ARGENTINEAN REAL WORLD EXPERIENCE ON MIDOSTAURIN PLUS INTENSIVE CHEMOTHERAPY VS INTENSIVE CHEMOTHERAPY TO TREAT FLT3 POSITIVE ACUTE MYELOID LEUKEMIA PATIENTS

NAVICKAS, ALICIA; GONZALEZ, JACQUELINE; RIVAS, MARÍA M; CLAVIJO, MANUELA; CARNELUTTO, NATALIA; FUNES, MARIA EUGENIA; MELA OSORIO, MARIA JOSE; MARIANO, ROMINA; RAPAN, LETICIA; MOIRANO, MARÍA M; REY, IRENE; CRANCO, SANTIAGO; GIUNTA, JUAN; RAMIREZ, ROXANA; CASTRO, MARÍA B; ENRICO, ALICIA; GIMENEZ CONCA, ALBERTO; BELLI, CAROLINA B

Viena

Congreso; 27th Congress of the European Hematology Association; 2022

European Haematology Association

Background: Midostaurin has been approved by EMA and FDA in combination with intensive chemotherapy (CMT) for FLT3 positive AML based on improved survival. In Argentine was included among therapy strategies in 2018. The realworld experience in day-to-day practice is limited.Aims: To examine the impact of introduction of midostaurin within the backbone to treat FLT3+ AML patients in an Argentinean cohort.Methods: This is a retrospective analysis of 120 FLT3+ AML patients intensively treated with or without midostaurin excluding APL- and CBF-AML, from the Argentine Society database of 1200 AML diagnosed between March-13/Dec-21 including 20 centers. Responses were evaluated according to the ELN 2017 criteria for intensive chemotherapy (CMT).Statistical analysis included Chi2/Fisher’s exact test, Kaplan-Meier survival analysis, censoring or not at HSCT, to last follow-up or death.Results: FLT3 variants were 103 (86%) ITD, 15 (13%) TKD and 2 (1%) ITD/TKD. Seventy-two patients received first line treatment with standard 7+3 CMT and 48 added midostaurin. Sex ratio M/F was 0.6 (47/73) with a median age of 50.7 years (15.1-76.4), being 25% >60 years old, 26% an ECOG>1, 17% a Charlson’s Index (CCI)>2, 95 (97%) intermediate MRC karyotypes (23 not available), 43 (43%) NPM1+ (21 not available). No differences were observed between both populations regarding basal characteristics.The median time to treatment initiation was 3 days, and with a median follow-up of 8.2 months, 84 (68%) died with an early mortality at 28 days of 9.6% (1/11 received midostaurin). Regarding responses on those treated with CMT 64% (n=46) obtained Complete Remission (CR), subsequently 37 pts (51%) received consolidation with high doses of CMT, 13 pts relapsed, and 26 received HSCT. Within the MDT cohort, 79% (n=38) achieved CR, 37 (77%) were consolidated, 7 pts relapsed, and 25 received HSCT.The inclusion of MDT to CMT improved the outcome of our patients. The overall survival censoring at HSCT was 7.0 vs 4.7 (95%CI 1.7-12.4 vs 3.1-6.4, p=0.002), not censoring 12.1 vs 7.7 (95%CI 0.4-23.8 vs 5.5-9.9, p=0.008). Among those who achieved CR, the OS was 24.8 vs 10.3 (95%CI 7.9-41.7 vs 6.7-13.9, p=0.046) and 11.9 vs 6.4 (95%CI 9.5-14.4 vs 5.4-7.4, p=0.015), without differences regarding relapse free survival, evaluated to last follow-up (median not reached,p=0.800). No statistical differences were observed regarding survival after HSCT (9.6 vs 10.3, p=0.773). In our media FLT3 inhibitors are not approved as maintenance therapy after HSCT.Summary/Conclusion: Our results in day-to-day practice confirm that midostaurin associated with CMT improved the outcome of FLT3 positive AML patients.