Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma.

Abstract

BACKGROUND:

Combination therapy regimens containing a proteasome inhibitor, an immunomodulatory drug, and a steroid are an established standard of care for patients with newly diagnosed multiple myeloma (NDMM) regardless of transplant eligibility. Triplet regimens that include lenalidomide/dexamethasone combined with daratumumab or carfilzomib are highly active in multiple myeloma, including NDMM. The aim of this open-label, phase 1b study was to evaluate daratumumab in combination with carfilzomib, lenalidomide, and dexamethasone (D-KRd) in patients with NDMM.

PATIENTS AND METHODS:

Patients (n = 22), regardless of transplant eligibility, received treatment with D-KRd for up to thirteen 28-day cycles or until autologous stem cell transplant. The first daratumumab dose was administered as a split infusion (8 mg/kg on days 1 and 2 of cycle 1). The primary end point was safety and tolerability.

RESULTS:

A total of 10 patients discontinued treatment, most frequently because of elective autologous stem cell transplant (n = 8). The most common treatment-emergent adverse events (any grade; grade 3/4) were diarrhea (68%; 18%), lymphopenia (64%; 59%), cough (59%; 5%), and upper respiratory tract infection (55%; 0%). Stem cell collection was successful in most patients (91%). Daratumumab infusion-related reactions occurred in 9 (41%) patients, primarily during the first infusion, and were mild in severity (no grade 3/4 events). The best overall response rate was 95%, including 86% with a very good partial response or better and 67% with a complete response or better.

CONCLUSION:

D-KRd was well tolerated, and encouraging efficacy results support further investigation of daratumumab-based quadruplet therapies for NDMM.

• Authors: Andrzej Jakubowiak, Saad Z Usmani, Amrita Krishnan, Sagar Lonial, Raymond L Comenzo, Jianping Wang, Carla de Boer, William Deraedt, Brendan M Weiss, Jordan M Schecter, Ajai Chari
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 21 Issue 10 Pg. 701-710 (10 2021) ISSN: 2152-2669 [Electronic] United States
• PMID: 34274290 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Antibodies, Monoclonal
• Oligopeptides
• daratumumab
• carfilzomib
• Dexamethasone
• Lenalidomide

Topics

• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Dexamethasone (pharmacology, therapeutic use)
• Female
• Humans
• Lenalidomide (pharmacology, therapeutic use)
• Male
• Multiple Myeloma (drug therapy)
• Oligopeptides (pharmacology, therapeutic use)