Gilteritinib Following AlloHCT Shows No Improvement in Health-Related Quality of Life Among Patients With FLT3-ITD AML

Phase 3 Results from the MORPHO Trial

According to phase 3 data from the MORPHO trial, gilteritinib maintenance therapy after allogeneic hematopoietic cell transplantation (alloHCT) in FLT3-ITD acute myeloid leukemia (AML) was not associated with any difference in health-related quality of life (HRQOL) when compared with a placebo.

“Several studies investigated the use of FLT3 inhibitors as maintenance therapy after HCT; however, their benefit remained unclear, particularly given risks of toxicity and poor tolerance,” stated lead study author Betty Hamilton, MD, Cleveland Clinic, Cleveland, Ohio, and coauthors.

Eligible participants included adult patients with a diagnosis of FLT3-ITD mutant AML in first complete remission (CR1) suitable to undergo allogeneic HCT from any donor and graft source, with any conditioning regimen and graft-versus-host disease prophylaxis. Between days 30 and 90 after HCT, participants were randomized to gilteritinib or placebo for 24 months; 356 patients were randomized, 178 to placebo and 178 to gilteritinib.

Investigators measured HRQOL with the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. The primary end point of the study was relapse-free survival (RFS) as assessed by a blinded end point review committee. Additionally, the primary analysis of this trial demonstrated no statistically significant difference in RFS; however, investigators noted that patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib.

Results demonstrated the HRQOL completion rate was acceptable (>70%) across all time points and measures. Furthermore, there were no recorded differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both treatment arms. Gilteritinib maintenance after allogeneic HCT also demonstrated a relapse-free survival (RFS) benefit among patients with AML in CR1 with detectable peri-HCT FLT3-ITD measurable residual disease (MRD).

Researchers noted despite higher treatment-emergent adverse effects with gilteritinib, patient response to the question of being “bothered by side effects of treatment” did not differ between cohorts. Additionally, a subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms, and HRQOL in both arms continued to improve over the 24-month period of post-HCT maintenance regardless of treatment.

“For patients with FLT3-ITD⁺ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effect,” concluded Dr Hamilton and colleagues.

Source:

Hamilton B, Pandya B, Ivanescu C, et al. Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+ acute myeloid leukemia. Blood Adv. Published online September 27, 2024. doi: doi.org/10.1182/bloodadvances.2024013746