Late versus early response and depth of response are associated with improved outcomes in patients with newly diagnosed multiple myeloma enrolled in the TOURMALINE-MM2 trial.

Abstract

Deeper responses are associated with longer survival in multiple myeloma (MM); however, limited data exist on the impact of response kinetics on outcomes. We investigated progression-free survival (PFS) and duration of response (DOR) by response depth and in early (best confirmed response 0-4 months; n=424) versus late responders (best confirmed response>4 months; n=281). Newly diagnosed patients enrolled in TOURMALINE-MM2 receiving ixazomib-lenalidomide-dexamethasone (IRd) (n=351) or placebo-Rd (n=354) were evaluated post hoc. Deeper responses were associated with longer PFS (complete response [CR] not reached [NR], very good partial response [VGPR] 37.2 months, partial response [PR] 16.4 months) and DOR (CR NR, VGPR 42.6 months, PR 15.4 months). Among patients with a PFS (n=511) or DOR (n=484) of ≥6 months who achieved ≥PR, median PFS was prolonged among late versus early responders receiving IRd (59.7vs. 17.9 months) or placebo-Rd (56.6vs. 12.4 months), as was median DOR (IRd, NR vs. 20.9 months; placebo-Rd, 58.2vs. 11.7 months). While the treatment paradigm for newly diagnosed MM is treatment to progression, our findings suggest slowness of response to a proteasome inhibitor-immunomodulatory drug-steroid combination is not a negative predictor of outcome.