Anti-CD38 monoclonal antibodies in multiple myeloma with gain/amplification of chromosome arm 1q: a review of the literature.

Enrica Antonia Martino, Ernesto Vigna, Fortunato Morabito, Emiliano Barbieri, Massimo Gentile, Antonino Neri, Micol Quaresima, Elena Rivolti

Journal: Expert opinion on biological therapy 2024;24(5):365-381

PMID: 38757726

Abstract

INTRODUCTION

Gain/amplification of 1q (+1q) represents one of the most prevalent cytogenetic abnormalities (CAs) observed in multiple myeloma (MM). Historical studies predating the advent of anti-CD38 monoclonal antibodies (moAbs) implicated + 1q in poor prognoses, prompting its integration into novel staging systems. However, with the emergence of daratumumab and isatuximab, two pivotal anti-CD38 moAbs, the landscape of MM therapy has undergone a profound transformation.

AREAS COVERED

This review encompasses a comprehensive analysis of diverse study methodologies, including observational investigations, clinical trials, meta-analyses, and real-world database analyses. By synthesizing these data sources, we aim to provide an overview of the current understanding of + 1q in the context of anti-CD38 moAbs therapies.

EXPERT OPINION

Despite the paucity of available data, evidence suggests a potential mitigating effect of daratumumab on the adverse prognostic implications of + 1q. However, this benefit seems to diminish in patients harboring ≥ 4 copies or with concurrent high-risk CAs. On the other hand, isatuximab demonstrated promising outcomes in the relapsed-refractory setting for + 1q MM patients. Nevertheless, direct comparison between the two compounds is currently challenging. The current evidence firmly supports the integration of anti-CD38 moAb-based therapies as the standard of care for + 1q patients, pending further elucidation.

Address: Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.; Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.; Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy.; Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.; Biotechnology Research Unit, AO of Cosenza, Cosenza, Italy.; Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.; Department of Pharmacy, Health and Nutritional Science, University of Calabria, Rende, Italy.
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