Hematologist Hematología Hospital 12 de Octubre, Madrid, Spain, Spain
Introduction: Gain and amplification of 1q21 have been proposed as prognostic markers in patients with multiple myeloma, and there is evidence that these alterations may be associated with worse responses to anti-CD38 monoclonal antibodies (1, 2, 3). In this study, we analyzed the effect of 1q alterations on the prognosis of patients with multiple myeloma treated with isatuximab and daratumumab.
Methods: We collected retrospective data from 117 patients treated with daratumumab at our center. Patients were considered eligible if they had cytogenetic studies and response evaluation. +1q alterations were classified as gain if 3 copies of the gene were found and amplification if 4 or more copies were present determined by FISH.
Results: The median age at diagnosis was 66 years, and 54.7% were women. A total of 23.1% had high-risk ISS-R at diagnosis, and 16.2% had extramedullary involvement. Most of the cohort (80 patients, 68.4%) were relapsed or refractory to previous lines, and received daratumumab therapy after a median of 1 previous line (0-6). In the majority of the cases, daratumumab was administered in combination with other anti-myeloma agents, and only 14.5% of patients received it as monotherapy. A total of 26.5% of patients had 1q gain, and 24.7% had amplification. Overall, the progression-free survival (PFS) in the group of patients with 1q gain or amplification was 14 months compared to 28 months in those without any alteration in 1q, showing a hazard ratio (HR) for PFS of 1.75 (CI 1.05-2.88). Analyzing patients with gain and amplification separately, only patients with 1q amplification maintained a statistically significant difference in the risk of progression (12 vs 28 months; p=0.019; HR 1.9, CI 1.06-3.40), while patients with 1q gain showed a non-significant trend towards shorter PFS (19 vs 28 months; p=0.084; HR 1.6, CI 0.9-2.9). The influence of 1q alterations on progression remained significant in the multivariate analysis, including other cytogenetic abnormalities (del17p, t(4;14); t(14;16), del1p) (p=0.011). The differences in PFS, however, did not translate into a shorter overall survival (OS).
Conclusions: The presence 1q amplification is a poor prognostic factor in patients with multiple myeloma treated with daratumumab and it was associated with shorter PFS in our cohort. Patients with 1q gain showed a trend towards shorter PFS, although it did not reach statistical significance. A larger sample size is needed to confirm this findings.
