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Objectives: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi‐centre, Phase 1, single‐agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)‐modified anti‐CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc‐gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM. Methods: This study comprised two parts: Part‐A (dose‐escalation involving anti‐CD38 mAb pre‐treated and naïve patients) and Part‐B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D). Results: Thirty‐seven heavily pre‐treated patients were treated in Part A. Part‐B (dose‐expansion) was not studied. Seven dose‐limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5–7·5 mg/kg. Most common treatment‐emergent adverse events were infusion‐related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti‐CD38 mAb naïve and 4% in anti‐CD38 pre‐treated patients, with a median progression‐free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively. Conclusions: The efficacy of SAR442085 was promising in anti‐CD38 mAb naïve patients but did not extend to the larger cohort of anti‐CD38 mAb pre‐treated patients. This observation, along with transient high‐grade thrombocytopenia, could potentially limit its clinical use. [ABSTRACT FROM AUTHOR]

Objectives Achieving complete response ( CR) has been linked to improved progression-free ( PFS) and overall ( OS) survival in myeloma. A meta-analysis was conducted to investigate whether this holds true in the era of novel agents (bortezomib, lenalidomide, thalidomide). Methods A total of 24 studies in newly diagnosed patients undergoing autologous stem cell transplantation ( ASCT) that reported associations between responses and long-term outcomes ( PFS/ OS rates post- ASCT by response, or hazard ratios with 95% confidence intervals from Cox models) were identified and analyzed. Results Achievement of CR vs. < CR post- ASCT reduced risk of progression/death by 38% [risk ratio ( RR): 0.62, P < 0.0001]; risk of death was 41% lower ( RR: 0.59, P < 0.0001). Subgroup meta-analyses showed significant PFS risk reduction with CR post- ASCT with novel ( RR: 0.32, P < 0.006) and non-novel ( RR: 0.72, P < 0.0001) agents, and corresponding OS risk reduction with novel ( RR: 0.33, P = 0.0013) and non-novel ( RR: 0.64, P < 0.0001) agents. Risk reduction was greater with novel vs. non-novel agents ( PFS: P = 0.047; OS: P = 0.058). Conclusions Achieving CR during first-line therapy remains important in the novel-agent era; magnitude of association between achieving CR and outcomes appears higher for CR obtained using novel vs. non-novel agents. [ABSTRACT FROM AUTHOR]