Dynamic cytogenetic evolution in multiple myeloma: prognostic implications from diagnosis to first relapse

Cytogenetic abnormalities (CAs) in multiple myeloma (MM) are traditionally assessed statically at diagnosis, but longitudinal monitoring reveals dynamic clonal evolution, particularly during relapse. In Asian populations, data on CA dynamics and their prognostic impact remain scarce.

This retrospective study included 106 MM patients (2014-2024) in whom CAs were evaluated at diagnosis and relapse via cIg-FISH. The prognostic impact of clonal burden, copy number alterations, and longitudinal evolution of cytogenetic complexity was comprehensively assessed.

At first relapse, 33.0% of patients acquired new CAs, with 1q21+ and del(17p13) incidences significantly increasing (P = .032, P = .003). Longitudinal analysis showed 1q21 amplification (≥4 copies) expanded (27.4%-40.6%), while gain (3 copies) remained stable. Baseline 1q21 amplification predicted shorter 1st PFS (P = .002), whereas 1q21 gain at relapse correlated with inferior 2nd PFS (P = .023), often co-occurring with del(17p13) (28.1%). Persistent 1q21+ and de novo del(17p13) both predicted inferior OS (P < .05). Based on clonal dynamics, patients with >20% expansion exhibited significantly shorter 1st PFS (P = .045) compared to the stable (unchanged) CAs subgroup. Similarly, those acquiring new CAs had shorter 2nd PFS (P = .039) and a trend toward worse OS (P = .056).

Both acquisition of new CAs and expansion of existing clones at relapse are key prognostic indicators, highlighting the importance of dynamic CA monitoring in MM management.