A new analysis shows that a donor stem cell transplant following treatment with an immune checkpoint inhibitor is generally safe and produces good outcomes for patients with Hodgkin lymphoma, easing concerns that these patients are at heightened risk for severe immune-related complications.
The study, to be presented today at the 61st American Society of Hematology (ASH) Annual Meeting by Reid Merryman, MD, attending physician in the Lymphoma Program at Dana-Farber Cancer Institute, also found that post-transplant treatment with the drug cyclophosphamide may lead to improved results for many patients.
The study focused on the safety of donor stem cell transplantation in patients with classic Hodgkin lymphoma who were previously treated with a PD-1 inhibitor, a drug that unleashes an immune system attack on tumor cells. While PD-1 inhibitors produce responses in about 70% of these patients, many develop resistance to the drugs within a few years. For that reason, patients are often recommended for a donor stem cell transplant, which can cure the disease.
Because PD-1 inhibitors let loose an immune system attack, there had been concerns of immune-related problems such as acute graft-versus-host disease (GVHD), in which immune cells from transplanted tissue attack patients' normal, healthy tissue. Several previous studies, including one by Dana-Farber investigators, seemed to justify those concerns, but the studies enrolled relatively small numbers of patients and had a short follow-up period.
The new study pooled data from 150 patients at 26 transplant centers across the U.S. and Europe who had undergone a donor cell transplant after a median of 10 doses of a PD-1 or PD-L1 inhibitor (PD-L1 is an immune checkpoint protein on some tumor cells). Fifty-nine percent of the patients were treated with cyclophosphamide to lower their risk of GVHD.
At a median of two years after their transplant, 79% of the patients were alive and 65% had no evidence of lymphoma. Twenty-one percent had relapsed. Six months post-transplant, 39% of patients had developed acute GVHD, including 8% who had severe, life-threatening acute GVHD – a rate that was lower than in previous, smaller studies, Merryman noted. Investigators found that patients treated with cyclophosphamide post-transplant generally fared better and had lower rates of chronic GVHD and relapse.
Our results indicate that treatment with a PD-1 or PD-L1 inhibitor in advance of a donor stem cell transplant is safe and can provide good outcomes for these patients, and inclusion of cyclophosphamide treatment as part of GVHD prevention may provide an additional benefit."
Reid Merryman, MD, attending physician in the Lymphoma Program at Dana-Farber Cancer Institute
Researchers discover how mutations disrupt protein splicing and cause disease