Abstract
Pidilizumab is active and safe in DLBCL after autologous hematopoietic stem cell transplant.
Major finding: Pidilizumab is active and safe in DLBCL after autologous hematopoietic stem cell transplant.
Clinical relevance: PD-1 blockade may eliminate residual disease and increase survival after transplant.
Impact: Inhibition of immune check-points may be therapeutically effective in hematologic malignancies.
Ligand stimulation of the programmed cell death 1 (PD-1) receptor on activated immune cells inhibits antitumor T-cell immune responses, and targeted blockade of PD-1 has shown promising results in some solid tumors. In patients with hematologic malignancies such as diffuse large B-cell lymphoma (DLBCL), autologous hematopoietic stem cell transplant (AHSCT) results in remodeling of the immune system in the context of minimal residual disease, suggesting that PD-1 inhibition may be particularly effective in this setting. To test this hypothesis, Armand and colleagues evaluated the safety and activity of pidilizumab, an anti-PD1 antibody that has shown antitumor activity in preclinical models and phase I trials, in 66 patients with DLBCL who received AHSCT. Pidilizumab was well tolerated and did not induce autoimmune toxicity or treatment-related mortality. The proportion of patients who experienced a 16-month interval of progression-free survival (PFS) was 0.72, and the proportion of patients who experienced a 16-month interval of overall survival was 0.85. Among 35 patients with measurable disease after AHSCT, pidilizumab resulted in complete remission in 34%, partial remission in 17%, and stable disease in 11% of patients, corresponding to an overall response rate of 51% and a median time to response of 30 weeks. Analysis of circulating leukocyte subsets following pidilizumab treatment identified a rapid increase in the number of PD-L1–expressing CD4+CD25+ activated helper T cells, consistent with suppression of PD-1–mediated inhibition of T-cell survival. In addition, pidilizumab induced elevated numbers of circulating CD8+ and CD4+ memory T cells and increased expression of the interleukin-7α receptor, CD127, which promotes T-cell maturation and survival. These findings suggest that PD-1 blockade improves PFS in patients with DLBCL after AHSCT but that phase III trials are needed to validate this therapeutic approach in DLBCL and other hematologic malignancies.
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