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.

Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Chen YB, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol 2013 Oct 14 [Epub ahead of print].

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