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

Author:

Lee Hans C.1ORCID,Ramasamy Karthik2ORCID,Macro Margaret3,Davies Faith E.4,Abonour Rafat5,van Rhee Frits6,Hungria Vania T. M.7,Puig Noemi8,Ren Kaili9,Silar Jiri10,Enwemadu Victoria11,Cherepanov Dasha9,Leleu Xavier12

Affiliation:

1. Department of Lymphoma/Myeloma The University of Texas MD Anderson Cancer Center Houston Texas USA

2. Department of Haematology Oxford University Hospitals NHS Foundation Trust Oxford Oxfordshire UK

3. CHU de Caen Normandie Caen France

4. Perlmutter Cancer Center, NYU Langone New York City New York USA

5. Indiana University School of Medicine Indianapolis Indiana USA

6. University of Arkansas for Medical Sciences (UAMS) Little Rock Arkansas USA

7. Clinica São Germano and Santa Casa Medical School São Paulo Brazil

8. Hematology Department Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL‐CSIC), CIBERONC Salamanca Spain

9. Takeda Development Center Americas, Inc. (TDCA) Lexington Massachusetts USA

10. Institute of Biostatistics and Analyses, Ltd Brno Czech Republic

11. Takeda Pharmaceuticals U.S.A., Inc. Lexington Massachusetts USA

12. Pôle Régional de Cancérologie, Department of Hematology CHU La Milétrie‐Poitiers Poitiers France

Abstract

AbstractObjectivesTo 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).MethodsINSURE 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.ResultsOverall, 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.ConclusionIRd 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.

Publisher

Wiley

Reference30 articles.

1. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

2. Real‐world duration of treatment (DOT) with lenalidomide‐dexamethasone (rd)‐based regimens in patients (pts) with relapsed/refractory multiple myeloma (RRMM): outcomes from the global INSIGHT MM study;Puig N;HemaSphere,2021

3. Effectiveness and safety of ixazomib‐based therapy in relapsed/refractory multiple myeloma (MM) outside of a clinical trial: final analysis of the ‘use via early access to ixazomib’ (UVEA IXA) study;Ludwig H;HemaSphere,2021

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