(PA-506) Isatuximab Subcutaneous via an On-body Injector Plus Pomalidomide-dexamethasone in Relapsed/refractory Multiple Myeloma: Subgroup Analysis by Prior Lines of Therapy from the Phase 3 IRAKLIA Trial

RRMM pts ≥18 years (y) were randomized 1:1 to Isa SC OBI (1400 mg; n=263) or IV (10 mg/kg; n=268) weekly in Cycle 1, then every 2 weeks with Pd. ORR was a co-primary endpoint (stratification factors included number of prior LOT [1-2 vs ≥3]).

Results: Baseline characteristics were balanced across prior LOT subgroups for Isa SC OBI vs IV: median age was 66-67 y for 1 prior LOT and 66 y for >1 LOT. The >1 LOT group had a median of 3 prior LOT. Isa-Pd demonstrated efficacy regardless of the number of LOT; ORRs for Isa SC OBI vs IV were 74% vs 76% (1 prior LOT) and 70% vs 68% ( >1 prior LOT) (Table). Among 1 prior LOT pts, 95% (Isa SC OBI) and 90% (Isa IV) were LEN-refractory; among >1 prior LOT pts, 59% (Isa SC OBI) and 52% (Isa IV) of pts were LEN-refractory at last regimen. For pts who were LEN-refractory at last regimen, ORRs for Isa SC OBI vs IV were 72% vs 74% (1 LOT) and 68% vs 62% ( >1 LOT); for 1 prior LOT, rates of ≥ very good partial response (≥VGPR) and ≥ complete response (≥CR) for Isa SC OBI vs IV were 42% vs 51% and 15% vs 17%, respectively; for >1 prior LOT, rates were 40% vs 45% (≥VGPR), and 17% vs 20% (≥CR). Among all pts being assessed according to prior LOT, Grade ≥3 treatment-emergent adverse events (TEAE) for Isa SC OBI vs IV were 74% vs 68% (1 LOT) and 85% vs 80% ( >1 LOT), with rates of treatment discontinuation due to TEAE of 7% vs 5% (1 LOT) and 9% vs 10% ( >1 LOT).

Conclusions:

In IRAKLIA, comparable results were observed between the Isa SC OBI + Pd and Isa IV + Pd arms regardless of the number of prior LOT, demonstrating efficacy of Isa-Pd in the ≥1 prior LOT and LEN-refractory settings. These findings support use of Isa SC administered by the novel OBI plus Pd in RRMM pts regardless of number of prior LOT.

Table