Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial

Thierry Facon*, Shaji K. Kumar, Torben Plesner, Robert Z. Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Joseph R. Mace, Noopur Raje, Mourad Tiab, Margaret Macro, Laurent FrenzelXavier Leleu, Tahamtan Ahmadi, Jianping Wang, Rian Van Rampelbergh, Clarissa M. Uhlar, Brenda Tromp, Maria Delioukina, Jessica Vermeulen, Saad Z. Usmani

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

Background: In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we report the updated efficacy and safety results from a prespecified interim analysis for overall survival. Methods: MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolled patients at 176 hospitals in 14 countries across North America, Europe, the Middle East, and the Asia-Pacific region. Eligible patients were aged 18 years or older, had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performance status score of 0–2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation because of their age (≥65 years) or comorbidities. Patients were randomly assigned (1:1) using randomly permuted blocks (block size 4) by an interactive web response system to receive 28-day cycles of intravenous daratumumab (16 mg/kg, once per week during cycles 1–2, once every 2 weeks in cycles 3–6, and once every 4 weeks thereafter) plus oral lenalidomide (25 mg on days 1–21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group) or lenalidomide and dexamethasone alone (control group). Randomisation was stratified by International Staging System disease stage, geographical region, and age. Neither patients nor investigators were masked to treatment assignment. The primary endpoint was progression-free survival, which was centrally assessed, and a secondary endpoint was overall survival (both assessed in the intention-to-treat population). The safety population included patients who received at least one dose of the study treatment. The results presented here are from a prespecified interim analysis for overall survival, for which the prespecified stopping boundary was p=0·0414. This trial is registered with ClinicalTrials.gov, NCT02252172. Findings: Between March 18, 2015, and Jan 15, 2017, 952 patients were assessed for eligibility, of whom 737 patients were enrolled and randomly assigned to the daratumumab group (n=368) or the control group (n=369). At a median follow-up of 56·2 months (IQR 52·7–59·9), median progression-free survival was not reached (95% CI 54·8–not reached) in the daratumumab group versus 34·4 months (29·6–39·2) in the control group (hazard ratio [HR] 0·53 [95% CI 0·43–0·66]; p<0·0001). Median overall survival was not reached in either group (daratumumab group, 95% CI not reached–not reached; control group, 95% CI 55·7–not reached; HR 0·68 [95% CI 0·53–0·86]; p=0·0013). The most common (>15%) grade 3 or higher treatment-emergent adverse events were neutropenia (197 [54%] patients in the daratumumab group vs 135 [37%] patients in the control group), pneumonia (70 [19%] vs 39 [11%]), anaemia (61 [17%] vs 79 [22%]), and lymphopenia (60 [16%] vs 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the daratumumab group and 257 (70%) patients in the control group. Treatment-related deaths occurred in 13 (4%) patients in the daratumumab group and ten (3%) patients in the control group. Interpretation: Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns. Our results support the frontline use of daratumumab plus lenalidomide and dexamethasone for patients with multiple myeloma who are ineligible for transplantation. Funding: Janssen Research & Development.

OriginalsprogEngelsk
TidsskriftThe Lancet Oncology
Vol/bind22
Udgave nummer11
Sider (fra-til)1582-1596
ISSN1470-2045
DOI
StatusUdgivet - nov. 2021

Bibliografisk note

Funding Information:
This study was sponsored by Janssen Research & Development. We thank the patients who volunteered to participate in this trial, their families, and the staff members at the trial sites who cared for them; the members of the data and safety monitoring committee (Nikhil C Munshi [chair], Mario DiCato, and Weichung Shih); representatives of the sponsor who were involved in data collection and analyses; Intergroupe Francophone du Myélome for their strong support and guidance during the trial start-up; and Grace Wang and Kimberly Carmony of Cello Health Communications/MedErgy for medical writing and editorial assistance. All authors had access to the data and were not restricted by confidentiality agreements. Professional medical writers who were funded by the sponsor prepared the manuscript. All authors reviewed and revised the manuscript and approved it for submission. The sponsor and authors vouch for the accuracy and completeness of the data from the prespecified interim analysis and for adherence of the trial to the protocol.

Funding Information:
TF received payment or honoraria for speakers bureaus for Bristol Myers Squibb, Janssen, and Takeda; and participated on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Karyopharm, Oncopeptides, Roche, and Takeda. SKK received research funding from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, CARsgen, Janssen, Molecular Templates, Novartis, Roche-Genentech, Takeda, and TeneoBio; and consulted for or participated on an advisory board for AbbVie, Amgen, Antengene, AstraZeneca, BeiGene, bluebird bio, Bristol Myers Squibb, Epizyme, Janssen, Oncopeptides, Roche-Genentech, Secure Biotherapeutics, and Takeda. TP received consulting fees from Celgene and Janssen; received payment or honoraria for educational events from Janssen; received payment for expert testimony from CSL Behring, Oncopeptides, and Takeda; and holds stock or stock options in Novo Nordisk. RZO received support for the present manuscript from Janssen; received laboratory research funding from Asylia Therapeutics, BioTheryX, and Heidelberg Pharma; received clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, and Takeda; received royalties or licenses for, has patents planned, issued or pending for, and holds stock or stock options in Asylia Therapeutics; received consulting fees from EcoR1 Capital; and participated on an advisory board for Amgen, BioTheryX, Bristol Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis, Janssen Biotech, Juno Therapeutics, Karyopharm, Kite, Neoleukin, Oncopeptides, Regeneron, Sanofi-Aventis, Servier, and Takeda. PM received honoraria from AbbVie, Amgen, Celgene, Janssen, Oncopeptides, and Sanofi. NB received research funding from Celgene, Janssen, and Pfizer; participated on an independent review committee for Janssen, Karyopharm, and Legend Biotech; received honoraria for educational events from Bristol Myers Squibb, Celgene, and Janssen; and participated on an advisory board for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Pfizer, Sanofi, and Takeda. HQ received grants or contracts from Amgen, Celgene, GlaxoSmithKline, Karyopharm, and Sanofi; and had a leadership or fiduciary role in advisory boards for Amgen, Celgene, CSL Behring, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, and Takeda. HG received grants or contracts from Amgen, Bristol Myers Squibb, Celgene, Chugai, Dietmar-Hopp-Foundation, Janssen, Johns Hopkins University, and Sanofi; received consulting fees from Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; received payment or honoraria for lectures and presentations from Amgen, Art Tempi, Bristol Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Novartis, and Sanofi; received support for attending meetings or travel, or both, from Adaptive Biotechnologies, Amgen, Art Tempi, Bristol Myers Squibb, Celgene, Chugai, Janssen, Sanofi, and Takeda; and received research support from Amgen, Bristol Myers Squibb, Celgene, Chugai, Incyte, Janssen, Merck Sharp & Dohme, Molecular Partners, MundiPharma, Novartis, Sanofi, and Takeda. MOD received consulting fees from Janssen; has several patents planned, issued, or pending relating to the use of natural killer cells and sialyltransferase inhibition in the treatment of cancer; participated on an advisory board for Amgen, Celgene, and Janssen; serves as a director of ONK Therapeutics; and holds stock or stock options in ONK Therapeutics and Carrick Therapeutics. AP received grants or contracts from Sanofi and Takeda; received payment or honoraria for presentations and educational events from AbbVie, Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda; received payment or honoraria for a speakers bureau from Janssen and Sanofi; received support for attending meetings or travel, or both, from Amgen and Janssen; and participated on a data safety monitoring board or advisory board for Janssen and Sanofi. CPV received honoraria from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, Sanofi, and Takeda. KW received honoraria from AbbVie, Adaptive Biotechnologies, Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, and Takeda; and received grants from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, and Sanofi. NR served in an advisory role for Amgen, bluebird bio, Caribou, GlaxoSmithKline, and Immuneel. MM received research funding from Janssen and Takeda; received honoraria from GlaxoSmithKline, Janssen, Sanofi, and Takeda; and received travel accommodations from Janssen and Takeda. LF received support for attending meetings or travel, or both, from Amgen and Janssen; and received payment or honoraria for educational events from Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, and Takeda. TA is an employee of and holds equity in Genmab. JW and RVR are employees of Janssen. CMU, BT, MD, and JV are employees of Janssen; and hold equity in Johnson & Johnson. SZU received grants from Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda; and received personal fees from AbbVie, Amgen, Celgene, Genentech, Gilead, GlaxoSmithKline, Janssen, Merck, MundiPharma, Oncopeptides, Sanofi, Seattle Genetics, SkylineDX, and Takeda. SB, HN, CH, JRM, MT, and XL declare no competing interests.

Publisher Copyright:
© 2021 Elsevier Ltd

Fingeraftryk

Dyk ned i forskningsemnerne om 'Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial'. Sammen danner de et unikt fingeraftryk.

Citationsformater