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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)701-710
Number of pages10
JournalClinical Lymphoma, Myeloma and Leukemia
Volume21
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • Efficacy
  • Quadruplet regimen
  • Safety

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