Real World Outcomes in Acute Myeloid Leukemia Patients Following Post Hematopoietic Stem-Cell Transplantation Maintenance Treatment with Midostaurin or Sorafenib: A US Retrospective Cohort Study

INTRODUCTION: Disease relapse remains the most common reason for transplant failure and high mortality in patients undergoing hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML). As many as 30-40% of AML patients will relapse following HSCT, and the prognosis following relapse is poor with a 3-year survival rate of 20-30%. Post-transplant maintenance therapy aims to reduce this risk, and epigenetic modifiers, antibody-drug conjugates, and tyrosine kinase inhibitors (TKIs) represent possible maintenance options. To date, there is limited understanding of the clinical and economic burden of TKIs used for post-HSCT maintenance in patients with AML, and a lack of real-world evidence of tolerability, treatment persistence, relapse-free survival, and rates of key clinical events. This real-world study aimed to examine these outcomes in patients newly diagnosed with AML who received post-HSCT maintenance treatment with the TKIs midostaurin or sorafenib.

METHODS: This was a retrospective cohort study using the Inovalon® Insights Payer-Sourced ("Closed") dataset, one of the largest primary-sourced, longitudinal claims datasets in the U.S. The study sample included adult (≥18 years) AML patients who were newly diagnosed between 01 January 2016 and 30 June 2021 and received at least one HSCT after the first observed AML diagnosis, and maintenance treatment with midostaurin or sorafenib within the first 100 days following the first HSCT. Patients were followed-up from the index date (initiation date of the maintenance) to the earliest of treatment discontinuation, relapse, or end of patient eligibility / data availability. Primary outcomes assessed in this study included treatment duration, treatment gaps, key clinical events, relapse-free survival, and AML-related healthcare resource utilization.

RESULTS: In total, 77 patients were included in the study (58% male; mean age: 50 years; mean Charlson comorbidity score: 3.9) with 35 patients receiving post-HSCT maintenance treatment with midostaurin and 42 patients receiving sorafenib. The average treatment duration (including gaps <60 days) for all patients was 185 days, and for patients in the midostaurin and sorafenib cohorts was 160 and 206 days, respectively. In the total cohort only 16 patients (Kaplan-Meier survival probability 26%) continued treatment after 12 months, and this decreased further to only 3 patients (Kaplan-Meier survival probability 7%) after 24 months. Over half the total cohort, including 32 (76%) patients receiving sorafenib and 13 (37%) receiving midostaurin, had at least one treatment gap, with an average treatment gap duration of 44 and 21 days in the midostaurin and sorafenib cohorts, respectively. The prevalence of key clinical events in the patient groups were also assessed to identify the potential causes for the observed poor treatment adherence. Key events that occurred in over 40% of patients included graft versus host disease (69%), gastrointestinal symptoms (68%), anemia (64%), bleeding (56%), and hypertension (47%). Approximately 34% of patients had evidence of relapse. The mean time to relapse was 577 days in the total cohort and was 407 and 719 days in the midostaurin and sorafenib groups, respectively. With regards to AML-related healthcare resource use, the mean hospitalizations and outpatient services during year 1 in the total cohort were 1.0 and 27.7, respectively, with a mean hospitalization of 15 days.

CONCLUSIONS: Following HSCT in AML patients, maintaining remission and preventing relapse is an important outcome for patients. This study has demonstrated that maintenance treatment with midostaurin or sorafenib is associated with high treatment discontinuation and treatment gaps. In addition, a high incidence of key clinical events was reported with use of these agents. Consequently, there remains a substantial unmet need in the post-HSCT maintenance treatment of AML for therapies with a more favourable tolerability profile, that would enable more patients to continue treatment and prevent relapse.

Muffly:Pfizer: Consultancy; Kite: Consultancy, Research Funding; Medexus: Consultancy; CTI Biopharma: Consultancy; Astellas: Consultancy, Research Funding; Jasper: Research Funding; Adaptive: Honoraria, Research Funding; BMS: Research Funding; Adaptive: Honoraria; UpToDate: Consultancy, Honoraria; Novartis: Research Funding; Amgen: Consultancy. Young:Astellas: Current Employment. Xie:Astellas: Current Employment. Block:Astellas: Current Employment, Research Funding; ConcertAI: Other: Medical publication support. Touya:Astellas: Current Employment, Research Funding; ConcertAI: Other: Medical publication support. Pandya:ConcertAI: Other: Medical publication support; Astellas: Current Employment, Research Funding.