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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell
Satoshi Yamasaki1, Michitoshi Hashiguchi1, Nao Yoshida-Sakai1
1Department of Hematology, St. Mary's Hospital, Kurume 830-8543, Japan.
Background:
The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging.
Methods:
We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023.
Results:
Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (i.e., those previously treated with daratumumab and receiving isatuximab plus pomalidomide and low-dose dexamethasone because of disease progression during treatment with daratumumab [n = 6], daratumumab plus pomalidomide and low-dose dexamethasone [n = 9], or isatuximab plus pomalidomide and low-dose dexamethasone without daratumumab-exposure [n = 14]) than in the anti-CD38 mAb-naïve group (no exposure to daratumumab or isatuximab [n = 49]) (p < 0.001). To address potential confounder factors associated with use or nonuse of anti-CD38 mAbs, we performed propensity score matching (PSM) using age, sex, performance status, and Geriatric 8 and Instrumental Activities of Daily Living scores. PSM identified 14 subjects from the anti-CD38 mAb-exposed group with baseline characteristics similar to those of 14 subjects from the anti-CD38 mAb-naïve group. After PSM, the adjusted OS was significantly longer in the anti-CD38 mAb-exposed group than in the anti-CD38 mAb-naïve group (p < 0.001).
Conclusion:
These findings provide insights into the optimal use of anti-CD38 mAbs in patients with RRMM who are transplant-ineligible and aged ≥65 years and on candidates who are appropriate for novel approaches, such as chimeric antigen receptor T-cell or bispecific T-cell engager therapy.
Insights
Anti-CD38 monoclonal antibodies (mAbs) significantly improve survival in older transplant-ineligible patients with relapsed or refractory multiple myeloma (RRMM). This study confirms their benefit in this challenging patient population.
Area of Science:
- Hematology
- Oncology
- Clinical Medicine
Background:
- Relapsed or refractory multiple myeloma (RRMM) treatment has improved with agents like anti-CD38 monoclonal antibodies (mAbs).
- Older, transplant-ineligible RRMM patients present unique treatment challenges.
- Optimizing anti-CD38 mAb use in this demographic is crucial.
Purpose of the Study:
- To evaluate the overall survival (OS) of transplant-ineligible patients aged ≥ 65 years with RRMM.
- To assess the impact of prior anti-CD38 mAb exposure on OS in this population.
- To provide insights into novel therapeutic approaches for elderly RRMM patients.
Main Methods:
- Retrospective analysis of 78 transplant-ineligible RRMM patients (≥ 65 years).
- Comparison of OS between anti-CD38 mAb-exposed and anti-CD38 mAb-naïve groups.
- Propensity score matching (PSM) to control for confounding factors (age, sex, performance status, geriatric assessments).
Main Results:
- Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (p < 0.001).
- After PSM, adjusted OS remained significantly longer in the anti-CD38 mAb-exposed group (p < 0.001).
- This suggests a survival benefit associated with anti-CD38 mAb use in this cohort.
Conclusions:
- Anti-CD38 mAbs demonstrate a significant survival benefit in transplant-ineligible RRMM patients aged ≥ 65 years.
- Findings support the use of anti-CD38 mAbs in this challenging patient group.
- This research informs the selection of appropriate novel therapies, including CAR T-cell and bispecific T-cell engager therapies.
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