Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Standard of Care in Latin America for Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Propensity Score Matching Analysis.

Abstract

INTRODUCTION:

The phase 3 ALCYONE study demonstrated significantly longer progression-free and overall survival (PFS/OS) and higher overall response rates (ORR) with daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In Latin America, bortezomib- or thalidomide-based regimens remain standard of care (SoC) for this population. No head-to-head trials have compared D-VMP with SoC regimens used in Latin America.

METHODS:

Propensity score matching (PSM) was used to control for baseline differences between patient populations and compare outcomes for D-VMP versus SoC regimens used in Latin America. Data for the D-VMP cohort were from the D-VMP arm of the ALCYONE trial (n = 350). Data for the SoC cohort were from the retrospective, observational Hemato-Oncology Latin America (HOLA) study, which included patients with NDMM who did not receive a transplant (n = 729). Propensity scores were estimated using logistic regression. Exact, optimal, and nearest-neighbor PSM were applied to pick the best-performing method. Doubly robust estimation was the base case, since some baseline imbalances persisted.

RESULTS:

All 350 patients from the D-VMP arm of ALCYONE were included in OS/PFS analyses and 338 in ORR analysis; 478 and 324 patients, respectively, from HOLA were included in these analyses. Naïve comparison revealed important differences in baseline characteristics (age, chronic kidney disease, hypercalcemia, and International Staging System [ISS] stage). After nearest-neighbor matching, baseline characteristics, except ISS stage, were well balanced; comparisons favored D-VMP over SoC for OS (hazard ratio = 0.41; 95% confidence interval [CI] 0.25-0.66; P = 0.002) and PFS (hazard ratio = 0.48; 95% CI 0.35-0.67; P < 0.001). After exact matching, imbalances remained in age and ISS stage; comparisons favored D-VMP over SoC for ORR (odds ratio = 5.44; 95% CI 2.65-11.82; P < 0.001).

CONCLUSION:

In transplant-ineligible patients with NDMM, D-VMP showed superior effectiveness versus bortezomib- and thalidomide-based regimens, supporting adoption of daratumumab-containing regimens in Latin America.

• Authors: Vania Hungria, Deborah M Martínez-Baños, María-Victoria Mateos, Meletios A Dimopoulos, Michele Cavo, Bart Heeg, Andrea Garcia, Annette Lam, Gerardo Machnicki, Jianming He, Mariana Fernandez
• Journal: Advances in therapy (Adv Ther) Vol. 37 Issue 12 Pg. 4996-5009 (12 2020) ISSN: 1865-8652 [Electronic] United States
• PMID: 33067698 (Publication Type: Clinical Trial, Phase III, Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• daratumumab
• Bortezomib
• Melphalan
• Prednisone

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bortezomib (therapeutic use)
• Female
• Humans
• Latin America
• Male
• Melphalan (therapeutic use)
• Middle Aged
• Multiple Myeloma (drug therapy)
• Prednisone (analogs & derivatives, therapeutic use)
• Progression-Free Survival
• Propensity Score
• Retrospective Studies
• Standard of Care