Impact of prior lenalidomide or proteasome inhibitor exposure on the effectiveness of ixazomib–lenalidomide–dexamethasone for relapsed/refractory multiple myeloma: A pooled analysis from the INSURE study

• Published in: European journal of haematology Vol. 113; no. 2; pp. 190 - 200
• Main Authors: Lee, Hans C., Ramasamy, Karthik, Macro, Margaret, Davies, Faith E., Abonour, Rafat, Rhee, Frits, Hungria, Vania T. M., Puig, Noemi, Ren, Kaili, Silar, Jiri, Enwemadu, Victoria, Cherepanov, Dasha, Leleu, Xavier
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2024
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Boron Compounds - administration & dosage; Boron Compounds - adverse effects; Boron Compounds - therapeutic use; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Drug Resistance, Neoplasm; effectiveness; Female; Glycine - administration & dosage; Glycine - adverse effects; Glycine - analogs & derivatives; Glycine - therapeutic use; Humans; Immunotherapy; ixazomib; lenalidomide; Lenalidomide - administration & dosage; Lenalidomide - adverse effects; Lenalidomide - therapeutic use; Male; Middle Aged; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; prior treatment exposure; proteasome inhibitor; Proteasome inhibitors; Proteasome Inhibitors - administration & dosage; Proteasome Inhibitors - adverse effects; Proteasome Inhibitors - therapeutic use; Proteasomes; Recurrence; relapsed/refractory; Retreatment; Targeted cancer therapy; Treatment Outcome; Uvea; effectiveness; multiple myeloma; proteasome inhibitor; ixazomib; relapsed/refractory; lenalidomide; prior treatment exposure
• ISSN: 0902-4441; 1600-0609; 1600-0609
• DOI: 10.1111/ejh.14214

Objectives To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib–lenalidomide–dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM). Methods INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA‐IXA, and REMIX. Results Overall, 391/100/68 were lenalidomide‐naïve/−exposed/−refractory and 37/411/110 were PI‐naïve/−exposed/−refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression‐free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide‐naïve/exposed/refractory patients. Median DOT and PFS in PI‐naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide‐naïve/exposed/refractory patients in INSIGHT and UVEA‐IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI‐naïve/exposed/refractory patients in INSIGHT and UVEA‐IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable. Conclusion IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide‐ and/or PI‐nonrefractory versus refractory patients.