P897: EVALUATION OF THE PROGNOSTIC IMPACT OF SECOND LINE ANTI-MYELOMA TREATMENTS ON POST- PROGRESSION OUTCOMES IN THE REAL-WORLD SETTING: THE GREEK MYELOMA STUDY GROUP EXPERIENCE.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Treatment landscape of relapsed/refractory Multiple Myeloma (RRMM) has improved with the incorporation of monoclonal antibodies, novel proteasome inhibitors and pomalidomide. However, there is limited real-world data regarding the prognostic impact on post-progression survival of therapies applied in 2nd line. Aims: Our aim was to describe the treatment approaches in 2nd line and to evaluate post-progression survival parameters i.e., progression free survival (PFS), PFS2 and overall survival (OS) according to different therapies. Methods: We evaluated 725 RRMM patients (M/F: 349/376, median age: 66, range:38-88; IgG:416, IgA: 212, light chain: 71, IgD:9, non-secretory: 15, IgM:2) out of 1519 newly diagnosed MM patients with complete staging (ISS and R-ISS) and complete 1st and 2nd line data, diagnosed between 2003-2022, in Greek Myeloma Centers. A cox regression analysis was used to determine prognostic factors for post-progression OS; post-progression PFS and OS were plotted with Kaplan-Meier; p<0.05 was considered as statistically significant. Results: ISS stage was 1, 2 and 3 in 192, 345 and 188 patients, respectively; Per R-ISS, 161 patients were classified in stage I, 472 in stage II, and 92 in stage III; data of second revision of ISS (R2-ISS) was available in 75%; 96 patients were classified in low (I), 168 in low-intermediate (II), 235 in intermediate-high (III) and 42 in high risk (IV) R2-ISS. Induction therapy included conventional chemotherapy or thalidomide-based regimens (CT/TBR; n=211), bortezomib-based triplets (BBR; n=321), lenalidomide-dexamethasone (Ld; n=90), lenalidomide-based triplets (LBT; n=85), daratumumab-based regimens (DBR; n=18); 190/725 patients underwent upfront autologous transplantation (ASCT). Second line therapies were distributed as follows: CT/TBR: 106, BBR: 173, Ld: 204, LBT: 87, DBR: 115, pomalidomide-based regimens (PBR): 40; Patients treated with DBR or PBR were more often Lenalidomide exposed/refractory compared to others (55% and 62% vs. 17% for all others; p<0.001). After a median follow up of 63 months (95% CI: 56-69) median post-progression PFS for patients treated with CT/TBR, BBR, Ld, LBT, DBR and PBR in 2nd line was 11, 9, 15, 14, 31 and 16 months and it was significantly longer for patients treated with DBR (p<0.05). Post-progression OS was 20, 23, 33, 40, 42 and 25 months, respectively (Figure), and it was significantly longer for patients treated with DBR compared to BBR, CT/TBR, PBR and Ld (p<0.05), however it did not differ compared with patients treated with LBT (p>0.05); PFS2 was 31, 33, 45, 54, 72 and 45 months respectively and it was significantly longer in patients treated DBR compared with others (p<0.05); Univariate cox regression analysis demonstrated that ISS, R-ISS, R2-ISS at diagnosis, ASCT, 2nd line LBT and DBR were significant predictors for post-progression OS (p<0.05); ASCT, R2-ISS and 2nd line treatment with DBR were independent predictors for post-progression OS in the multivariate analysis (HR for ASCT: 0.67; p=0.002, HR for R2-ISS: (I) vs. (IV): 0.33; (II) vs. (IV): 0.31; (III) vs. (IV): 0.50; p<0.001 and HR for DBR: 0.63; p=0.01). Induction therapies, including LBT, did not correlate with post-progression OS. Summary/Conclusion: In conclusion, these real-world data demonstrated that treatment with DBR in 2nd line induced a 37% reduction in the risk for progression or death and improved significantly post-progression survival parameters. First line therapies including LBT did not affect post-progression OS, suggesting that DBR, may mitigate the negative impact of lenalidomide refractoriness.Keywords: Multiple myeloma, Prognosis