Reference: August 2026 | Issue 8 | Vol 12 | Page 36
Triplet therapy with azacitidine (AZA), venetoclax (VEN), and the FLT3 inhibitor gilteritinib (GILT) induces a high response rate in FLT3-mutated acute myeloid leukaemia (AML) but is frequently complicated by prolonged myelosuppression and infectious complications which impact treatment duration. In relapse/refractory (R/R) AML, the median number of cycles is approximately two. A retrospective study performed by a team at Sweden’s Karolinska Institutet compared three GILT-based triplet regimens to identify an optimal scheduling strategy with respect to tolerability and clinical outcomes.
Twenty-nine patients with FLT3-mutated AML treated with AZA, VEN, and GILT were recruited from five Swedish centres. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS) and time to neutrophil and platelet recovery.
Patients received one of three regimens: concomitant triplet therapy from day 1 (Group 1); AZA and VEN followed by concomitant VEN and GILT (Group 2); or overlapping AZA and VEN followed by GILT monotherapy (Group 3).
Patients in Group 1 (n=13) were younger, with a median age of 49 years, compared with 75 and 76 years in Group 2 (n=9) and 3 (n=7), respectively. Patients in Group 1 were generally fitter, eligible for more myelosuppressive treatment, and often continued to haematopoietic stem cell transplantation (HSCT). In contrast, the regimens used in Group 2 and 3 were selected for more frail patients, considered unfit for fully concomitant GILT triplet (Group 1) due to anticipated myelosuppression.
At 18 months, OS for the entire cohort was 78.6 per cent, with median OS not reached after more than five years of follow-up. High response rates were observed across all schedules, with a modified composite complete remission (mCRc) rate of 94.7 per cent. Median OS was not reached in Groups 1 and 2 after three years, whereas Group 3 had a median OS of 18 months – however, the difference did not reach statistical significance.
Median EFS was 40.5 months in Group 1 and was not reached at five years in Group 2, compared with 11.5 months in Group 3 (P=0.04 and P=0.05, respectively).
Myelosuppression differed significantly between schedules. The median time to absolute neutrophil count (ANC) recovery (>0.5×109/L) after cycle 1 was 58 days in Group 1, compared to 39 days in Group 2 (P=0.006) and 38 days in Group 3 (P=0.006). The estimated median time to platelet (PLT) recovery (>50×109/L) was 105 days for Group 1, with only 11 per cent of patients regenerating before day 60. In contrast, the median time to PLT recovery in Group 2 and 3 was 43 and 36 days, respectively.
The results suggest that regimens that limit concomitant exposure to no more than two agents significantly reduce myelosuppression and infectious complications compared with fully concomitant triplet therapy. Schedules without triple-drug overlap enabled sustained treatment administration through reduced toxicity and were associated with durable disease control, including in patients ineligible for allogeneic HSCT.
Reference
Arvidsson Kvissberg M, et al. Patient tailored azacitidine, venetoclax, and gilteritinib triplet therapy achieves durable disease control and improves tolerability in FLT3-mutated AML. Abstract PS1651. European Hematology Association Congress 2026. June 11-14, 2026. Stockholm, Sweden.
