The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy 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.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.


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.