Highlights
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Ipilimumab in combination with nivolumab can be safely used as a consolidation strategy after autologous stem cell transplantation for high-risk hematologic malignancies.
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Combined checkpoint inhibition has the potential to skew the recovering immune milieu post-ASCT towards an effector, rather than a regulatory phenotype.
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Combined checkpoint inhibition may be a strategy to improve outcomes following ASCT, particularly in patients with diffuse large B-cell lymphomas.
Abstract
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 transplant-naïve 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.
Key Points: Combined immune checkpoint inhibitor therapy is safe as a consolidation strategy
following ASCT for high-risk hematologic malignancies and may have clinical efficacy
that warrants further evaluation
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Article Info
Publication History
Accepted:
December 27,
2020
Received:
September 29,
2020
Publication stage
In Press Accepted ManuscriptIdentification
Copyright
© 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.
