P-057: Comparative Efficacy of Cilta-Cel vs Approved Comparator Treatments for Patients With Relapsed/Refractory Multiple Myeloma With 1–3 Prior Lines of Therapy: A Network Meta-Analysis

Introduction: In the phase 3 CARTITUDE-4 trial, ciltacabtagene autoleucel (cilta-cel) prolonged progression-free survival (PFS) vs standard of care (SOC) (HR [weighted], 0.26; P< 0.0001; HR [unweighted], 0.40; P< 0.0001) in patients with lenalidomide (len)-refractory multiple myeloma (MM) and 1–3 prior lines of therapy (LOT), including a proteasome inhibitor and an immunomodulatory drug. We report the results of a network meta-analysis (NMA) that compared cilta-cel efficacy vs relevant SOC comparators based on target trial populations, including len-refractory patients who received 1–3 prior LOT.

Methods: Comparators of interest were identified a priori based on approved and commonly used SOC regimens in the United States, United Kingdom, Spain, France, Germany, Italy, Canada, and the Netherlands. A systematic literature review was conducted, and a total of 22 trials were assessed for feasibility by comparing the study design and degree of overlap with the CARTITUDE-4 population. The comparator arm in CARTITUDE-4 is SOC treatment with physician’s choice of daratumumab, pomalidomide, dexamethasone (DPd) or pomalidomide, bortezomib, dexamethasone (PVd). DPd was the most common treatment in the SOC arm of CARTITUDE-4 (87% of patients), and PFS results for the DPd cohort were similar to the intent-to-treat (ITT) population; therefore, the assumption that the SOC arm was comparable to the DPd arm in APOLLO was made to form a network of trials. This network was centralized around pomalidomide in combination with dexamethasone (Pd) and included the CARTITUDE-4 (cilta-cel), APOLLO (DPd + Pd), ELOQUENT-3 (elotuzumab, pomalidomide, dexamethasone [EloPd]), ICARIA-MM (isatuximab, pomalidomide, dexamethasone [IsaPd]), and OCEAN (melflufen, dexamethasone [Md]) trials. NMAs were performed using fixed-effects Bayesian models to assess the outcome of PFS in the ITT and subgroups, including len-refractory and patients with 2–3 prior LOT.

Results: The NMA showed cilta-cel had a statistically significant PFS benefit vs all comparators of interest and across all populations analyzed. Results favored cilta-cel across all comparator regimens in the full ITT populations (HR range, 0.25–0.49), the len-refractory subgroup (HR range, 0.27–0.45 [EloPd was excluded because data for this subgroup were not reported in ELOQUENT-3]), and the 2–3 prior LOT subgroup (HR range, 0.26–0.47).

Conclusions: These comparisons provide valuable information to contextualize the efficacy of cilta-cel in which treatment for these patients may be different from DPd or PVd. The NMA showed that cilta-cel had a statistically significant PFS benefit vs all feasible comparators (Pd, EloPd, IsaPd, Md). Results of the NMA should be supplemented with matching-adjusted indirect comparisons given key differences across the included trials with regard to effect modifiers (eg, number of prior LOT, ISS stage, cytogenetic risk).