Safety and efficacy of consolidation therapy with ipilimumab plus nivolumab after autologous stem cell transplantation

Background: Autologous hematopoietic stem cell transplantation (ASCT) is a standard-of-care treatment for many hematological malignancies. Progression of disease after ASCT is the primary cause of treatment failure. Objective: In this Phase Ib trial, we studied the safety and clinical effect of combined checkpoint inhibition with ipilimumab and nivolumab as a consolidation strategy after ASCT for patients with high-risk diffuse large B-cell Lymphoma (DLBCL), mature T-cell lymphoma (TCL) and multiple myeloma (MM). Study Design: Starting 14-28 days after ASCT, patients received ipilimumab (1 mg/kg, intravenous, on day 1 of weeks 1, 4, 7, 10, 16, 22) and nivolumab (3 mg/kg, intravenous, on day 1 of weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26). Results: Patients received a median of five doses of ipilimumab and eight doses of nivolumab. Thirty-five patients were included in the intent-to-treat population. Ninety-four percent of patients experienced immune-related adverse events (irAEs) of any grade. Ninety-seven percent of irAEs resolved spontaneously or by holding study drugs and instituting high-dose corticosteroid therapy. Progression-free and overall survival at 18 months post-ASCT for each disease cohort were, respectively: primary refractory DLBCL, 85.7% and 100%; relapsed DLBCL, 28.6% and 57.1%; frontline TCL: Not Evaluable and 80%; relapsed TCL, 25% and 75%; high-risk transplantnaïve MM, 57.1% and 87% and MM relapsed within 3 years of first ASCT, 40% and 100%. Conclusion: We conclude that combined checkpoint inhibition appears tolerable as a consolidation strategy after ASCT and in addition to the potential clinical efficacy observed in some subsets of disease, T cell receptor repertoire, Tregulatory phenotype and gut microbiota profiles provide a biologic rationale warranting further study of this approach.