Cytogenetic Features and Their Implications in Clinical Practice: A Real-World Analysis of a Large Cohort of Multiple Myeloma Patients

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We retrospectively analysed cytogenetics by fluorescence in situ hybridization (FISH) in 1.026 patients with multiple myeloma treated in real-world with the aim to establish its role in daily clinical practice. Thirty-seven percent of patients had no FISH data available. Based on median PFS of each cytogenetic abnormality found, we identified 3 group of patients with a significantly different PFS and determined which patients can best benefit from anti-CD38 regimens and double transplant. These findings support cytogenetic testing in all patients at diagnosis. BACKGROUND: Cytogenetics by fluorescence in situ hybridization (FISH) plays an increasing prognostic role in multiple myeloma (MM). METHODS: we analysed cytogenetics and its implications in 1.026 patients treated in real-world from 2019 to 2023. Low-risk (LR) patients had normal cytogenetic or del(13q); intermediate-risk (IR) had t(11;14), hyperdiploidy, gain(1q) or del(1p); high-risk (HR) group had del(17p)/TP53, amp1q21, t(4;14), t(14:16) or t(14;20). Co-existence of 2 high risk abnormalities was named double hit. RESULTS: FISH data were not evaluable in 383 patients (37%). Out of 643 evaluable patients, chromosome 1 alterations were observed in 119 (18.5%), high risk chromosome 14 translocations in 65 (10%), del(17p)/TP53 in 37 (6%) and double-hit in 7 patients (1%). Cytogenetic was normal or hyperdiploid in 252 (39%) and 59 (13%) patients, respectively. Median PFS of LR, IR and HR group were 57.5, 43.2 and 30.5 months, respectively (P < .001). Although anti-CD38 regimens resulted in significantly longer PFS in both TE and NTE pts, in the former significant benefit was documented in the LR and IR group but not in HR group while in the latter only in the LR group. Tandem transplantation did not improve PFS both overall and in the 3 risk groups. Multivariate Cox regression analysis selected ECOG-PS ≥2, R-ISS II-III and our cytogenetic score HR as factors affecting PFS. CONCLUSIONS: in real world, more than one third of MM patients do not have baseline FISH data. Nevertheless, cytogenetics and ECOG PS can be used for prognostic staging and for tailoring therapy.

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