern may be slightly different.
As in the treatment of hormonally sensitive breast cancer, clinicians and patients benefit when they have multiple similar, equally efficacious oral agents with slightly different toxicity patterns so that quality of life can be improved and treatment duration maximized before treatment resistance develops and a more toxic and/or inconvenient therapy needs to be employed.
Whether zanubrutinib has benefits beyond those for MCL patients in relapse will depend on the results of confirmatory trials and patient-reported outcome data.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
SOX11 shows value as diagnostic marker in MCL
SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.
Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.
The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.
The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.
“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”
With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.
“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.
The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.
SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.
SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.
Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.
The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.
The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.
“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”
With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.
“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.
The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.
SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.
SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.
Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.
The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.
The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.
“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”
With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.
“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.
The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.
SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.
FROM PLOS ONE
Acalabrutinib may outperform other targeted therapies in MCL
For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.
Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).
Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.
“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.
To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.
Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.
There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.
The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.
Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.
“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.
The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.
SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .
For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.
Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).
Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.
“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.
To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.
Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.
There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.
The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.
Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.
“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.
The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.
SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .
For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.
Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).
Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.
“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.
To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.
Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.
There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.
The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.
Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.
“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.
The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.
SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .
FROM CLINICAL THERAPEUTICS
FDA approves Brukinsa for relapsed, refractory MCL
The Food and Drug Administration has approved zanubrutinib (Brukinsa) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.
The approval is based on results from two separate studies; in a global phase 1/2 trial, patients with relapsed or refractory MCL who received zanubrutinib had an overall response rate of 84%, with 22% experiencing a complete response and 62% experiencing partial response. Median duration of response was 18.5 months. The ORR in the second study – a multicenter phase 2 trial – was also 84%, but with 59% experiencing a complete response and 24% experiencing partial response; duration of response was 19.5 months.
The most common adverse events reported during the trials were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, hematuria, fatigue, constipation, and hemorrhage. The most common serious adverse events were pneumonia and hemorrhage.
Of the 118 patients with MCL treated with zanubrutinib over the two trials, 8 had to be discontinued because of adverse events.
The recommended dose of zanubrutinib is 320 mg, taken orally 160 mg twice daily or 320 mg once daily, with or without food.
“BTK [Bruton kinase] inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL,” Luhua (Michael) Wang, MD, clinical trial investigator and professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, said in a statement.
The Food and Drug Administration has approved zanubrutinib (Brukinsa) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.
The approval is based on results from two separate studies; in a global phase 1/2 trial, patients with relapsed or refractory MCL who received zanubrutinib had an overall response rate of 84%, with 22% experiencing a complete response and 62% experiencing partial response. Median duration of response was 18.5 months. The ORR in the second study – a multicenter phase 2 trial – was also 84%, but with 59% experiencing a complete response and 24% experiencing partial response; duration of response was 19.5 months.
The most common adverse events reported during the trials were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, hematuria, fatigue, constipation, and hemorrhage. The most common serious adverse events were pneumonia and hemorrhage.
Of the 118 patients with MCL treated with zanubrutinib over the two trials, 8 had to be discontinued because of adverse events.
The recommended dose of zanubrutinib is 320 mg, taken orally 160 mg twice daily or 320 mg once daily, with or without food.
“BTK [Bruton kinase] inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL,” Luhua (Michael) Wang, MD, clinical trial investigator and professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, said in a statement.
The Food and Drug Administration has approved zanubrutinib (Brukinsa) for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.
The approval is based on results from two separate studies; in a global phase 1/2 trial, patients with relapsed or refractory MCL who received zanubrutinib had an overall response rate of 84%, with 22% experiencing a complete response and 62% experiencing partial response. Median duration of response was 18.5 months. The ORR in the second study – a multicenter phase 2 trial – was also 84%, but with 59% experiencing a complete response and 24% experiencing partial response; duration of response was 19.5 months.
The most common adverse events reported during the trials were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, hematuria, fatigue, constipation, and hemorrhage. The most common serious adverse events were pneumonia and hemorrhage.
Of the 118 patients with MCL treated with zanubrutinib over the two trials, 8 had to be discontinued because of adverse events.
The recommended dose of zanubrutinib is 320 mg, taken orally 160 mg twice daily or 320 mg once daily, with or without food.
“BTK [Bruton kinase] inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL,” Luhua (Michael) Wang, MD, clinical trial investigator and professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, said in a statement.
Survival ‘excellent’ after rituximab-bendamustine induction in transplant-eligible MCL
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.
The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.
By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.
“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.
The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.
In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.
The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.
Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.
With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.
The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.
MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.
In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.
The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.
SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.
FROM BLOOD ADVANCES
ASCO to award $50,000 young investigator grant to study MCL
Early-career researchers who are interested in studying
The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.
The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.
Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.
The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.
The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.
Application instructions are available on the ASCO website.
Early-career researchers who are interested in studying
The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.
The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.
Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.
The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.
The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.
Application instructions are available on the ASCO website.
Early-career researchers who are interested in studying
The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.
The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.
Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.
The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.
The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.
Application instructions are available on the ASCO website.
Follow-up shows favorable results with acalabrutinib in MCL
Acalabrutinib monotherapy can produce durable responses in relapsed/refractory mantle cell lymphoma (MCL), according to updated results from a phase 2 trial.
The drug produced an overall response rate (ORR) of 81%, and the median duration of response was 26 months.
These are the highest such figures reported “among all approved single-agent therapies for the treatment of relapsed/refractory MCL,” Michael Wang, MD, of the MD Anderson Cancer Center at the University of Texas in Houston and colleagues wrote in a letter in Leukemia.
Dr. Wang and colleagues reported updated results in 124 patients treated on the ACE-LY-004 trial. At baseline, the patients had a median age of 68 years (range, 42-90 years), and 80% were men. Three-quarters of patients had stage IV disease, 72% had extranodal disease, 21% had blastoid/pleomorphic MCL, and 26% had a Ki-67 proliferation index of 50% or greater.
At a median follow-up of 26 months, 40% (n = 49) of patients were still on acalabrutinib, and 61% (n = 76) were still in follow-up for survival. Six patients went on to allogeneic transplant at a median of 19 days after stopping acalabrutinib.
The ORR was 81% (100/124), and the complete response (CR) rate was 43% (n = 53). Four patients who initially had a partial response converted to a CR with longer follow-up. The estimated 24-month duration of response was 52.4%.
“ORR was consistent across patients with refractory disease and those with blastoid/pleomorphic MCL, despite those patients having a higher mean Ki-67 index [of 50% or greater], suggesting that some patients with poorer prognosis may also benefit from acalabrutinib,” Dr. Wang and colleagues wrote.
There were 29 patients evaluable for minimal residual disease (MRD) assessment. Seven patients (24%) had MRD-negative disease in the peripheral blood after they achieved a CR. An additional patient with a CR became MRD negative when a second blood sample was taken about 6 months after the first.
“Despite limited samples, these results demonstrate that continued use of acalabrutinib can lead to undetectable MRD in patients with CR,” Dr. Wang and his colleagues wrote. “Since most patients with MRD data are still on treatment (27/29), relationships between MRD negativity and durability of response cannot be made at this time.”
The median progression-free survival was 20 months, and the median overall survival was not reached. The estimated 24-month progression-free survival rate was 49.0%, and the estimated 24-month overall survival rate was 72.4%. Patients with low/intermediate Mantle Cell Lymphoma International Prognostic Index scores, classical MCL, and a Ki-67 index less than 50% had a longer duration of response and survival.
The adverse event profile was “largely consistent with earlier reporting,” Dr. Wang and colleagues wrote. The most frequent adverse events were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). The most common grade 3/4 adverse events were anemia (10%), neutropenia (10%), and pneumonia (6%).
Ten patients developed second primary cancers. There were no new atrial fibrillation events and no new hypertension events. The frequency of infections decreased over time, as did the number of bleeding events. However, two of three major hemorrhage events occurred after the previous report was published.
There were 43 deaths (35%), 29 of them because of disease progression. Six patients died of adverse events, two died of unknown causes, and two died of secondary acute myeloid leukemia. Other causes of death included multiorgan failure, intestinal obstruction, lung cancer, and graft-versus-host disease.
This study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. The researchers reported relationships with AstraZeneca/Acerta Pharma and many other companies.
SOURCE: Wang M et al. Leukemia. 2019 Sep 26. doi: 10.1038/s41375-019-0575-9.
Acalabrutinib monotherapy can produce durable responses in relapsed/refractory mantle cell lymphoma (MCL), according to updated results from a phase 2 trial.
The drug produced an overall response rate (ORR) of 81%, and the median duration of response was 26 months.
These are the highest such figures reported “among all approved single-agent therapies for the treatment of relapsed/refractory MCL,” Michael Wang, MD, of the MD Anderson Cancer Center at the University of Texas in Houston and colleagues wrote in a letter in Leukemia.
Dr. Wang and colleagues reported updated results in 124 patients treated on the ACE-LY-004 trial. At baseline, the patients had a median age of 68 years (range, 42-90 years), and 80% were men. Three-quarters of patients had stage IV disease, 72% had extranodal disease, 21% had blastoid/pleomorphic MCL, and 26% had a Ki-67 proliferation index of 50% or greater.
At a median follow-up of 26 months, 40% (n = 49) of patients were still on acalabrutinib, and 61% (n = 76) were still in follow-up for survival. Six patients went on to allogeneic transplant at a median of 19 days after stopping acalabrutinib.
The ORR was 81% (100/124), and the complete response (CR) rate was 43% (n = 53). Four patients who initially had a partial response converted to a CR with longer follow-up. The estimated 24-month duration of response was 52.4%.
“ORR was consistent across patients with refractory disease and those with blastoid/pleomorphic MCL, despite those patients having a higher mean Ki-67 index [of 50% or greater], suggesting that some patients with poorer prognosis may also benefit from acalabrutinib,” Dr. Wang and colleagues wrote.
There were 29 patients evaluable for minimal residual disease (MRD) assessment. Seven patients (24%) had MRD-negative disease in the peripheral blood after they achieved a CR. An additional patient with a CR became MRD negative when a second blood sample was taken about 6 months after the first.
“Despite limited samples, these results demonstrate that continued use of acalabrutinib can lead to undetectable MRD in patients with CR,” Dr. Wang and his colleagues wrote. “Since most patients with MRD data are still on treatment (27/29), relationships between MRD negativity and durability of response cannot be made at this time.”
The median progression-free survival was 20 months, and the median overall survival was not reached. The estimated 24-month progression-free survival rate was 49.0%, and the estimated 24-month overall survival rate was 72.4%. Patients with low/intermediate Mantle Cell Lymphoma International Prognostic Index scores, classical MCL, and a Ki-67 index less than 50% had a longer duration of response and survival.
The adverse event profile was “largely consistent with earlier reporting,” Dr. Wang and colleagues wrote. The most frequent adverse events were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). The most common grade 3/4 adverse events were anemia (10%), neutropenia (10%), and pneumonia (6%).
Ten patients developed second primary cancers. There were no new atrial fibrillation events and no new hypertension events. The frequency of infections decreased over time, as did the number of bleeding events. However, two of three major hemorrhage events occurred after the previous report was published.
There were 43 deaths (35%), 29 of them because of disease progression. Six patients died of adverse events, two died of unknown causes, and two died of secondary acute myeloid leukemia. Other causes of death included multiorgan failure, intestinal obstruction, lung cancer, and graft-versus-host disease.
This study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. The researchers reported relationships with AstraZeneca/Acerta Pharma and many other companies.
SOURCE: Wang M et al. Leukemia. 2019 Sep 26. doi: 10.1038/s41375-019-0575-9.
Acalabrutinib monotherapy can produce durable responses in relapsed/refractory mantle cell lymphoma (MCL), according to updated results from a phase 2 trial.
The drug produced an overall response rate (ORR) of 81%, and the median duration of response was 26 months.
These are the highest such figures reported “among all approved single-agent therapies for the treatment of relapsed/refractory MCL,” Michael Wang, MD, of the MD Anderson Cancer Center at the University of Texas in Houston and colleagues wrote in a letter in Leukemia.
Dr. Wang and colleagues reported updated results in 124 patients treated on the ACE-LY-004 trial. At baseline, the patients had a median age of 68 years (range, 42-90 years), and 80% were men. Three-quarters of patients had stage IV disease, 72% had extranodal disease, 21% had blastoid/pleomorphic MCL, and 26% had a Ki-67 proliferation index of 50% or greater.
At a median follow-up of 26 months, 40% (n = 49) of patients were still on acalabrutinib, and 61% (n = 76) were still in follow-up for survival. Six patients went on to allogeneic transplant at a median of 19 days after stopping acalabrutinib.
The ORR was 81% (100/124), and the complete response (CR) rate was 43% (n = 53). Four patients who initially had a partial response converted to a CR with longer follow-up. The estimated 24-month duration of response was 52.4%.
“ORR was consistent across patients with refractory disease and those with blastoid/pleomorphic MCL, despite those patients having a higher mean Ki-67 index [of 50% or greater], suggesting that some patients with poorer prognosis may also benefit from acalabrutinib,” Dr. Wang and colleagues wrote.
There were 29 patients evaluable for minimal residual disease (MRD) assessment. Seven patients (24%) had MRD-negative disease in the peripheral blood after they achieved a CR. An additional patient with a CR became MRD negative when a second blood sample was taken about 6 months after the first.
“Despite limited samples, these results demonstrate that continued use of acalabrutinib can lead to undetectable MRD in patients with CR,” Dr. Wang and his colleagues wrote. “Since most patients with MRD data are still on treatment (27/29), relationships between MRD negativity and durability of response cannot be made at this time.”
The median progression-free survival was 20 months, and the median overall survival was not reached. The estimated 24-month progression-free survival rate was 49.0%, and the estimated 24-month overall survival rate was 72.4%. Patients with low/intermediate Mantle Cell Lymphoma International Prognostic Index scores, classical MCL, and a Ki-67 index less than 50% had a longer duration of response and survival.
The adverse event profile was “largely consistent with earlier reporting,” Dr. Wang and colleagues wrote. The most frequent adverse events were headache (38%), diarrhea (36%), fatigue (28%), cough (22%), and myalgia (21%). The most common grade 3/4 adverse events were anemia (10%), neutropenia (10%), and pneumonia (6%).
Ten patients developed second primary cancers. There were no new atrial fibrillation events and no new hypertension events. The frequency of infections decreased over time, as did the number of bleeding events. However, two of three major hemorrhage events occurred after the previous report was published.
There were 43 deaths (35%), 29 of them because of disease progression. Six patients died of adverse events, two died of unknown causes, and two died of secondary acute myeloid leukemia. Other causes of death included multiorgan failure, intestinal obstruction, lung cancer, and graft-versus-host disease.
This study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. The researchers reported relationships with AstraZeneca/Acerta Pharma and many other companies.
SOURCE: Wang M et al. Leukemia. 2019 Sep 26. doi: 10.1038/s41375-019-0575-9.
FROM LEUKEMIA
Staging PET/CT better defines extent of mantle cell lymphoma
Use of staging PET/CT better defines the extent of mantle cell lymphoma (MCL) in certain compartments, adding important information for treatment decisions, a cohort study suggests. However, patient selection and evaluation criteria are important for its utility.
“A correct and early identification of initial disease could be crucial because it could affect patient management and therapeutic choice,” Domenico Albano, MD, a nuclear medicine physician at the University of Brescia (Italy) and Spedali Civili Brescia, and colleagues wrote in Clinical Lymphoma, Myeloma, & Leukemia.
Using retrospective data from two centers and 122 patients with MCL, the investigators compared the utility of staging 18F-fluorodeoxyglucose (18F-FDG) PET/CT with that of other modalities used for detecting disease in specific compartments. They also assessed its impact on patient management.
The study results showed that, with the exception of a single patient having bone marrow involvement, all patients had positive PET/CT results, with detection of at least one hypermetabolic lesion.
For assessing nodal involvement, compared with CT alone, PET/CT detected additional lesions in 21% of patients. Splenic lesions were detected by PET/CT in 49% of patients and by CT alone in 47%.
For assessing bone marrow involvement, compared with bone marrow biopsy, PET/CT had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 97%, a negative predictive value of 65%, and an overall accuracy of 74%.
For gastrointestinal involvement, compared with endoscopy, PET/CT had a sensitivity of 64% (78% after excluding diabetic patients taking metformin), a specificity of 91% (92%), a positive predictive value of 69% (72%), a negative predictive value of 90% (94%), and an overall accuracy of 85% (89%).
Ultimately, relative to CT alone, PET/CT altered stage and management in 19% of patients. Specifically, this imaging led to up-staging in 17% of patients, prompting clinicians to switch to more-aggressive chemotherapy, and down-staging in 2% of patients, prompting clinicians to skip unnecessary invasive therapies.
“We demonstrated that 18F-FDG pathologic uptake in MCL occurred in almost all patients, with excellent detection rate in nodal and splenic disease – indeed, better than CT,” the researchers wrote. “When we analyzed bone marrow and gastrointestinal involvement, the selection of patients excluding all conditions potentially affecting organ uptake and the use of specific criteria for the evaluation of these organs seemed to be crucial. Within these caveats, PET/CT showed good specificity for bone marrow and gastrointestinal evaluation.”
Study funding was not disclosed. Dr. Albano reported having no relevant conflicts of interest.
SOURCE: Albano D et al. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e457-64.
Use of staging PET/CT better defines the extent of mantle cell lymphoma (MCL) in certain compartments, adding important information for treatment decisions, a cohort study suggests. However, patient selection and evaluation criteria are important for its utility.
“A correct and early identification of initial disease could be crucial because it could affect patient management and therapeutic choice,” Domenico Albano, MD, a nuclear medicine physician at the University of Brescia (Italy) and Spedali Civili Brescia, and colleagues wrote in Clinical Lymphoma, Myeloma, & Leukemia.
Using retrospective data from two centers and 122 patients with MCL, the investigators compared the utility of staging 18F-fluorodeoxyglucose (18F-FDG) PET/CT with that of other modalities used for detecting disease in specific compartments. They also assessed its impact on patient management.
The study results showed that, with the exception of a single patient having bone marrow involvement, all patients had positive PET/CT results, with detection of at least one hypermetabolic lesion.
For assessing nodal involvement, compared with CT alone, PET/CT detected additional lesions in 21% of patients. Splenic lesions were detected by PET/CT in 49% of patients and by CT alone in 47%.
For assessing bone marrow involvement, compared with bone marrow biopsy, PET/CT had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 97%, a negative predictive value of 65%, and an overall accuracy of 74%.
For gastrointestinal involvement, compared with endoscopy, PET/CT had a sensitivity of 64% (78% after excluding diabetic patients taking metformin), a specificity of 91% (92%), a positive predictive value of 69% (72%), a negative predictive value of 90% (94%), and an overall accuracy of 85% (89%).
Ultimately, relative to CT alone, PET/CT altered stage and management in 19% of patients. Specifically, this imaging led to up-staging in 17% of patients, prompting clinicians to switch to more-aggressive chemotherapy, and down-staging in 2% of patients, prompting clinicians to skip unnecessary invasive therapies.
“We demonstrated that 18F-FDG pathologic uptake in MCL occurred in almost all patients, with excellent detection rate in nodal and splenic disease – indeed, better than CT,” the researchers wrote. “When we analyzed bone marrow and gastrointestinal involvement, the selection of patients excluding all conditions potentially affecting organ uptake and the use of specific criteria for the evaluation of these organs seemed to be crucial. Within these caveats, PET/CT showed good specificity for bone marrow and gastrointestinal evaluation.”
Study funding was not disclosed. Dr. Albano reported having no relevant conflicts of interest.
SOURCE: Albano D et al. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e457-64.
Use of staging PET/CT better defines the extent of mantle cell lymphoma (MCL) in certain compartments, adding important information for treatment decisions, a cohort study suggests. However, patient selection and evaluation criteria are important for its utility.
“A correct and early identification of initial disease could be crucial because it could affect patient management and therapeutic choice,” Domenico Albano, MD, a nuclear medicine physician at the University of Brescia (Italy) and Spedali Civili Brescia, and colleagues wrote in Clinical Lymphoma, Myeloma, & Leukemia.
Using retrospective data from two centers and 122 patients with MCL, the investigators compared the utility of staging 18F-fluorodeoxyglucose (18F-FDG) PET/CT with that of other modalities used for detecting disease in specific compartments. They also assessed its impact on patient management.
The study results showed that, with the exception of a single patient having bone marrow involvement, all patients had positive PET/CT results, with detection of at least one hypermetabolic lesion.
For assessing nodal involvement, compared with CT alone, PET/CT detected additional lesions in 21% of patients. Splenic lesions were detected by PET/CT in 49% of patients and by CT alone in 47%.
For assessing bone marrow involvement, compared with bone marrow biopsy, PET/CT had a sensitivity of 52%, a specificity of 98%, a positive predictive value of 97%, a negative predictive value of 65%, and an overall accuracy of 74%.
For gastrointestinal involvement, compared with endoscopy, PET/CT had a sensitivity of 64% (78% after excluding diabetic patients taking metformin), a specificity of 91% (92%), a positive predictive value of 69% (72%), a negative predictive value of 90% (94%), and an overall accuracy of 85% (89%).
Ultimately, relative to CT alone, PET/CT altered stage and management in 19% of patients. Specifically, this imaging led to up-staging in 17% of patients, prompting clinicians to switch to more-aggressive chemotherapy, and down-staging in 2% of patients, prompting clinicians to skip unnecessary invasive therapies.
“We demonstrated that 18F-FDG pathologic uptake in MCL occurred in almost all patients, with excellent detection rate in nodal and splenic disease – indeed, better than CT,” the researchers wrote. “When we analyzed bone marrow and gastrointestinal involvement, the selection of patients excluding all conditions potentially affecting organ uptake and the use of specific criteria for the evaluation of these organs seemed to be crucial. Within these caveats, PET/CT showed good specificity for bone marrow and gastrointestinal evaluation.”
Study funding was not disclosed. Dr. Albano reported having no relevant conflicts of interest.
SOURCE: Albano D et al. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e457-64.
FROM CLINICAL LYMPHOMA, MYELOMA, & LEUKEMIA
Rituximab, bendamustine look better than chemo alone in MCL
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
In older patients with newly diagnosed mantle cell lymphoma (MCL), first-line therapy with rituximab- and bendamustine-based regimens significantly reduced 1-year mortality rates versus chemotherapy alone, according to a retrospective analysis.
“This study evaluated the comparative effectiveness of [rituximab, bortezomib, or bendamustine] in elderly patients newly diagnosed with MCL,” wrote Shuangshuang Fu, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. The findings were reported in Clinical Lymphoma, Myeloma & Leukemia.
The researchers studied population-based data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. They identified all patients over age 65 years who received a new diagnosis of MCL between Jan. 1, 1999, and Dec. 31, 2013.
The study cohort included a total of 1,215 patients. Participants were classified into four different groups according to treatment regimen: chemotherapy alone, rituximab plus or minus chemotherapy, bendamustine plus or minus chemotherapy, and bortezomib plus or minus chemotherapy.
At 1-year follow-up, the team analyzed various mortality outcomes, including MCL-specific, all-cause, and noncancer mortality. The bortezomib results were not included in the primary analysis because of small sample size, according to the researchers.
After multivariable analysis, Dr. Fu and colleagues found that 1-year all-cause mortality rate was significantly lower for patients receiving rituximab-based regimens, compared with chemotherapy alone (hazard ratio, 0.38; 95% confidence interval, 0.25-0.59). There was a similar decline for MCL-specific mortality (HR, 0.38; 95% CI, 0.24-0.60).
The 1-year MCL-specific mortality was also significantly reduced in the bendamustine group, compared with chemotherapy alone (HR, 0.49; 95% CI, 0.24-0.99).
“Our findings comparing rituximab with chemotherapy alone further confirmed the benefit of adding rituximab to chemotherapy in newly diagnosed older MCL patients,” they wrote.
The researchers acknowledged that a key limitation of the study was the observational design. As a result, selection bias and unmeasured confounding could have influenced the results.
“Future studies evaluating the comparative effectiveness of those newly approved novel agents for MCL patients were warranted as more data are available,” they concluded.
The study was funded by the Duncan Family Institute, the Cancer Prevention Research Institute of Texas, and the National Institutes of Health. The authors reported having no conflicts of interest.
SOURCE: Fu S et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 30. doi: 10.1016/j.clml.2019.08.014.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA