BRIEF RESEARCH REPORT article
Front. Oncol.
Sec. Hematologic Malignancies
IMPACT OF 1q VULNERABILITIES IN PATIENTS TREATED WITH ANTI-CD38 MONOCLONAL ANTIBODIES
Provisionally accepted
María Sánchez-Tabernero1,2,3*
Irene Zamanillo1,3
Jose Maria Sanchez-Pina1,3
Rafael Alonso Fernández1,3Nieves López-Muñoz1,3
Magdalena Corona De Lapuerta1,3Manuela Fernández-Guijarro4
María-Teresa Cedena1,3Susana Cortijo4María Calbacho1,3Joaquin Martínez-López1,2,3- 1Servicio de Hematología y Hemoterapia, Hospital Universitario 12 de Octubre, Madrid, Spain
- 2Universidad Complutense de Madrid, Madrid, Spain
- 3Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
- 4Hospital Universitario 12 de Octubre, Madrid, Spain
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Multiple myeloma (MM) is a disorder in which cytogenetic abnormalities, including 1q gain or amplification, have been associated with adverse outcomes. We conducted a retrospective single-center study evaluating the impact of +1q in MM patients treated with daratumumab or isatuximab. FISH was performed to detect 1q gain or amplification and other high-risk cytogenetic abnormalities. A total of 149 patients were analyzed (115 receiving daratumumab; 34 isatuximab). In the daratumumab cohort, 51.3% harbored 1q alterations, with comparable baseline characteristics. Patients with 1q alterations had lower MRD negativity (20.3% vs 39.3%; p = 0.04) and a trend toward shorter PFS (26.3 vs 43.4 months; p = 0.05), while OS was similar overall (61.2 vs 68.7 months; p = 0.24), although 1q amplification was associated with poorer OS (42 vs 74 months; p = 0.029). These findings were not confirmed in multivariate analysis, where the line of anti-CD38 therapy emerged as the main variable significantly associated with both PFS and OS. In the isatuximab-treated group, 41% exhibited 1q alterations, with no significant differences in response rates, MRD negativity (28.6% vs 55%; p = 0.171), PFS (56.9 vs 58.2 months; p = 0.67), or OS (median not reached; p = 0.27). Our findings suggest that the poorer outcomes observed in univariate analyses among daratumumab-treated patients likely reflect a more advanced disease and later therapy lines, rather than the isolated effect of 1q alterations. Comprehensive cytogenetic profiling and achieving MRD negativity remain critical for risk stratification and optimizing therapeutic strategies in patients receiving anti-CD38 therapies.
Keywords: 1q, CD38, Daratumumab, isatuximab, Multiple Myeloma
Received: 01 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Sánchez-Tabernero, Zamanillo, Sanchez-Pina, Alonso Fernández, López-Muñoz, Corona De Lapuerta, Fernández-Guijarro, Cedena, Cortijo, Calbacho and Martínez-López. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: María Sánchez-Tabernero
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