Comparative analysis of subcutaneous Isa VRd (ISASOCUT) and intravenous Isa VRd (IMROZ) in transplant-ineligible newly diagnosed multiple myeloma across age groups.

Abstract

7561 Background: Intravenous (IV) isatuximab (Isa) plus bortezomib, lenalidomide, and dexamethasone (VRd) significantly improved PFS in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (Ti NDMM) in the IMROZ randomized Phase (Ph) 3 study (NCT03319667). Efficacy and safety of subcutaneous (SC) Isa VRd, using an innovative on-body injector (OBI), has been demonstrated previously, including in Ti NDMM pts in the ISASOCUT Ph2 study (NCT05889221). Bortezomib was administered twice weekly (BIW) in IMROZ vs weekly in ISASOCUT. Here, safety and efficacy of Isa OBI VRd (ISASOCUT) and Isa IV VRd (IMROZ) are evaluated at 8 months (mos) follow-up. Methods: This analysis included 74 pts from ISASOCUT (Isa OBI VRd) and 265 from IMROZ (Isa IV VRd). Isa OBI VRd pts received Isa 1400 mg (weekly cycle [C]1, then every 2 weeks [Q2W] up to C12, and Q4W thereafter); each cycle lasted 28 days. SC bortezomib (1.3 mg/m 2 ) was given BIW in C1 and weekly thereafter. Isa IV VRd pts received Isa 10 mg/kg weekly in C1, then Q2W, followed by Q4W from C18 onwards. SC bortezomib (1.3 mg/m 2 ) was given BIW from C1-4. C1-4 lasted 42 days, with the remainder lasting 28 days each. This comparative analysis evaluated safety and efficacy at 8 mos follow-up by baseline age group (<75 yrs, ≥75 yrs). Results: Baseline demographic and disease characteristics were similar between Isa OBI VRd and Isa IV VRd pts. Incidence of serious TEAEs were similar between groups (35.1% and 42.2% for Isa OBI VRd and Isa IV VRd, respectively) and across age groups. The rate of systemic infusion reaction was lower with Isa OBI VRd vs Isa IV VRd (4 [5%] vs 60 [22.8%]). Grade (G) ≥3 neutropenic complications occurred in 2.7% Isa SC OBI pts and 3.8% Isa IV pts and were similar across age groups (<75 yrs, 2% vs 4.1%; ≥75 yrs, 4% vs 2.9%). Study discontinuation due to TEAEs occurred in 2.7% Isa SC OBI pts and 8.7% Isa IV pts, with lower rates in Isa SC OBI (<75 yrs, 0% vs 8.2%; ≥75 yrs, 8% vs 10.3%). Across both age groups, a lower incidence of G2 peripheral neuropathy (PN) was observed with Isa OBI VRd (weekly V) vs Isa IV VRd (BIW V) (<75 yrs, 20.4% vs 28.7%; ≥75 yrs, 20% vs 35.3%) as well as G≥3 PN (<75 yrs, 2% vs 9.2%; ≥75 yrs, 0% vs 7.4%). Isa OBI VRd (weekly V) was associated with less bortezomib dose reduction due to nervous system disorders (Isa OBI VRd [weekly V] vs Isa IV VRd [BIW V]: <75 yrs, 14.3% vs 37.4%; ≥75 yrs, 28.0% vs 35.3%). ≥VGPR rates for Isa OBI VRd and Isa IV VRd were 87.8% and 83.2%, respectively (RR: 1.055; 95% CI: 0.934-1.192), in pts aged <75 yrs and 80.0% and 82.6%, respectively (RR: 0.968; 95% CI: 0.774-1.211), in pts aged ≥75 yrs. Conclusions: In this comparative analysis, Isa OBI VRd with weekly bortezomib (ISASOCUT) is more tolerable for pts regarding PN than the BIW schedule (IMROZ). Both groups maintained similar ≥VGPR rates across age groups. These findings support the efficacy and safety of the Isa SC OBI with weekly bortezomib. Clinical trial information: NCT05889221 and NCT03319667 .