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SALT LAKE CITY – The combination of mycophenolate mofetil, tacrolimus, and posttransplant cyclophosphamide outperformed other prophylaxis regimens at reducing graft versus host disease with relapse-free survival in a multicenter trial.
The trial’s primary aim was to compare rates of post–hematopoietic stem cell transplant GVHD-free and relapse-free survival (GRFS) in the three study arms, compared with the tacrolimus/methotrexate group, who were receiving a “contemporary control,” Javier Bolaños-Meade, MD, said during a late-breaking abstract session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide group had a hazard ratio of 0.72 for reaching the primary endpoint – GRFS (95% confidence interval, 0.55-0.94; P = .04), compared with patients receiving the control regimen. In the study, GRFS was defined as the amount of time elapsed between transplant and any of: grade III-IV acute GVHD, chronic GVHD severe enough to require systemic therapy, disease relapse or progression, or death. Grade III-IV acute GVHD and GVHD survival were superior with mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide, compared with the control (P = .006 and .01, respectively).
The phase 2 trial enrolled adults aged 18-75 years who had a malignant disease and a matched donor, and were slated to receive reduced intensity conditioning. The study randomized patients 1:1:1 to one of three experimental regimens and 224 to the control tacrolimus/methotrexate regimen. In the experimental arms, 92 patients received mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide; 89 patients received tacrolimus/methotrexate/maraviroc, and 92 patients received tacrolimus/methotrexate/bortezomib.
“According to predetermined parameters for success, tacrolimus/mycophenolate mofetil/cyclophosphamide was superior to control in GRFS, severe acute GVHD, chronic GVHD requiring immunosuppression, and GVHD-free survival, without a negative impact on treatment-related mortality, relapse/progression, overall survival or disease-free survival,” Dr. Bolaños-Meade said.
Patients could be included in the study if they had acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome; patients with these diagnoses could have no circulating blasts and had to have less than 10% blasts in bone marrow. Patients with chronic lymphocytic leukemia and lymphoma with sensitive disease at the time of transplant were also eligible. All patients received peripheral blood stem cells, and underwent reduced intensity conditioning.
Permissible conditioning regimens included fludarabine/busulfan dosed at 8 mg/kg or less, fludarabine/cyclophosphamide with or without total body irradiation (TBI), fludarabine/TBI at 200 cGy, or fludarabine/melphalan dosed at less than 150 mg/m2 of body surface area. Alemtuzumab and anti-thymocyte globulin were not permitted.
Patients had to have a cardiac ejection fraction greater than 40%. For inclusion, patients had to have estimated creatinine clearance greater than 40 mL/min, bilirubin less than two times the upper limit of normal, and ALT/AST less than 2.5 times the upper limit of normal. Inclusion criteria also required adequate pulmonary function, defined as hemoglobin-corrected diffused capacity of carbon monoxide of at least 40% and forced expiratory volume in one second of 50% or greater.
Patients’ donors had to be either siblings, or 7/8 or 8/8 human leukocyte antigen-matched unrelated donors.
The patients receiving tacrolimus/methotrexate who served as controls were also collected prospectively, from centers that were not participating in the three-arm clinical trial. These patients also received reduced intensity conditioning and a peripheral blood stem cell transplant. This arm of the study was run through the Center for International Blood & Marrow Transplant Research. “I want to stress that the entry criteria were the same as for the intervention arms of the study,” Dr. Bolaños-Meade said.
Using a baseline rate of 23% for the GRFS endpoint, Dr. Bolaños-Meade and his collaborators established the size of the intervention and control arm so that the study would have 86%-88% power to detect a 20% improvement in the rate of GRFS over the contemporary control GVHD prophylaxis.
Across all study arms, patients were a median of 64 years old and most (58%-67%) were men. A little more than half of the patients had a Karnofsky Performance Status of 90%-100%. The Hematopoietic Cell Transplantation–Comorbidity Index was 3 or greater in about 40% of patients in the intervention arms, and in 62% of those in the control arm.
The phase 2 study was not designed to compare each experimental arm against the others, but only to compare each experimental arm to the control, said Dr. Bolaños-Meade, of the department of oncology at Johns Hopkins University, Baltimore.
“The comparisons that were made in this study ... have a limited power to really show superiority,” he said, adding that the National Clinical Trials Network is beginning a phase 3 trial that directly compares posttransplant cyclophosphamide to tacrolimus/methotrexate.
Dr. Bolaños-Meade reported serving on the data safety monitoring board of Incyte.
SOURCE: Bolaños-Meade J et al. 2018 BMT Tandem Meetings, Abstract LBA1.
SALT LAKE CITY – The combination of mycophenolate mofetil, tacrolimus, and posttransplant cyclophosphamide outperformed other prophylaxis regimens at reducing graft versus host disease with relapse-free survival in a multicenter trial.
The trial’s primary aim was to compare rates of post–hematopoietic stem cell transplant GVHD-free and relapse-free survival (GRFS) in the three study arms, compared with the tacrolimus/methotrexate group, who were receiving a “contemporary control,” Javier Bolaños-Meade, MD, said during a late-breaking abstract session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide group had a hazard ratio of 0.72 for reaching the primary endpoint – GRFS (95% confidence interval, 0.55-0.94; P = .04), compared with patients receiving the control regimen. In the study, GRFS was defined as the amount of time elapsed between transplant and any of: grade III-IV acute GVHD, chronic GVHD severe enough to require systemic therapy, disease relapse or progression, or death. Grade III-IV acute GVHD and GVHD survival were superior with mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide, compared with the control (P = .006 and .01, respectively).
The phase 2 trial enrolled adults aged 18-75 years who had a malignant disease and a matched donor, and were slated to receive reduced intensity conditioning. The study randomized patients 1:1:1 to one of three experimental regimens and 224 to the control tacrolimus/methotrexate regimen. In the experimental arms, 92 patients received mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide; 89 patients received tacrolimus/methotrexate/maraviroc, and 92 patients received tacrolimus/methotrexate/bortezomib.
“According to predetermined parameters for success, tacrolimus/mycophenolate mofetil/cyclophosphamide was superior to control in GRFS, severe acute GVHD, chronic GVHD requiring immunosuppression, and GVHD-free survival, without a negative impact on treatment-related mortality, relapse/progression, overall survival or disease-free survival,” Dr. Bolaños-Meade said.
Patients could be included in the study if they had acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome; patients with these diagnoses could have no circulating blasts and had to have less than 10% blasts in bone marrow. Patients with chronic lymphocytic leukemia and lymphoma with sensitive disease at the time of transplant were also eligible. All patients received peripheral blood stem cells, and underwent reduced intensity conditioning.
Permissible conditioning regimens included fludarabine/busulfan dosed at 8 mg/kg or less, fludarabine/cyclophosphamide with or without total body irradiation (TBI), fludarabine/TBI at 200 cGy, or fludarabine/melphalan dosed at less than 150 mg/m2 of body surface area. Alemtuzumab and anti-thymocyte globulin were not permitted.
Patients had to have a cardiac ejection fraction greater than 40%. For inclusion, patients had to have estimated creatinine clearance greater than 40 mL/min, bilirubin less than two times the upper limit of normal, and ALT/AST less than 2.5 times the upper limit of normal. Inclusion criteria also required adequate pulmonary function, defined as hemoglobin-corrected diffused capacity of carbon monoxide of at least 40% and forced expiratory volume in one second of 50% or greater.
Patients’ donors had to be either siblings, or 7/8 or 8/8 human leukocyte antigen-matched unrelated donors.
The patients receiving tacrolimus/methotrexate who served as controls were also collected prospectively, from centers that were not participating in the three-arm clinical trial. These patients also received reduced intensity conditioning and a peripheral blood stem cell transplant. This arm of the study was run through the Center for International Blood & Marrow Transplant Research. “I want to stress that the entry criteria were the same as for the intervention arms of the study,” Dr. Bolaños-Meade said.
Using a baseline rate of 23% for the GRFS endpoint, Dr. Bolaños-Meade and his collaborators established the size of the intervention and control arm so that the study would have 86%-88% power to detect a 20% improvement in the rate of GRFS over the contemporary control GVHD prophylaxis.
Across all study arms, patients were a median of 64 years old and most (58%-67%) were men. A little more than half of the patients had a Karnofsky Performance Status of 90%-100%. The Hematopoietic Cell Transplantation–Comorbidity Index was 3 or greater in about 40% of patients in the intervention arms, and in 62% of those in the control arm.
The phase 2 study was not designed to compare each experimental arm against the others, but only to compare each experimental arm to the control, said Dr. Bolaños-Meade, of the department of oncology at Johns Hopkins University, Baltimore.
“The comparisons that were made in this study ... have a limited power to really show superiority,” he said, adding that the National Clinical Trials Network is beginning a phase 3 trial that directly compares posttransplant cyclophosphamide to tacrolimus/methotrexate.
Dr. Bolaños-Meade reported serving on the data safety monitoring board of Incyte.
SOURCE: Bolaños-Meade J et al. 2018 BMT Tandem Meetings, Abstract LBA1.
SALT LAKE CITY – The combination of mycophenolate mofetil, tacrolimus, and posttransplant cyclophosphamide outperformed other prophylaxis regimens at reducing graft versus host disease with relapse-free survival in a multicenter trial.
The trial’s primary aim was to compare rates of post–hematopoietic stem cell transplant GVHD-free and relapse-free survival (GRFS) in the three study arms, compared with the tacrolimus/methotrexate group, who were receiving a “contemporary control,” Javier Bolaños-Meade, MD, said during a late-breaking abstract session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
The mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide group had a hazard ratio of 0.72 for reaching the primary endpoint – GRFS (95% confidence interval, 0.55-0.94; P = .04), compared with patients receiving the control regimen. In the study, GRFS was defined as the amount of time elapsed between transplant and any of: grade III-IV acute GVHD, chronic GVHD severe enough to require systemic therapy, disease relapse or progression, or death. Grade III-IV acute GVHD and GVHD survival were superior with mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide, compared with the control (P = .006 and .01, respectively).
The phase 2 trial enrolled adults aged 18-75 years who had a malignant disease and a matched donor, and were slated to receive reduced intensity conditioning. The study randomized patients 1:1:1 to one of three experimental regimens and 224 to the control tacrolimus/methotrexate regimen. In the experimental arms, 92 patients received mycophenolate mofetil/tacrolimus/posttransplant cyclophosphamide; 89 patients received tacrolimus/methotrexate/maraviroc, and 92 patients received tacrolimus/methotrexate/bortezomib.
“According to predetermined parameters for success, tacrolimus/mycophenolate mofetil/cyclophosphamide was superior to control in GRFS, severe acute GVHD, chronic GVHD requiring immunosuppression, and GVHD-free survival, without a negative impact on treatment-related mortality, relapse/progression, overall survival or disease-free survival,” Dr. Bolaños-Meade said.
Patients could be included in the study if they had acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome; patients with these diagnoses could have no circulating blasts and had to have less than 10% blasts in bone marrow. Patients with chronic lymphocytic leukemia and lymphoma with sensitive disease at the time of transplant were also eligible. All patients received peripheral blood stem cells, and underwent reduced intensity conditioning.
Permissible conditioning regimens included fludarabine/busulfan dosed at 8 mg/kg or less, fludarabine/cyclophosphamide with or without total body irradiation (TBI), fludarabine/TBI at 200 cGy, or fludarabine/melphalan dosed at less than 150 mg/m2 of body surface area. Alemtuzumab and anti-thymocyte globulin were not permitted.
Patients had to have a cardiac ejection fraction greater than 40%. For inclusion, patients had to have estimated creatinine clearance greater than 40 mL/min, bilirubin less than two times the upper limit of normal, and ALT/AST less than 2.5 times the upper limit of normal. Inclusion criteria also required adequate pulmonary function, defined as hemoglobin-corrected diffused capacity of carbon monoxide of at least 40% and forced expiratory volume in one second of 50% or greater.
Patients’ donors had to be either siblings, or 7/8 or 8/8 human leukocyte antigen-matched unrelated donors.
The patients receiving tacrolimus/methotrexate who served as controls were also collected prospectively, from centers that were not participating in the three-arm clinical trial. These patients also received reduced intensity conditioning and a peripheral blood stem cell transplant. This arm of the study was run through the Center for International Blood & Marrow Transplant Research. “I want to stress that the entry criteria were the same as for the intervention arms of the study,” Dr. Bolaños-Meade said.
Using a baseline rate of 23% for the GRFS endpoint, Dr. Bolaños-Meade and his collaborators established the size of the intervention and control arm so that the study would have 86%-88% power to detect a 20% improvement in the rate of GRFS over the contemporary control GVHD prophylaxis.
Across all study arms, patients were a median of 64 years old and most (58%-67%) were men. A little more than half of the patients had a Karnofsky Performance Status of 90%-100%. The Hematopoietic Cell Transplantation–Comorbidity Index was 3 or greater in about 40% of patients in the intervention arms, and in 62% of those in the control arm.
The phase 2 study was not designed to compare each experimental arm against the others, but only to compare each experimental arm to the control, said Dr. Bolaños-Meade, of the department of oncology at Johns Hopkins University, Baltimore.
“The comparisons that were made in this study ... have a limited power to really show superiority,” he said, adding that the National Clinical Trials Network is beginning a phase 3 trial that directly compares posttransplant cyclophosphamide to tacrolimus/methotrexate.
Dr. Bolaños-Meade reported serving on the data safety monitoring board of Incyte.
SOURCE: Bolaños-Meade J et al. 2018 BMT Tandem Meetings, Abstract LBA1.
REPORTING FROM THE 2018 BMT TANDEM MEETINGS
Key clinical point:
Major finding: The hazard ratio for GVHD-free and relapse-free survival was 0.72 for those receiving cyclophosphamide, compared with controls (P = .04).
Study details: Randomized, controlled trial of 497 patients receiving one of three intervention arm posttransplant regimens for GVHD prophylaxis, or a control regimen of tacrolimus and methotrexate.
Disclosures: Dr. Bolaños-Meade reported serving on the data safety monitoring board of Incyte.
Source: Bolaños-Meade J et al. 2018 BMT Tandem Meetings, Abstract LB1.