Daratumumab With Cetrelimab, an Anti-PD-1 Monoclonal Antibody, in Relapsed/Refractory Multiple Myeloma.

Abstract

BACKGROUND:

Daratumumab is approved for relapsed or refractory multiple myeloma (RRMM) as monotherapy or in combination regimens. We evaluated daratumumab plus cetrelimab, a programmed death receptor-1 inhibitor, in RRMM.

PATIENTS AND METHODS:

This open-label, multiphase study enrolled adults with RRMM with ≥ 3 prior lines of therapy. Part 1 was a safety run-in phase examining dose-limiting toxicities of daratumumab (16 mg/kg intravenously weekly for cycles 1-2, biweekly for cycles 3-6, and monthly thereafter) plus cetrelimab (240 mg intravenously biweekly, all cycles). In Parts 2 and 3, patients were to be randomized to daratumumab with or without cetrelimab (same schedule as Part 1). Endpoints included safety, overall response rate, pharmacokinetics, and biomarker analyses.

RESULTS:

Nine patients received daratumumab plus cetrelimab in the safety run-in, and 1 received daratumumab in Part 2 before administrative study termination following a data monitoring committee's global recommendation to stop any trial including daratumumab combined with inhibitors of programmed death receptor-1 or its ligand (programmed death-ligand 1). The median follow-up times were 6.7 months (safety run-in) and 0.3 months (Part 2). No dose-limiting toxicities occurred. All 10 patients had ≥ 1 treatment-emergent adverse event; 7 patients had grade 3 to 4 treatment-emergent adverse events, and none led to treatment discontinuation or death. In the safety run-in, 7 (77.7%) patients had ≥ 1 infusion-related reaction (most grade 1-2), and 1 had a grade 2 immune-mediated reaction. Among safety run-in patients, the overall response rate was 44.4%.

CONCLUSIONS:

No new safety concerns were identified for daratumumab plus cetrelimab in RRMM. The short study duration and small population limit complete analysis of this combination.

• Authors: Yael C Cohen, Albert Oriol, Ka Lung Wu, Noa Lavi, Philip Vlummens, Carolyn Jackson, Wendy Garvin, Robin Carson, Wendy Crist, Jiayu Fu, Huaibao Feng, Hong Xie, Jordan Schecter, Jesús San-Miguel, Sagar Lonial
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 21 Issue 1 Pg. 46-54.e4 (01 2021) ISSN: 2152-2669 [Electronic] United States
• PMID: 33485428 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• daratumumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, mortality)
• Neoplasm Recurrence, Local (drug therapy)
• Survival Analysis