Treatment of primary plasma cell leukaemia with carfilzomib and lenalidomide-based therapy (EMN12/HOVON-129): final analysis of a non-randomised, multicentre, phase 2 study.

BACKGROUND

Primary plasma cell leukaemia is a rare and aggressive plasma cell disorder with a poor prognosis. The aim of the EMN12/HOVON-129 study was to improve the outcomes of patients with primary plasma cell leukaemia by incorporating carfilzomib and lenalidomide in induction, consolidation, and maintenance therapy.

METHODS

The EMN12/HOVON-129 study is a non-randomised, phase 2, multicentre study conducted at 19 academic centres and hospitals in seven European countries (Belgium, Czech Republic, Denmark, Italy, Norway, The Netherlands, and the UK) for previously untreated patients with primary plasma cell leukaemia aged 18 years or older. Inclusion criteria were newly diagnosed primary plasma cell leukaemia (defined as >2 ×10

FINDINGS

Between Oct 23, 2015, and Aug 5, 2021, 61 patients were enrolled and received KRd induction treatment (36 patients aged 18-65 years [20 (56%) were male and 16 (44%) female], and 25 aged ≥66 years [12 (48%) were male and 13 (52%) female]). With a median follow-up of 43·5 months (IQR 27·7-67·8), the median progression-free survival was 15·5 months (95% CI 9·4-38·4) for younger patients. For older patients, median follow-up was 32·0 months (IQR 24·7-34·6), and median progression-free survival was 13·8 months (95% CI 9·2-35·5). Adverse events were most frequently observed directly after treatment initiation, with infections (two of 36 (6%) younger patients and eight of 25 (32%) older patients) and respiratory events (two of 36 [6%] younger patients and four of 25 [16%] older patients) being the most common grade 3 or greater events during the first four KRd cycles. Treatment-related serious adverse events were reported in 26 (72%) of 36 younger patients and in 19 (76%) of 25 older patients, with infections being the most common. Treatment-related deaths were reported in none of the younger patients and three (12%) of the older patients (two infections and one unknown cause of death).

INTERPRETATION

Carfilzomib and lenalidomide-based therapy provides improved progression-free survival compared with previously published data. However, results remain inferior in primary plasma cell leukaemia compared with multiple myeloma, highlighting the need for new studies incorporating novel immunotherapies.

FUNDING

Dutch Cancer Society, Celgene (a BMS company), and AMGEN.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests NWCJvdD reports research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, Cellectis and BMS, and advisory board role with Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, Bayer, Pfizer, Abbvie, Adaptive, and Servier, all paid to employer. MCM reports research support from Beigene; consultancy or advisory roles with Janssen, GSK, and CDR-life; honoraria from BMS, Pfizer, Janssen, and Medscape; and data safety monitoring board role for BMS, all paid to employer. BvdH reports honoraria for data safety monitoring board membership from the Intergroupe Francophone du Myélome. FS reports research support from Celgene, Janssen, Oncopeptides, Sanofi, GSK, and Targovax; honoraria from Amgen, BMS, Takeda, Abbvie, Janssen, Novartis, SkyliteDX, Oncopeptides, Sanofi, Pfizer, Daiki-Sankyo, and GSK; and participated on a data safety monitoring board or advisory board for Abbvie, GSK, Celgene, Takeda, Janssen, Oncopeptides, Sanofi, and BMS. KLW has served in advisory boards for Janssen and Pfizer. AB received honoraria and served in advisory boards from BMS, Janssen, Amgen, and Sanofi. WWHR reports honoraria from Amgen and SANOFI, all paid to employer; support for travel from Takeda and Abbvie; and advisory board participations for BMS/Celgene, and Janssen, all paid to employer. VHJvdV reports a Laboratory Services Agreement with BD Biosciences, Cytognos, and Agilent, all paid to employer. TL has received research grants from Takeda, AMGEN, and Janssen, honoraria from AMGEN, Janssen, BMS, and Pfizer; traveling support from Pfizer and Janssen; and equipment from Takeda and Pfizer. MO has received honoraria and served in advisory board for AbbVie, Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. PT has received honoraria from Janssen, BMS/Celgene, GlaxoSmithKline, Takeda, Amgen, Sanofi, Pfizer, and AbbVie and support for traveling from Janssen, BMS/Celgene, Sanofi, and AMGEN. KM has received honoraria from GSK, Janssen, Pfizer, and Sanofi; support for traveling from Sanofi; and participates on an advisory board for Pfizer. JC has received research funding from Janssen, honoraria from AMGEN and Janssen, and support for travel from GILEAD. SZ has received research funding from Takeda and Janssen and serves in advisory boards for Janssen, Takeda, and BMS, all paid to institution. RH has received research funding from Janssen, AMGEN, Celgene/BMS, Novartis, and Takeda, all paid to employer; consulting fees from Janssen, AMGEN, Celgene, Abbvie, BMS, Novartis, Pharmamar, and Takeda; honoraria from Janssen, AMGEN, Celgene, BMS, Pharmamar, and Takeda; support for attending meetings from AMGEN, Celgene, Takeda, and Janssen; and has participated on advisory boards from BMS, Takeda, AMGEN, Oncopeptides, Sanofi, Janssen, and GSK. RB reports educational grant from BMS/Celgene. AJV reports honoraria from BMS. MB reports research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, BMS, and Mundipharma; honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, BMS, and Abbvie; and advisory board role for Janssen. FG reports honoraria from Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, GlaxoSmithKline, data safety monitoring board or advisory board participation for Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, GlaxoSmithKline, Roche, Adaptive Biotechnologies, Oncopeptides, bluebird bio, and Pfizer. PS reports advisory board roles with Amgen, BMS, Celgene, Janssen, Karyopharm, and Pfizer and research funding from Amgen, BMS, Celgene, Janssen, Karyopharm, and Pfizer. PM reports honoraria from or Advisory Board role with AMGEN and BMS. All other authors declare no competing interests.