Clinical Outcomes Associated with Anti-CD38 Retreatment in Relapsed/Refractory Multiple Myeloma: A Review of the Literature

OBJECTIVES: To explore the clinical benefit of anti-(α)CD38-based retreatment in patients with relapsed/refractory multiple myeloma (RRMM).

METHODS: This targeted literature review searched Embase, MEDLINE, and MEDLINE In-Process (database inception–July 10, 2023), 5 pre-selected conference proceedings (2016–August 21, 2023), and clinicaltrials.gov for records published in English. Publications were screened for eligibility using PICOS criteria: studies (observational/interventional) reporting clinical outcomes (overall survival [OS], progression-free survival [PFS], overall response rate [ORR]) of αCD38-based retreatment in adults with RRMM. Data were extracted from eligible publications by one reviewer, then validated by a second reviewer.

RESULTS: Overall, 32/2457 screened publications were included, comprising 23 studies: 6 clinical trials and 17 real-world evidence studies (RWE). Population size, median follow-up, and patient clinical characteristics varied considerably across studies.

Across 7 RWE, median (95% CI) OS (months) after αCD38-based retreatment varied from 8.4 (6.7–10.0) to 19 (13.5–24.5). Across 9 RWE, median (95% CI) PFS (months) was 1.5 (NR)–8.4 (2.8–NE); PFS was shorter in studies with >95% αCD38-refractory patients (3.3 [0–6.93]­–5 [1.5–8.4]). In 1 RWE that compared different αCD38-retreatment subgroups, median (95% CI) PFS (months) was longer in those previously αCD38-exposed but not refractory than in αCD38-refractory patients (8.4 [2.8–NR] versus 3.0 [2.4–4.8]).

Across trials (n=6), ORR varied between 0% (n=3) and 75% (n=1; talquetamab-combination therapy). Across RWE (n=13), ORR was 25–90% (90% among 10 penta-refractory patients, most with stem cell transplant in a previous line; 60% of RWE reported ORR <50%). ORR was generally lower in RWE with more prior lines of therapy and those with higher proportions of αCD38-refractory patients.

CONCLUSIONS: This review demonstrates a paucity of high-quality evidence evaluating αCD38 retreatment. The limited data available indicates that αCD38-retreated patients experience suboptimal outcomes indicating high unmet needs for alternative treatments.

FUNDING: GSK (221354)