Prognostic Impact of Chromosome 1q Gain/Amplification in Multiple Myeloma Treated With Daratumumab-Based Regimens.

Abstract

Gain/amplification of chromosome arm 1q (+1q) is among the most frequent cytogenetic abnormalities (CAs) in multiple myeloma (MM), and a recognized marker of poor prognosis, now integrated into modern risk stratification systems. The advent of anti-CD38 monoclonal antibodies, particularly daratumumab, has significantly improved outcomes. However, the prognostic impact of +1q under daratumumab-based treatments (DBTs) remains uncertain, since pivotal trials rarely reported +1q-specific outcomes, and available real-world data are limited and inconsistent. We conducted a single-center retrospective study of 174 MM patients treated with DBTs between 2018 and 2023 to evaluate the prognostic effect of +1q. By FISH cytogenetic assessment we identified standard-risk (SR), isolated +1q, +1q plus additional high-risk CAs (+1q + HiRCAs), and non-1q HiRCAs groups. The primary endpoint was progression-free survival (PFS); secondary endpoints were time to next treatment (TTNT) and overall survival (OS). Median age was 72.0 years, median line of DBT administration was 2, and 125 patients (71.8%) received daratumumab-lenalidomide-dexamethasone (DaraRd). Cytogenetic data were available for 92 patients (52.9%): 43 SR, 11 non-1q HiRCAs, 18 isolated +1q and 20 +1q + HiRCAs. After a median follow-up of 30.7 months, isolated +1q was associated with significantly shorter PFS (HR 4.77, 95% CI: 1.68-13.53) and TTNT (HR 3.83, 95% CI: 1.33-11.09) versus SR, while +1q + HiRCAs had the worst outcomes across all endpoints (PFS HR 7.67; TTNT HR 5.81; OS HR 6.03). Multivariate analysis confirmed isolated +1q as an independent predictor of inferior PFS (HR 4.56, 95% CI: 1.61-12.95) and TTNT (HR 3.64, 95% CI: 1.26-10.55), with +1q + HiRCAs conferring the highest risks on all outcomes (PFS HR 8.36; TTNT HR 6.37; OS HR 6.18). Findings were consistent in the DaraRd subgroup. These findings demonstrate that +1q retains prognostic significance in the era of DBTs. Isolated +1q remains an independent factor of adverse prognosis, further worsened by co-existing HiRCAs.