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

Oncologist. 2022 Jul 5;27(7):e589-e596. doi: 10.1093/oncolo/oyac067.


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.

Keywords: cytogenetics; daratumumab; minimal residual disease; multiple myeloma; progression-free survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bortezomib / therapeutic use
  • Humans
  • Multiple Myeloma*
  • Progression-Free Survival
  • Treatment Outcome


  • Antibodies, Monoclonal
  • daratumumab
  • Bortezomib