P165 | GAIN/AMPLIFICATION OF 1Q IN MULTIPLE MYELOMA PATIENTS TREATED WITH DARATUMUMAB-BASED REGIMENS: A SINGLE-CENTER RETROSPECTIVE STUDY

Gain/amplification of chromosome arm 1q (+1q) is one of the most frequent cytogenetic abnormalities (CAs) in multiple myeloma (MM), and it is now widely acknowledged as a poor prognostic marker, included in all modern staging systems. Anti-CD38 monoclonal antibodies (moAbs), particularly daratumumab, have recently transformed MM treatment, significantly improving outcomes. However, data on +1q patients treated with daratumumab remain limited. Most pivotal trials did not report +1q-specific outcomes, and available data are restricted to a few post-hoc subgroup analyses or small sample real-world studies, often with conflicting results. To explore the prognostic impact of +1q in this setting, we conducted a single-center retrospective analysis on 174 MM patients treated with daratumumab-based therapies between May 2018 and December 2023. Cytogenetic data from FISH were available for 92 patients (52.9%); 38 had +1q (18 isolated, 20 with ≥1 high-risk CAs [HiRCAs]), 11 had HiRCAs other than +1q (non-1qHiRCAs). High-risk clinical features (extramedullary disease or circulating plasma cells) were observed in 20 cases. Most patients received daratumumab in first or second line (n=80 and n=73), predominantly as daratumumab, lenalidomide and dexamethasone (n=125). After a median follow-up of 30.7 months, patients with isolated +1q had significantly shorter PFS compared to patients without HiRCAs (mPFS 28.1 vs 66.8 months, p<0.001), but slightly longer than non-1qHiRCAs or +1q plus ≥1 HiRCAs patients (mPFS 24.8 and 20.3 months, respectively) (see Figure). Similar results were observed for time-to-next-treatment (TTNT) and OS, with isolated +1q patients significantly showing worse outcomes compared to patients without HiRCAs (mTTNT 35.6 vs 67.4 months, p=0.003; mOS NR vs NR, p=0.01), but better than non-1qHiRCAs patients (mTTNT 24.8 months; mOS 46.4 months) or +1q plus ≥1 HiRCAs patients (mTTNT 24.6 months, mOS 46.6 months). Multivariate analysis confirmed the independent adverse role of isolated +1q for PFS (HR 4.56, p=0.004) and TTNT (HR 3.64, p=0.017), with only a trend for OS (HR 2.62, p=0.151), whereas the worst effect was seen in patients with +1q plus ≥1 HiRCAs (PFS: HR 8.36, p<0.001; TTNT: HR 6.37, p<0.001; OS: HR 6.18, p=0.003). In conclusion, our findings highlight the role of +1q as an independent marker of poor prognosis in daratumumab-treated MM, even when not associated with other HiRCAs.