Cyclophosphamide after transplant reduced GVHD in myeloma patients


Post-transplantation cyclophosphamide may help decrease the rate of nonrelapse mortality and graft-versus-host disease (GVHD) in patients who have undergone allogeneic blood or marrow transplantation, according to new findings published in Biology of Blood and Marrow Transplantation.

Even though it is a potentially curative option for patients with poor-risk hematologic malignancies, allogeneic blood or marrow transplantation (alloBMT) has not been commonly used in multiple myeloma because of its association with high nonrelapse mortality and high relapse rates. However, the use of post-transplantation cyclophosphamide (PTCy) in this study led to low rates of both acute and chronic GVHD, which translated to low rates of nonrelapse mortality and maintenance of long-term remissions in a subset of patients with multiple myeloma treated at Johns Hopkins Hospital, Baltimore.

“The favorable toxicity profile of alloBMT using PTCy in patients with MM offers the potential to further explore the use of post-transplantation strategies to improve disease control,” wrote Nilanjan Ghosh, MD, of the Levine Cancer Institute, Charlotte, N.C., and his colleagues.

The researchers examined outcomes of 39 patients with multiple myeloma who underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors after either myeloablative or nonmyeloablative conditioning.

Patients who underwent myeloablative conditioning received PTCy 50 mg/kg per day (given intravenously on days 3 and 4 after alloBMT) as GVHD prophylaxis, while those who received nonmyeloablative conditioning received PTCy (same dose and schedule) and additional immunosuppression with mycophenolate mofetil 15 mg/kg (orally two to three times daily, up to 1,000 mg/dose on days 4-35 after transplantation).

At a median follow-up of 10.3 years following alloBMT, 23% of the cohort remained alive and without any evidence of disease. The median overall survival was 4.4 years. The 5-year survival probability was 49% (95% confidence interval, 32%-67%) and 10-year survival probability was 43% (95% CI, 29%-62%).

Following transplantation, 10 (26%) patients achieved a complete response, 8 (21%) had a very good partial response, 6 (15%) had a partial response, and 15 (38%) had progressive disease, the investigators reported ( Biol Blood Marrow Transplant. 2017 Nov;23[11]:1903-9 ).

Among the 36 patients with evidence of donor engraftment, the cumulative incidences of grade 2-4 and grade 3 and 4 acute GVHD were 0.41 (95% CI, 0.25-0.57) and 0.08 (95% CI, 0.01-0.16), respectively. For chronic GVHD, the cumulative incidence was 0.13 (95% CI, 0.02-0.23), and the median time to development was 109 days after alloBMT.

The median progression-free survival was 12 months (95% CI, 7.6-40), and the estimated cumulative incidence of relapse was 0.46 (95% CI, 0.3-0.62) at 1 year and 0.56 (95% CI, 0.41-0.72) at 2 years.

In univariate analysis, achievement of a complete response following alloBMT correlated with overall survival. Factors such as the intensity of the alloBMT conditioning regimen, stem cell source, age, and disease response before alloBMT did not appear to impact overall survival.

“Given the low incidence of GVHD and [nonrelapse mortality] in our study, it is possible that post-transplantation maintenance therapies can be used to improve diseases control,” Dr. Ghosh and his associates wrote. “Emerging data suggest that many anticancer agents may be more active after alloBMT than before transplantation.”

The study was funded in part by grants from the National Institutes of Health. The researchers reported having no relevant financial disclosures.