Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study.

BACKGROUND

Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138 and synergistically enhances the antitumor activity of lenalidomide in preclinical models of multiple myeloma. This phase 1/2a study was done to determine the safety, activity, and pharmacokinetics of indatuximab ravtansine in combination with immunomodulatory drugs in patients with relapsed or refractory multiple myeloma.

METHODS

This open-label, phase 1/2a study took place at nine hospital sites in the USA. Eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and ECOG performance status or Zubrod score of 2 or below. Patients who received indatuximab ravtansine with lenalidomide and dexamethasone (indatuximab ravtansine plus lenalidomide) had failure of at least one previous therapy. Patients treated with indatuximab ravtansine with pomalidomide and dexamethasone (indatuximab ravtansine plus pomalidomide) had failure of at least two previous therapies (including lenalidomide and bortezomib) and had progressive disease on or within 60 days of completion of their last treatment. In phase 1, patients received indatuximab ravtansine intravenously on days 1, 8, and 15 of each 28-day cycle in escalating dose levels of 80 mg/m

FINDINGS

64 (86%) of 74 screened patients were enrolled between July 3, 2012, and June 30, 2015. 47 (73%) patients received indatuximab ravtansine plus lenalidomide (median follow-up 24·2 months [IQR 19·9-45·4]) and 17 (27%) received indatuximab ravtansine plus pomalidomide (24·1 months [17·7-36·7]). The maximum tolerated dose of indatuximab ravtansine plus lenalidomide was 100 mg/m

INTERPRETATION

Indatuximab ravtansine in combination with immunomodulatory drugs shows preliminary antitumor activity, is tolerated, and could be further evaluated in patients with relapsed or refractory multiple myeloma.

FUNDING

Biotest AG.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests KRK received honoraria from Incyte, Bayer, Janssen, Novartis, Celgene, Epizyme, Pharmacyclics, Karyopharm and Gilead, consulting fees from Takeda, AstraZeneca, Sanofi-Aventis, Denovo Biopharma, Verastem, and Amgen, and received research funding from Takeda. SA received consulting fees or honoraria from Celgene, Takeda, Amgen, Janssen, Beigene, GSK, Oncopeptides, and Novartis. DSS had a membership on an entity's advisory committee with Celgene, BMS, GSK, Takeda, Karyopharma, Cellularity, Janssen, Amgen, and Merck. SJ received honorarium and participated in advisory boards for Karyopharm Therapeutics, Legend Biotech, Takeda, Celgene, BMS, and Janssen. NCM was a consultant for Celgene, Merck, Pfizer, Takeda, OncoPep, Janssen and Biotest, and is a part owner of OncoPep. SM received speaker fees from Takeda, Janssen, Amgen, Karyopharm, BMS, and GSK, and received support for attending meetings or travel from Merck, and participated in advisory boards for Amgen, Sanofi, Bristol-Meyers Squibb, Janssen, GSK, and Takeda. AC-K participated in an advisory board for OncoPep. SL received honoraria from Celgene, Takeda, Novartis, Janssen, Amgen, BMS, and GSK, and receive consultancy fees from Celgene, Takeda, Novartis, Janssen, Amgen, BMS, and GSK. MR, FB-R., AA-B, FR, EH-K, TH and AW-D are or were employees of Biotest. KCA received advisory board fees from BMS, Celgene, Gilead, and Millennium Pharmaceuticals, holds a leadership or fiduciary role in Starton, Raqia, and NextRNA, and is the scientific founder of C4 Therapeutics and OncoPep. SC, AM, GS, and TZ have no interests to declare.