Abstract
<h3>Background</h3> The phase 3 IKEMA trial evaluated isatuximab plus carfilzomib and dexamethasone (IsaKd) for relapsed multiple myeloma after 1–3 therapy lines. As no head-to-head comparison exists, we compared IsaKd vs daratumumab plus lenalidomide and dexamethasone (DaraRd) via matching-adjusted indirect comparison (MAIC). <h3>Methods</h3> Individual patient data from IKEMA (IsaKd arm, NCT03275285) were matched to aggregate data from the phase 3 POLLUX trial (DaraRd arm) by a two-step process. First, POLLUX inclusion criteria (creatinine clearance >30 mL/min; hemoglobin >7.5 g/dL; platelet count >75×10<sup>9</sup>/L; non-lenalidomide-refractory) were applied to the IKEMA IsaKd arm. Second, data for remaining IsaKd patients were re-weighted by their odds of enrolment in POLLUX so that key baseline characteristics were matched with the DaraRd arm. Matched-on characteristics were age (≤64; 65–74; ≥75), Eastern Cooperative Oncology Group performance status (0; 1–2), number of prior therapy lines (1; ≥2), disease stage at entry (I or II; III), cytogenetic risk (standard; high; unknown), prior treatment (proteasome inhibitor [PI]; lenalidomide; immunomodulatory drug [IMiD]), and refractory status (PI-refractory only; IMiD-refractory only). Matching-adjusted progression-free survival (PFS), overall survival (OS) and depth of response rate were compared for IsaKd vs DaraRd. Hazard ratios (HR) and 95% confidence intervals (CI) for PFS and OS were generated by Cox proportional hazard models. Odds ratios (OR) for ≥Very Good Partial Response rate (VGPR) were calculated as the proportion of patients with complete response (CR), stringent CR, and VGPR as best overall response; 95% CI and p values were calculated by Wald tests. <h3>Results</h3> After applying POLLUX inclusion criteria (before matching), significant (p3 prior therapy lines (0 vs 4.9%), high cytogenetic risk (24.1% vs 12.2%), and who were IMiD-refractory (9.8% vs 3.5%). After matching, there were no significant differences for IsaKd vs DaraRd except for patients with >3 prior lines (0% vs 4.9%). PFS was significantly better with IsaKd vs DaraRd (HR [95% CI]: 0.46 [0.24–0.86]; p=0.0155). There was a numeric, non-significant, improvement favoring IsaKd for OS (HR [95% CI]: 0.47 [0.20–1.09]; p=0.0798) and VGPR (OR [95% CI]: 1.53 [0.89–2.64]; p=0.1252). <h3>Conclusion</h3> Lenalidomide-based regimens are frequently used in non-lenalidomide-refractory patients until progression. After adjusting for differences in inclusion criteria and baseline characteristics, this MAIC showed significantly better PFS with IsaKd vs DaraRd, the current gold standard in early relapse. In addition, a non-significant numeric trend in favor of IsaKd was observed for OS and VGPR rate. These data suggest that switching to IsaKd vs DaraRd in early relapse in non-lenalidomide-refractory patients may provide superior outcomes. This study was funded by Sanofi.
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