Allogeneic HSCT After PD-1 Blockade Appears Feasible in R/R Lymphoma

Allogeneic hematopoietic stem cell transplantation (HSCT) following treatment with an anti-PD-1 monoclonal antibody appears feasible in patients with relapsed/refractory lymphoma but may be associated with an increased risk for developing early immune toxicity, according to a study published in Blood.¹

Studies are increasingly evaluating the use of PD-1 inhibitors in patients with advanced lymphoma. After treatment, many of those patients are likely to be eligible to undergo allogeneic HSCT, though the efficacy and safety of HSCT after prior PD-1 blockade are unclear.

To determine the impact of prior PD-1 blockade on the safety and efficacy of allogeneic HSCT among patients with advanced lymphoma, researchers conducted an international retrospective analysis of 39 patients with lymphoma who had received prior therapy with an anti-PD-1 monoclonal antibody. Median time before HSCT was 62 days.

Median follow-up was 12 months; the 1-year overall and progression-free survival rates were 89% (95% CI, 74-96) and 76% (95% CI, 56-87), respectively. The 1-year cumulative incidence of non-relapse mortality was 11% (95% CI, 3-23); 14% (95% CI, 4-29) of patients relapsed.

During follow-up, 44% and 23% of patients experienced grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (GVHD), respectively, while the 1-year cumulative incidence of chronic GVHD was 41%.

Seven patients developed a non-infectious febrile syndrome shortly after HSCT, requiring prolonged courses of steroids. Four patients died as a result of treatment.

In a subset of 17 patients, investigators analyzed circulating lymphocyte levels. They found that, in contrast with controls, patients previously treated with a PD-1 inhibitor had significantly decreased PD-1+ T cells and reduced ratios of T regulatory cells to conventional CD4 and CD8 cells.

The findings suggest that allogeneic HSCT after treatment with a PD-1 inhibitor is feasible, but prior PD-1 blockade may trigger long-lasting immune alterations resulting in an increased risk of early immune toxicity.

Reference

1. Merryman RW, Kim HT, Zinzani PL, et al. Safety and efficacy of allogeneic hematopoietic stem cell transplant After PD-1 blockade in relapsed/refractory lymphoma. Blood. 2017 Jan 10. doi: 10.1182/blood-2016-09-738385 [Epub ahead of print]