Post-transplant cyclophosphamide (PTCy) plus tacrolimus and mycophenolate mofetil (MMF) should be standard graft-vs-host disease (GVHD) prophylaxis in adults who receive a well-matched peripheral blood stem cell transplant (PBSCT) after reduced intensity conditioning (RIC), according to researchers.
In a phase 3 trial, PTCy plus tacrolimus and MMF reduced the risk of severe acute and chronic GVHD when compared with tacrolimus and methotrexate. Patients who received PTCy plus tacrolimus and MMF also had longer GVHD-free, relapse-free survival (GRFS).
These results were presented at the 2022 ASH Annual Meeting by Shernan G. Holtan, MD, of the University of Minnesota in Minneapolis.
The phase 3 study (ClinicalTrials.gov Identifier: NCT03959241) enrolled 431 patients with leukemia, lymphoma, or myelodysplastic syndrome who were undergoing allogeneic PBSCT. The patients were randomly assigned to receive GVHD prophylaxis with PTCy plus tacrolimus and MMF (n=214) or standard tacrolimus plus methotrexate (n=217).
All patients received RIC. They then received 6/6 matched related donor grafts (28.0% in the PTCy arm and 31.3% in the control arm), 7/8 matched unrelated donor grafts (3.3% and 3.7%, respectively), or 8/8 matched unrelated donor grafts (68.7% and 65.0%, respectively).
The primary endpoint was 1-year GRFS. The 1-year GRFS rate was significantly higher in the PTCy group than in the control group — 52.7% and 34.9%, respectively (hazard ratio [HR], 0.641; P <.001).
The improvement in GRFS was driven primarily by a reduction in severe acute and chronic GVHD. The cumulative incidence of grade 3-4 acute GVHD at day 100 was 6.3% in the PTCy group and 14.7% in the control group (P =.001). The rate of chronic GVHD that required intensive steroid treatment at 1 year was 12.5% and 25%, respectively (P =.001).
The 1-year rate of GVHD-free survival was higher in the PTCy group than in the control group — 61.9% and 44.9%, respectively (P =.0004).
The rate of relapse or progression at 1 year was similar between the groups, at 20.8% in the PTCy group and 20.2% in the control group (P =.906).
The 1-year overall survival rate was 77.0% in the PTCy group and 72.2% in the control group (P =.252). The rate of transplant-related mortality at 1 year was 12.3% and 17.2%, respectively (P =.167).
The cumulative incidence of grade 2-3 infections at 1 year was higher in the PTCy group than in the control group — 40.0% and 30.4%, respectively (P =.018). Most infections occurred within the first month, Dr Holtan noted.
Fewer patients in the PTCy group than in the control group achieved lymphocyte recovery at 1 year — 53.8% and 63.2%, respectively (P <.001).
However, rates of graft failure and chimerism were similar between the groups. The rate of full chimerism at 100 days was 68.6% in the PTCy group and 67.8% in the control group (P =.198). The rates of secondary graft failure were 2.9% and 0.9%, respectively (P =.172).
Deaths due to recurrent or persistent malignancy occurred in 39.6% of patients in the PTCy group and 42.9% of those in the control group. Deaths due to acute GVHD were more common in the control group (14.3% vs 4.2%), but deaths due to organ failure were more common in the PTCy group (22.9% vs 10.7%).
“Based upon these results, we believe that post-transplant cyclophosphamide, tacrolimus, and MMF should be the standard GVHD prophylaxis in well-matched, adult reduced-intensity transplantation,” Dr Holtan concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Holtan SG, Hamadani M, Wu J, et al. Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil as the new standard for graft-versus-host disease (GVHD) prophylaxis in reduced intensity conditioning: Results from phase III BMT CTN 1703. Presented at ASH 2022. December 10-13, 2022. Abstract LBA-4.
This article originally appeared on Cancer Therapy Advisor