Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US.

Aged Antibodies, Monoclonal / therapeutic use Antineoplastic Combined Chemotherapy Protocols / therapeutic use Boron Compounds / therapeutic use Bortezomib / therapeutic use Female Glycine / analogs & derivatives Humans Male Middle Aged Multiple Myeloma / drug therapy Neoplasm Recurrence, Local / drug therapy Oligopeptides / therapeutic use Retrospective Studies Treatment Outcome

Bortezomib Carfilzomib Daratumumab Ixazomib Lenalidomide Pomalidomide Proteasome inhibitor triplet therapy Real-world Relapsed refractory multiple myeloma

Journal

Annals of hematology

ISSN: 1432-0584

Titre abrégé: Ann Hematol

Pays: Germany

ID NLM: 9107334

Informations de publication

Date de publication:
Sep 2021

Historique:

received: 08 01 2021

accepted: 22 03 2021

pubmed: 11 5 2021

medline: 21 8 2021

entrez: 10 5 2021

Statut: ppublish

Résumé

Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum's deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

Identifiants

DOI: 10.1007/s00277-021-04534-8 PMID: 33970288 PMC: PMC8357697

pubmed: 33970288

doi: 10.1007/s00277-021-04534-8

pii: 10.1007/s00277-021-04534-8

pmc: PMC8357697

doi:

Substances chimiques

Antibodies, Monoclonal 0

Boron Compounds 0

Oligopeptides 0

daratumumab 4Z63YK6E0E

Bortezomib 69G8BD63PP

ixazomib 71050168A2

carfilzomib 72X6E3J5AR

Glycine TE7660XO1C

Types de publication

Comparative Study Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

2325-2337

Informations de copyright

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