Daratumumab Improves Depth of Response and Progression-free Survival in Transplant-ineligible, High-risk, Newly Diagnosed Multiple Myeloma

Andrzej J. Jakubowiak, Shaji Kumar, Rohan Medhekar, Huiling Pei, Patrick Lefebvre, Shuchita Kaila, Jianming He, Marie Hélène Lafeuille, Annelore Cortoos, Anil Londhe, Panagiotis Mavros, Thomas S. Lin, Saad Z. Usmani

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Patients with high-risk, newly diagnosed multiple myeloma (HR-NDMM) who are ineligible for autologous stem cell transplant (ASCT) have limited first-line treatment options. Recent meta-analyses evaluating the impact of incorporating daratumumab in the backbone regimen on progression-free survival (PFS) have found mixed results in these patients. MATERIALS AND METHODS: A pooled analysis of patient-level data for ASCT-ineligible patients with HR-NDMM [ie, del(17p), t(4;14), t(14;16)] from the MAIA and ALCYONE trials; stratified by study identifier and adjusting for cytogenetic abnormality subtype, baseline performance status, International Staging System stage, myeloma type, and renal impairment; was conducted. Impact of daratumumab on PFS and rates of complete response or better (≥CR), minimal residual disease (MRD)-negative CR, very good partial response or better (≥VGPR), and overall response (ORR) was compared to control. RESULTS: Among 101 patients in the daratumumab and 89 patients in the control cohort, median follow-up was 43.7 months. Daratumumab reduced the risk of progression or death by 41% (adjusted hazard ratio for PFS [95% confidence interval (CI)] = 0.59 [0.41-0.85]) versus control. At 36 months, the estimated proportion of patients who did not progress and were still alive was 41.3% in the daratumumab and 19.9% in the control cohort. Rates of ≥CR (41.6% vs. 22.5%), MRD-negative CR (24.8% vs. 5.6%), ≥VGPR (75.2% vs. 46.1%), and ORR (92.1% vs. 74.2%) were higher for daratumumab versus control. CONCLUSION: These findings demonstrate that incorporation of daratumumab in frontline treatment regimens reduced the risk of progression or death and improved response rates among ASCT-ineligible HR-NDMM patients.

Original languageEnglish (US)
Pages (from-to)e589-e596
JournalThe oncologist
Volume27
Issue number7
DOIs
StatePublished - Jul 5 2022

Keywords

  • cytogenetics
  • daratumumab
  • minimal residual disease
  • multiple myeloma
  • progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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