Revumenib represents a ‘significant breakthrough’ for treatment of acute leukemia
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Key takeaways:
- Most patients in the study had an objective response to treatment with revumenib.
- Few patients discontinued therapy with revumenib due to treatment-associated adverse events.
Revumenib proved safe and effective among pediatric and adult patients with relapsed or refractory KMT2Ar acute myeloid leukemia and acute lymphoid leukemia, according to study results presented at ASH Annual Meeting and Exhibition.
The findings also showed low rates of treatment discontinuation and dose reduction from adverse events associated with revumenib (SNDX-5613, Syndax Pharmaceuticals).
“Revumenib positive response rates and potential for successful transplants represent a significant breakthrough for patients with leukemia who have limited treatment options,” Ibrahim T. Aldoss, MD, hematologist-oncologist and associate professor in the division of leukemia in the department of hematology and hematopoietic cell transplantation at City of Hope, told Healio. “We are committed to advancing our research and development capabilities to better support this patient community.”
Background
There is a critical need for research and effective treatment options for patients with relapsed or treatment-resistant KMT2Ar acute myeloid leukemia and acute lymphoid leukemia, according to Aldoss.
“Fewer than 10% of these patients respond to chemotherapy, which is needed to receive a bone marrow transplant — the only cure for these types of leukemia — and therefore face a devastating survival rate of approximately 3 months,” he said.
Previous research has shown revumenib, an investigational small-molecule inhibitor of menin-KMT2A, demonstrated preliminary safety and efficacy, and the FDA granted a breakthrough therapy designation to the agent for treatment of adults and children with relapsed or refractory acute leukemias that harbored a KMT2A rearrangement.
For the phase 2 AUGMENT-101 trial, researchers enrolled 94 patients (median age, 37 years) with KMT2A acute myeloid leukemia (AML), acute lymphoid leukemia or mixed phenotype acute leukemia.
Patients received 163 mg revumenib (95 mg/m2 if more than 40 kg) every 12 hours combined with a strong cytochrome P450 3A4 oral inhibitor for 28-day cycles. Treatment continued until unacceptable toxicity or lack of at least morphologic leukemia-free state after four treatment cycles.
Primary study objectives included safety and tolerability of revumenib and complete remission, as well as complete remission with partial hematologic recovery rate. Secondary endpoints included composite complete remission rate and overall response rate.
Researchers additionally conducted a planned interim analysis of pooled adult and pediatric patients with KMT2Ar acute leukemia.
Findings
Results showed 22.8% (95% CI, 12.7-35.8) of adult and pediatric patients achieved complete remission or complete remission with partial hematologic recovery with revumenib.
Researchers additionally observed an overall response rate of 63% (95% CI, 49.3-75.6), according to results of the pooled interim analysis.
Of note, only 6.4% of patients discontinued therapy due to treatment-associated adverse events, and no discontinuations occurred due to differentiation syndrome or QTc prolongation, researchers noted.
“These findings indicate a positive therapeutic effect among the majority of trial participants, as well as a positive safety profile and deep remission,” Aldoss said. “Thirty-nine percent of patients with [objective response] were able to receive a bone marrow or stem cell transplant, which is a critical factor in curing these leukemia types.”
Implications
The positive response rates, safety profile and potential for successful bone marrow or stem cell transplant suggest that revumenib could offer a promising and urgently needed targeted treatment option for this patient population, Aldoss told Healio.
“If approved by the FDA, revumenib would be the first therapy to target the menin-KMT2A interaction,” he said. “This could provide a novel approach to addressing the genetic defect underlying these leukemia types. The next step is submitting a new drug application to the FDA for revumenib. Looking further ahead, future research is needed to focus on broader applications and long-term efficacy. Continued innovation is needed to address medical gaps in leukemia treatment.”