The following article features coverage from the 61st American Society of Hematology Annual Meeting and Exposition. Click here to read more of Hematology Advisor’s conference coverage.

According to results of a study reported in a plenary session at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) administration of cyclophosphamide plus cyclosporine was associated with a significantly lower incidence of graft-versus-host disease (GVHD) compared with conventional immunosuppression.

GVHD is a major cause of morbidity and mortality following allo-HSCT in patients with hematologic cancers. Although studies evaluating high-dose cyclophosphamide with or without cyclosporine A in the posttransplant setting have shown low risks of GVHD, there is a dearth of randomized evidence comparing this approach with conventional posttransplant immunosuppression.

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In this randomized, multicenter phase 3 clinical trial (HOVON-96), 160 adult patients with high-risk hematological malignancies and a related or closely matched unrelated donor were randomly assigned in a 2:1 ratio to receive GVHD-related prophylactic therapy with high-dose cyclophosphamide (50 mg/kg of day +3 and +4 followed by cyclosporine A from day +5 until day +70) or cyclosporine A (day -3 to +180) plus mucophenolic acid (day 0 to +84) following allo-HSCT with either a matched related donor or a closely matched unrelated donor.

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Of the 151 patients proceeding to allo-HSCT, 97% received reduced-intensity conditioning therapy, approximately 30% had a matched sibling donor, and 97% received blood-derived transplants.

At a median follow-up of 38.7 months, key study findings included a significantly lower incidence of acute GVHD (grade 2-4) in patients receiving cyclophosphamide-based treatment compared with conventional immunosuppression at 6 months (48% vs 32%; P =.014). These results were also reflected in the 2-year cumulative incidence of chronic GVHD, which was 50% for those receiving conventional immunosuppression and 19% for those receiving cyclophosphamide (P =.001).

No significant differences were seen in the cumulative incidence of relapse/progression or nonrelapse mortality, and progression-free survival and overall survival of patients in the 2 study arms were similar.

However, rates of a composite study end point, GVHD-free, relapse-free survival, reflecting survival without grade 3/4 acute GVHD, chronic GVHD requiring systemic immunosuppression, disease relapse, or death, were significantly higher at 12 months for patients receiving cyclophosphamide-based therapy (45%) in the posttransplant setting compared with conventional immunosuppression (22%; P =.001). Notably, these findings were independent of whether the donor was related or matched/related.

Regarding safety, the rates of grade 3/4 infections (41% vs 21%) and grade 3/4 neutropenic fever (25% vs 15%) were higher in the cyclophosphamide-based arm compared with those receiving conventional immunosuppression.

In her concluding remarks, the presenting author Dr Annoek Broers, the Erasmus MC Cancer Institute, Rotterdam, Netherlands, commented that “application of high-dose posttransplant cyclophosphamide combined with a short course of cyclosporine A results in a significant reduction in grade 2 to 4 acute and chronic GVHD.” She further noted that “high-dose cyclophosphamide does improve significantly GVHD-free, relapse-free survival as compared to conventional immunosuppression, thereby reflecting its long-term benefit and positive impact on the quality of life after allogeneic HSCT.”

Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.


De Jong, CN, Meijer E, Bakunina K, et al.  Post-transplantation cyclophosphamide after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON-96 trial in recipients of matched related and unrelated donors. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 1.

This article originally appeared on Cancer Therapy Advisor