P-224: Autologous transplantation is the strongest prognostic factor for overall survival in Multiple Myeloma patients with deletion 17p: 20-year Real-World experience of the Greek Myeloma Study Group.

Introduction: Deletion 17p (del17p) is a strong negative prognostic factor for survival in Multiple Myeloma (MM), and it is included in both the revised international staging system (RISS) and its 2^nd revision (R2-ISS). Our aim was to compare characteristics and outcomes of MM patients with or without del17p, and to explore possible other adverse prognostic factors for overall survival (OS) in patients with del17p, in the real-world setting.

Methods: We analyzed 1337 MM patients (M/F: 665/672, median age: 66, range: 33-92, IgG: 786, IgA: 350, light chain: 177, IgD: 8, non-secretory: 14, IgM: 2) who were diagnosed from 2003-2023, and included in the Greek Myeloma Study Group registry. Of those, 129 (9.6%) patients had del17p (median age: 65, range: 38-85; M/F: 67/62); 74/129 (57.4%) had del17p as a single abnormality (del17p-s), whereas 55 (42.6%) had del17p plus ≥1 other high-risk abnormality (del17p-plus).

Results: Age, eGFR, calcium, albumin, platelet counts, and bone marrow infiltration did not differ between del17p vs others (control group); LDH and β2-microglobulin were higher, while hemoglobin was lower in del17p patients (p< 0.05). Expectedly, R-ISS3 and R2-ISS4 were more common in patients with del 17p (31 vs 9% and 41% vs 26%, respectively; p< 0.001).

All patients were treated with novel anti-myeloma combinations; 487 (36.5%) received lenalidomide-based triplets (LBT i.e. lenalidomide-proteasome inhibitor-dexamethasone) or daratumumab-based regimens (DBR). Regarding del17p patients, 41/129 (32%) received LBT/DBR and 40 (31%) underwent autologous transplantation (ASCT) upfront; induction therapy did not differ between groups. After a median follow up of 57 months (95% CI: 53-61), 80/129 (62.0%) patients with del17p vs 479/1208 (39.6%) of controls deceased (p< 0.001). Median PFS and OS of patients with del17p vs others was 19 (95% CI: 15-23) vs 34 months (95% CI: 31-37), and 36.8 (95% CI: 26-47.6) vs 83 months (95% CI: 75-91), respectively (p< 0.001). PFS and OS did not differ between del17p-s vs del17p-plus patients. In the multivariate analysis for the whole population del17p, eGFR< 40mL/min/1.73m², R2-ISS, LBT/DBR induction and ASCT were significant prognosticators for OS. High-risk abnormalities other than del17p had no impact on OS. In multivariate analysis for the del17p cohort, ASCT was the only independent prognostic factor for OS (p< 0.001; HzR: 0.26 95% CI: 0.18-0.40). Median OS for patients who underwent ASCT vs others was 52.3 (95% CI: 25.9-78.7) vs 30 months (95% CI: 24.6-35.3), respectively (p=0.003).

Conclusions: We conclude that, in the real-world setting, del17p remains an independent prognostic factor for OS, surpassing the predictive value of other high-risk abnormalities. For patients with del17p, neither baseline prognostic markers/staging systems or current upfront regimens predicted for OS; ASCT remains a strong prognosticator underscoring its established therapeutic value in this high-risk population.