C065 | CYTOGENETIC FEATURES AND THEIR IMPLICATIONS IN CLINICAL PRACTICE: A REAL-WORLD ANALYSIS OF A LARGE COHORT OF MULTIPLE MYELOMA PATIENTS

Background. Prognostic systems of Multiple Myeloma (MM) have undergone several revisions over the years, but cytogenetics by FISH remain the main prognostic factor. The aim of this study was to analyse cytogenetics and its implications in a large real-world (RW) cohort of MM patients (pts). Patients and Methods. Data came from 12 Italian hematology centers. Del(17p), del(p53), t(4;14), t(14;16), t(14;20), ampl(1q), del(1p), hypodiploidy, and their combinations (double hit: DH) were considered as high risk (HR) feature. Pts without FISH data (missing: M) were analysed separately. Results. We evaluated 1.026 MM pts treated from 2019 to 2023 (mF-up: 42 months). Of these, 501 were transplant eligible (TE) and 525 were not (NTE). FISH was evaluable in 643 pts (63%; 75% TE, 53% NTE), but not in 383 pts (37%). Out of 643 evaluable, 184 (29%) were classified as HR, 452 (70%) as standard risk (SR), and 7 (1%) as DH. In TE mPFS was 31.5, 62, and 60 months for HR, SR, and M, respectively (p<0.001). In NTE, it was 23, 36, and 30 months in the same 3 groups (p=0.020), respectively. Overall, 51 pts with 1q-1p alterations (ch1alt) had a mPFS of 39 months, those with chromosome 14, 17, p53 alterations and DH (HHR) had 30 months, while those with normal FISH, tris1q, t(11;14), and del13 (LR) had 62 months mPFS (p< 0.001; M: 60 months). Regarding therapeutic implications, pts treated with anti-CD38 combinations showed a significantly longer mPFS in both TE (NR vs 51.5 months; p=0.030) and NTE (23 vs 58 months; p<0.001) compared with who did not; however, for TE, the improvement was significant only for pts with ch1alt (30.5 vs NR; p=0.030), but not for those HHR (30 vs 31 months; p=0.987). In NTE, all risk groups benefited from anti-CD38. In TE group, double compared to single transplant did not improve mPFS either overall (HR: 36 vs 33 months; p=0.376; SR: 67 vs 64 months; p=0.874; M: 55 vs 60 months; p=0.885) or in specific HR subgroups (ch1alt: 30.5 vs NR; p=0.082, HHR: 35 vs 30 months; p=0.240). Conclusions. In real world, more than one third of MM pts do not have baseline FISH data. Current cytogenetic classification adequately discriminate risk groups in both TE and NTE pts. Anti-CD38 combination therapies improved the prognosis of all NTE pts, whereas this was not the case for HHR TE pts. Finally, in RW, double transplant did not confirm the advantage in PFS observed post-hoc in the EMN-02 and STAMINA trials, in any FISH risk groups, particularly in the HR groups.