Abstract
Mutations in the isocitrate dehydrogenase 1 (mIDH1) gene occur in approximately 7%–14% of patients with acute myeloid leukemia (AML). Olutasidenib is a selective, potent, oral mIDH1 inhibitor approved for treatment of relapsed/refractory (R/R) mIDH1 AML. In the pivotal phase 2 trial (NCT02719574), olutasidenib demonstrated a complete remission/complete remission with partial hematologic recovery (CR/CRh) rate of 35%, with a median response duration of 25.3 months.
To evaluate the efficacy and safety of olutasidenib in patients with R/R AML, stratified by number of prior treatment regimens.
In this post hoc analysis of the pivotal phase 2 study, adult patients received olutasidenib 150 mg BID. Efficacy endpoints for the analysis included CR/CRh, overall response rate (ORR), duration of response (DOR), and overall survival (OS), based on when patients received olutasidenib: after 1–2 vs ≥3 prior regimens. All participants gave informed consent.
The efficacy population included 147 patients (1–2 prior regimens: n = 93; ≥3 prior regimens: n = 54). Median age was 72 years in the 1–2 prior regimens group and 66.5 years in the ≥3 prior regimens group. Prior treatment with hypomethylating agents was reported in 43% and 33%, respectively; prior venetoclax use in 11% and 4%, respectively. All 17 patients with prior hematopoietic stem cell transplantation were in the ≥3 prior regimens group (31%). Patients treated after 1–2 prior regimens had higher ORR (54% vs 39%) and CR/CRh rates (41% vs 24%), a greater proportion achieving CR (38% vs 22%), and longer median OS (13.0 vs 8.9 months) compared with patients treated after ≥3 prior regimens. All patients experienced ≥1 treatment-emergent adverse events (TEAEs). Serious TEAEs occurred in 73% (68/93) and 78% (42/54) for 1–2 and ≥3 prior regimens, respectively; grade ≥3 TEAEs occurred in 89% (83/93) and 91% (49/54), respectively. The most common TEAEs were nausea, decreased red blood cell count, and fatigue. No new safety signals were identified.
Patients who received olutasidenib earlier in the treatment course (after 1–2 prior regimens) had better clinical outcomes than patients treated later (after ≥3 prior regimens), supporting the potential benefit of earlier use of olutasidenib in the R/R setting.
Forma Therapeutics, Inc.
Rigel Pharmaceuticals, Inc.