Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial
Abstract
AbstractEarly 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.
Article Details
Authors (22)
Omar Nadeem
Michelle P. Aranha
Robert Redd
Michael Timonian
Sophie Magidson
Elizabeth D. Lightbody
Jean-Baptiste Alberge
Luca Bertamini
Ankit K. Dutta
Habib El-Khoury
Mark Bustoros
Jacob P. Laubach
Giada Bianchi
Elizabeth O’Donnell
Ting Wu
Children’s Hospital, Zhejiang University School of Medicine
Junko Tsuji
Kenneth C. Anderson
Gad Getz
Lorenzo Trippa
From Médecins Sans Frontières (L.G., F.V.), Sorbonne Université, INSERM Unité 1135, Centre d’Immunologie et des Maladies Infectieuses (L.G.), Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié–Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (L.G.), and Epicentre (M.G., E. Baudin), Paris, and Translational Research on HIV and Endemic and Emerging Infectious Diseases, Montpellier Université de Montpellier, Montpellier, Institut de Recherche pour le Développement, Montpellier, INSERM, Montpellier (M.B.) — all in France; Interactive Development and Research, Singapore (U.K.); McGill University, Epidemiology, Biostatistics, and Occupational Health, Montreal (U.K.); UCSF Center for Tuberculosis (G.E.V., P.N., P.P.J.P.) and the Division of HIV, Infectious Diseases, and Global Medicine (G.E.V.), University of California at San Francisco, San Francisco; the National Scientific Center of Phth...
Paul G. Richardson
Jerome Lipper Multiple Myeloma Center, Dana–Farber Cancer Institute, Harvard Medical School, Boston
Romanos Sklavenitis-Pistofidis
Irene M. Ghobrial