Javier Bolaños Meade
SALT LAKE CITY — Adults treated with mycophenolate mofetil and tacrolimus plus cyclophosphamide after allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning had superior graft-versus-host disease-related outcomes compared with other novel approaches, according to late-breaking study results presented at the BMT Tandem Meetings.
This treatment group showed superior GVHD-free and relapse-free survival at 1 year, lower rates of severe GVHD and chronic GVHD requiring systemic immunosuppression, and improved GVHD-free survival compared with patients treated with tacrolimus and methotrexate.
“The study was developed with the idea of testing new strategies for the prevention of GVHD,” Javier Bolaños Meade, MD, associate professor of oncology and clinical director of the BMT Program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, told HemOnc Today. “The current standard of care (methotrexate and a calcineurin inhibitor) was developed last century and no major advance has occurred since. However, a few single center studies provided data on promising approaches to improve on the standard: the use of bortezomib [Velcade, Millennium/Takeda], maraviroc [Selzentry, Pfizer] and posttransplant cyclophosphamide.
“The idea was to compare, on a randomized phase 2 study, each agent against contemporary controls receiving methotrexate and a calcineurin inhibitor. If any agent was superior, then this could be tested in a phase 3 vs. the standard,” Bolaños Meade added.
In the phase 2 multicenter PROGRESS I trial, researchers randomly assigned patients aged 18 to 75 years with hematologic malignancies eligible for reduced-intensity conditioning allogeneic HSCT 1:1:1 to one of three GVHD prophylaxis regimens:
- tacrolimus, methotrexate and oral maraviroc 300 mg twice per day on days –3 to +30 (n = 92);
- tacrolimus, methotrexate and bortezomib 1.3 mg/m2 on days 1, 4 and 7 (n = 90); or
- tacrolimus and mycophenolate mofetil plus posttransplant cyclophosphamide 50 mg/kg daily on days 3 and 4 (n = 92).
Researchers compared the treatment groups with a nonrandomized prospective contemporaneous tacrolimus plus methotrexate control cohort (n = 224).
All patients received peripheral blood stem cell grafts from 6/6 HLA-matched related or 7-8/8 HLA-matched unrelated donors.
GVHD-free and relapse-free survival — defined as time from transplantation to onset of grade 3 or grade 4 acute GVHD, chronic GVHD requiring systemic immunosuppression, relapse or death — served as the primary endpoint.
Only the tacrolimus and mycophenolate mofetil plus posttransplant cyclophosphamide (Tac/MMF/PTCy) arm showed superior GVHD-free and relapse-free survival compared with the control arm (HR = 0.72; 90% CI, 0.54-0.94).
Researchers observed no differences in incidence of grade 2 through grade 4 acute GVHD between any treatment arm and the control arm.
However, the Tac/MMF/PTCy arm appeared associated with fewer incidences of grade 3 to grade 4 acute GVHD (HR = 0.13; 90% CI, 0.03-0.44) and increased GVHD-free survival (0.63; 90% CI, 0.46-0.85).
Although no differences were observed in overall incidence of chronic GVHD, the Tac/MMF/PTCy arm had lower incidence of chronic GVHD requiring systemic immunosuppression compared with controls (HR = 0.57; 90% CI, 0.36-0.89).
Differences in treatment-related death were not statistically significant between the study arms and the control arm. Researchers did not observe differences in engraftment, relapse/progression and OS.
A phase 3 study to confirm the results is planned, Bolaños Meade said. – by Cassie Homer
Bolaños-Meade J, et al. Abstract LBA1. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.
Disclosures: Bolaños-Meade reports receiving honoraria from Incyte for Data and Safety Monitoring Board participation. Please see the abstract for all other authors’ relevant financial disclosures.