Healthcare resource utilization in patients receiving quizartinib or placebo in combination with chemotherapy for newly diagnosed, FLT3-ITD+ acute myeloid leukemia: An analysis from the QuANTUM-first trial

Abstract Introduction: The global, randomized, placebo (Pbo)-controlled, phase 3 QuANTUM-First trial (NCT02668653) evaluated quizartinib (Quiz), a novel oral FLT3 inhibitor, in combination with induction and consolidation chemotherapy, and as maintenance monotherapy in patients (pts) with newly diagnosed FLT3-ITD+ acute myeloid leukemia (AML). Quiz showed improved median (95% CI) overall survival of 31.9 months (mo; 21.0–not estimable) vs 15.1 mo (13.2–26.2) for Pbo (HR 0.78 0.62–0.98; P=0.032), leading to its approval for newly diagnosed FLT3-ITD+ AML. Intensive chemotherapy for AML incurs substantial healthcare resource utilization (HRU) due to prolonged hospitalization, requiring close monitoring and regular transfusions to manage myelosuppression. FLT3 inhibitors, including Quiz, are associated with myelosuppression as a class effect, predominantly neutropenia, thrombocytopenia, and anemia. We assessed HRU, including hospitalizations and transfusions, to evaluate the impact of myelosuppression in QuANTUM-First. Methods:HRU was analyzed by treatment (Tx) arm and study phase (data cutoff August 13, 2021): induction chemotherapy (≤2 cycles), consolidation chemotherapy (≤4 cycles), and monotherapy maintenance (≤36 28-day d cycles). Hematopoietic stem cell transplantation (HSCT; no study drug administered) was at the investigators' discretion. For each pt, total length of hospitalization, length in each phase, and proportion of days hospitalized in the maintenance phase were calculated. Descriptive statistics are provided for blood transfusions (whole blood, packed red blood cells, plasma, platelets) relative to days in each phase. Results:HRU data were available for 533 (99%) of 539 randomized pts (Quiz n=265/268; Pbo n=268/271). Pts who received 1 cycle of induction were hospitalized for a mean (95% CI) of 35.3 d (33.8–36.8) in Quiz (n=212) vs 34.2 d (32.5–36.0) in Pbo (n=212). Across the induction phase, inclusive of reinduction, pts were hospitalized for a mean (95% CI) of 42.8 d (40.4–45.2) and 40.5 d (38.3–42.8), respectively. In the consolidation phase (Quiz n=169; Pbo n=171), mean (95% CI) duration of hospitalization was 29.3 d (26.1–32.4) in Quiz vs 22.7 d (19.8–25.6) in Pbo, for pts who received 1 cycle; 49.2 d (43.4–55.0) vs 48.2 d (41.9–54.6) for pts with 2 cycles; 80.5 d (71.5–89.5) vs 71.7 d (64.8–78.6) for pts with 3 cycles; and 81.9 d (64.6–99.3) vs 94.7 d (81.5–107.9) for pts with 4 cycles. For HSCT pts (Quiz n=102; Pbo n=91), mean (95% CI) duration of hospitalization during HSCT was 31.4 d (26.1–36.6) with Quiz vs 29.3 d (23.4–35.1) with Pbo. In the maintenance phase (Quiz n=116; Pbo n=92), mean Tx duration overall was 17.7 cycles of Quiz vs 18.1 cycles of Pbo. The mean (95% CI) proportion of d hospitalized was low: 4.9% (2.4–7.5) with Quiz vs 6.2% (3.0–9.4) with Pbo. For HSCT pts (Quiz n=74; Pbo n=51), mean Tx duration was 18.5 cycles with Quiz vs 20.3 with Pbo, and mean (95% CI) proportion of d hospitalized was 5.2% (2.3–8.1) vs 5.9% (1.3–10.6), respectively; among non-HSCT pts (Quiz n=42; Pbo=41), mean Tx duration was 16.4 cycles with Quiz vs 15.3 cycles with Pbo, and 4.5% (0.0–9.4) vs 6.6% (2.2–10.9) d hospitalized, respectively. Transfusion requirements, a surrogate for Tx-related myelosuppression, were similar between arms. During induction, pts in the Quiz and Pbo arms received 313 and 302 transfusions per 1000 pt-d, respectively; this declined during consolidation (119 vs 113 per 1000 pt-d) and was lowest during maintenance (4 vs 3 per 1000 pt-d). During HSCT, pts in the Quiz and Pbo arms received 12 and 7 transfusions per 1000 pt-d, respectively. Conclusions:HRU was generally comparable between arms across all phases of therapy, predominantly due to the intensity of the backbone chemotherapy used in induction and consolidation. Notably, in the maintenance phase, Quiz monotherapy was associated with a numerically lower mean proportion of days hospitalized vs Pbo, regardless of HSCT status. These outcomes indicate that the addition of Quiz, and its class effect of myelosuppression, did not result in a clinically meaningful increase in HRU in terms of days hospitalized or transfusion burden, supporting the tolerability of Quiz in combination with induction and consolidation, and especially during maintenance monotherapy. Collectively, these findings and the significant survival advantages seen with Quiz further support the clinical feasibility of this regimen for newly diagnosed FLT3-ITD+ AML.