Deeper response predicts better outcomes in high-risk smoldering multiple myeloma: results of the I-PRISM phase II clinical trial

Rákkutatás · Multiple myeloma · KRAS · TP53

Deep responses significantly improve time to progression in high‑risk smoldering multiple myeloma.

Early therapeutic intervention in high‑risk smoldering multiple myeloma (HR‑SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long‑term outcomes. The single‑arm I‑PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR‑SMM. The primary endpoint, median progression‑free survival (PFS), was not reached (NR) (95% CI: 57.7–NR, median follow‑up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9–NR) and coincided with or preceded SLiM‑CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM‑CRAB and biochemical progression. MRD‑negativity (10‑^5 sensitivity) predicted a 5‑year biochemical PFS of 100% versus 40% in MRD‑positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single‑cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes.

This study demonstrates that deep biochemical responses correlate with prolonged progression‑free survival, supporting early intervention strategies in high‑risk smoldering multiple myeloma.

Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.

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