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- Title
Comparative Meta-Analysis of Triplet vs. Quadruplet Induction Regimens in Newly Diagnosed, Treatment Naïve, Multiple Myeloma.
- Authors
Paul, Barry; Anwer, Faiz; Raza, Shahzad; Mammadzadeh, Aytaj; Khasawneh, Bayan; Shatnawi, Sara; McGuirk, Joseph; Ahmed, Nausheen; Mahmoudjafari, Zahra; Mushtaq, Muhammad; Abdallah, Al-Ola; Atrash, Shebli
- Abstract
Simple Summary: Induction regimens using 4-drugs for patients with newly diagnosed multiple myeloma have shown impressive results in multiple trials. However, trials of 4-drug regimens typically use a 3-drug regimen as their comparator, which limits our ability to determine whether the benefit is from the specific combination of drugs or just the addition of more agents. We performed a meta-analysis to compare all trials that compared 4-drug to 3-drug regimens and found that the addition of an anti-CD38 antibody (daratumumab or isatuximab) resulted in improved responses, while 4-drug regimens without an anti-CD38 antibody performed similarly to 3-drug regimens. While the addition of an anti-CD38 antibody led to increased adverse effects, these were predominantly mild and easily managed. These data suggest that an anti-CD38 antibody should be part of all 4-drug induction regimens for newly diagnosed myeloma patients. The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients.
- Subjects
THERAPEUTIC use of antineoplastic agents; MULTIPLE myeloma diagnosis; THERAPEUTIC use of monoclonal antibodies; MULTIPLE myeloma; DRUG toxicity; DRUG side effects; ANTINEOPLASTIC agents; META-analysis; DESCRIPTIVE statistics; PROGRESSION-free survival; CONFIDENCE intervals; INDUCTION chemotherapy; OVERALL survival
- Publication
Cancers, 2024, Vol 16, Issue 17, p2938
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16172938