ASH 2018: Azacitidine With Nivolumab Plus Ipilimumab vs Azacitidine Plus Nivolumab in Relapsed or Refractory AML
A triplet therapy combining two immune checkpoint inhibitors with the standard of care azacitidine has shown promising results for treatment of relapsed or refractory acute myeloid leukemia (AML), according to the findings of a phase II study conducted at The University of Texas MD Anderson Cancer Center. The results from the study, led by Naval Daver, MD, Associate Professor of Leukemia at MD Anderson, were presented at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 616).
Study Details
The study compared two patient cohorts—the first included 70 patients who received azacitidine plus nivolumab. The second cohort with 20 patients was given a triple therapy employing the same two drugs with ipilimumab. Cohort 1 is now closed, whereas cohort 2 continues to enroll patients. Patients were eligible for cohort 1 if they had relapsed or refractory AML disease, an Eastern Cooperative Oncology Group performance status ≤ 2, and adequate organ function. Cohort 2 had the same eligibility criteria as cohort 1, except that enrollment was restricted to patients with salvage 1 and 2 AML.
Key Results
The triplet therapy showed activity, with a complete response rate of 43% and a projected 1-year overall survival of 58%. The azacitidine plus nivolumab cohort reported a complete response rate of 22%, with a projected 1-year overall survival of 40%. Responses in both cohorts included best response within 3 months of therapy initiation.
Adverse side effects were reported in 11% of the azacitidine plus nivolumab group, with the most common events being pneumonitis and colitis. The triplet therapy cohort reported grade 3 or 4 immune-related adverse events in 35% of patients, including pneumonitis, skin rash, pituitary hormone and liver enzyme irregularities, and colitis.
“The response rate and survival in patients with relapsed AML treated with azacitidine with both nivolumab and ipilimumab appears encouraging and potentially superior to azacitidine with nivolumab in a small cohort of patients,” said Dr. Daver in a statement. “However, we need to study more patients with longer follow-up to make firm conclusions. Immune-related toxicities are more common and may be more severe with this double checkpoint approach, and awareness and close monitoring, therapy interruption, and aggressive treatment of immune toxicities [are] critical if such approaches are to be successful.”
“The current triple therapy cohort will enroll up to 30 patients, and after that we plan to open a new cohort that will evaluate a higher dose of ipilimumab and a lower dose of nivolumab in 30 patients,” said Dr. Daver. “Once we analyze both cohorts and select the appropriate dosing approach, we hope to evaluate this approach in a larger multicenter study.”
Disclosure: See the study authors’ full disclosures at ash.confex.com.
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