Introduction

Olutasidenib, a mutated IDH1 (mIDH1) inhibitor, was approved by the FDA for the treatment of adult patients with R/R mIDH1 AML, based on a Phase 2, open-label, multicenter clinical trial in 147 adult patients with R/R mIDH1 AML. Here, we assess the treatment patterns and outcomes with real world use of olutasidenib in clinical practice.

Methods

This real-world study utilized Komodo Health's patient-level longitudinal insurance claims database. Patients were included if they had a) >1 paid claim for olutasidenib, b) >1 claim with a diagnosis for AML from January 2016 to March 2024, c) an index AML diagnosis claim prior to starting olutasidenib, d) a claim for an AML drug treatment prior to starting olutasidenib, e) >180 days of lookback period prior to AML diagnosis, and f) age >18 years. Kaplan-Meier (KM) survival analysis was conducted to analyze duration of olutasidenib treatment (DOT) and time to transfusion independence (TTI). For DOT, patients were censored if olutasidenib was the last treatment and the treatment ended <60 days from study end. TTI analysis was conducted in patients with a transfusion in the 8 weeks prior to start of olutasidenib. TI was assigned at the end of the first 8-week transfusion-free period after the start of olutasidenib. Those not attaining transfusion independence were censored at study end.

Results

The study included 47 patients diagnosed with AML. Median age at diagnosis was 71 years, and 55% were female.

75% patients started olutasidenib in 2023, and 23% in 2024. Most (37; 79%) received olutasidenib as monotherapy and 10 (21%) in combination with other agents. Over half received olutasidenib as their first (6%), second (28%) or third (28%) regimens, while 38% received olutasidenib as a fourth or later regimen (median=3). Most (78%) patients had prior treatment with venetoclax, mostly in combination with a hypomethylating agent or a targeted therapy. 10 (21%) patients had a prior stem cell transplant.

The median duration of olutasidenib treatment (DOT) was 4.5 months, similar to that in the registrational trial (median DOT 4.7 months). In patients who received prior venetoclax, the median DOT was 4.2 months (range: 1.0-8.1 months), which is similar to data reported from the venetoclax exposed subgroup in the clinical trial.

Nearly half (49%) of patients had prior ivosidenib exposure; such exposure did not appear to impact the DOT (median 4.1 months; range 1.0-8.1 months vs. for the overall cohort, median 4.5 months, range 1.0-8.1 months). At data cut off, 61% of patients with prior ivosidenib and 68% with prior venetoclax exposure were continuing treatment with olutasidenib.

Of the 19 patients who were TD at the start of olutasidenib, 11 (58%) achieved 8-week transfusion independence (TI); the median time to attain TI was 16 weeks. TD patients utilized a median of 19 transfusion units over a mean of 8 weeks prior to olutasidenib start, which decreased to a median of 13 units over a mean of 12 weeks during olutasidenib treatment and then increased to a median of 22 units over a mean of 6 weeks after stopping olutasidenib.

A limitation of this real-world study is the incomplete availability of data related to patient characteristics, response, and adverse events. While these missing data preclude the fuller picture provided by a clinical trial; real world data provide a window into clinical utilization of treatments in a broad range of patients.

Conclusion

This assessment of treatment patterns provides insight into how olutasidenib is used in the real world, the potential impact of sequential treatments, and clinically relevant outcomes including transfusion burden and independence. The median duration of olutasidenib treatment was comparable to that in the registrational clinical trial. A large percentage of olutasidenib use is in the post-venetoclax setting. While almost 40% of patients received olutasidenib as a fourth or later regimen in this study, results from the pivotal study showed a higher response rate for patients having received 1-2 prior therapies vs 3+, suggesting a case for treating earlier. Previous treatment with ivosidenib did not appear to adversely impact treatment duration with olutasidenib suggesting that olutasidenib has comparable clinical utility for patients with and without prior ivosidenib exposure.

Disclosures

Sheppard:Rigel Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Wang:Rigel Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Potluri:BMS: Consultancy; Pfizer: Consultancy; Janssen: Consultancy; Putnam Associates: Current Employment; AstraZeneca: Consultancy; Servier: Consultancy; Cytokinetics: Consultancy; Rigel Pharmaceuticals, Inc.: Consultancy. Papademetriou:Cytokinetics: Consultancy; Servier: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; BMS: Consultancy; Rigel Pharmaceuticals, Inc.: Consultancy; Cigna: Current equity holder in publicly-traded company; Putnam Associates: Current Employment.

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2024
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