PF632 EARLY SALVAGE TREATMENT WITH SECOND‐GENERATION NOVEL AGENTS AT BIOCHEMICAL RELAPSE PROLONGS OVERALL SURVIVAL: A REAL‐WORLD SINGLE CENTER EXPERIENCE
Authors: A. Romano, V. Del Fabro, V. Leotta, U. Markovic, E. Martino, M. Parisi, V. Calafiore, G. Sapienza, A. Orofino, F. Di Raimondo, C. Conticello
Journal: HemaSphere (2019)

Background: Despite therapeutic advances, multiple myeloma (MM) remains largely incurable and patients invariable develop relapsed or refractory (R/R) disease. Relapse can be characterized according to disease aggressiveness and the presence of clinical symptoms. Aggressive relapse can occur at biochemical level, due to rapid and relevant increase of monoclonal component or LDH, or at clinical level, defined by the presence of extramedullary disease, acute renal injury or progression to secondary plasma cell leukemia. Aims: To identify the clinical outcome upon treatment with second generation novel agents (pomalidomide, carfilzomib) and monoclonal antibodies (elotuzumab, daratumumab), we collected evidence of the best timing in providing early salvage treatment to RRMM. Methods: According to regulatory Italian laws, patients (N = 128) received one of the following regimens: KRd (N = 42, group A), Poma‐Dex (N = 77, group B), Daratumumab (in monotherapy, N = 12; associated to bortezomib, N = 18, associated to lenalidomide, N = 3), or Elotuzumab associated to lenalidomide (N = 12, group C). Among second generation novel agents‐treated patients (N = 128), 100 patients were exposed only to pomalidomide (N = 57), Daratumumab (N = 4), Daratumumab plus bortezomib and desamethasone (N = 6), Daratumumab plus lenalidomide and desamethasone (N = 1), Elotuzumab plus lenalidomide and desamethasone (N = 8), Carfilzomib plus lenalidomide and desamethasone (N = 24); 20 patients were exposed to two second generation of novel agents (pomalidomide and KRd N = 4, pomalidomide and Daratumumab N = 4, pomalidomide and EloRd N = 2, pomalidomide and DaratumumabVD N = 3, KRd and Daratumumab N = 1, KRd and DaratumumabVD N = 5, EloRd and DaratumumabVD N = 1), 7 patients to three combination (pomalidomide and KRd and Daratumumab N = 4, pomalidomide and KRd and Daratumumab VD N = 2, KRd and Dararumumab and DratumumabVD N = 1), 1 patient to pomalidomide, daratumumab, EloRd and KRd. Results: From July 2014 to January 2019 we evaluated 166 R/R MM treatments of 128 patients (58% males, median age 62 years, range 45–78), relapsed (N = 76, 59%) and relapsed/refractory (N = 52, 41%) patients, treated at biochemical (N = 87, 68%) or clinical relapse (N = 41, 32%). Median number of previous lines was 3 (1–13), including autologous stem cell transplantation (ASCT) in half of cases (N = 64, 50%). FISH was repeated before to start the second‐generation drugs, and it was available in 53 cases: 11 carried on high‐risk (del 17p, t4;14 or t14;16) and 42 standard‐risk cytogenetics, without any additional marker compared to the matched sample at diagnosis. For the whole cohort, longer overall survival (OS) was associated to treatment at biochemical relapse (27.8 vs 15.2 months, p = 0.0005), in relapsed patients instead of relapsed and refractory (34.1 vs 19.3 months, p = 0.0004), who received less than 3 lines of therapy (33.6 vs 19.1 months, p = 0.002), carrying standard‐risk cytogenetics (20.4 vs 11.2 months, p‐value not significant for low numbers in two groups) without any significant difference due to previous ASCT or the type of second‐generation treatment chosen. In multivariable analysis only type of relapse (biochemical versus clinical) and refractory status were independent predictors of overall survival ( p &lt; 0.0001). Summary/Conclusion: In our community setting data, heavily pretreated patients achieved improvement of outcome obtaining a median OS &gt;12 months, using second generation novel agents. Earlier treatment at biochemical asymptomatic relapse is associated with longer OS, suggesting that the most efficacious combinations should be anticipated within the first lines to prolong OS.