Efficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2)

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.736-736
• Main Authors: Stempel, Jessica M., Uy, Geoffrey L., Dinner, Shira N., Gojo, Ivana, Reed, Daniel, Roy, Rupali, Byrd, Kenneth P, Yerrabothala, Swaroopa, Lai, Catherine E., Doucette, Kimberley, Caldwell, Anne, Blaha, Ondrej, Podoltsev, Nikolai A., Mendez, Lourdes M, Bewersdorf, Jan Philipp, Kewan, Tariq, Wistuba, Ignacio, Alatrash, Gheath, Haymaker, Cara L, Streicher, Howard, Sharon, Elad, Little, Richard, Gore, Steven D., Radich, Jerald P., Wood, Brent L., Zeidan, Amer M., Shallis, Rory M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-210370

AMZ, RMS Contributed equally and serve as co-senior authors Background AZA + VEN is a standard of care treatment for pts with AML who are unfit for intensive chemotherapy. However, long-term survival remains limited. Addition of anti-PD-1 antibody to AZA+VEN may activate T-cells against blasts, induce higher rates of measurable residual disease (MRD)-negativity (neg), and improve outcomes. We report results of a randomized, phase II trial of AZA+VEN +/- PD-1 inhibition for pts with AML ineligible for intensive induction (NCI10334, NCT04284787). Methods BLAST AML-2 is an investigator-initiated, multi-center, CTEP-sponsored, open-label, randomized phase II trial. We randomized (1:1) pts aged ≥60 years with non-core binding factor, FLT3 wild-type, newly diagnosed AML who were ineligible for/declined intensive induction to receive AZA (75 mg/m2 IV/SQ x7 days [D], D1-7 or D5-2-2) + VEN (400 mg/d, D1-28) or AZA+VEN and pembrolizumab (PEM; 200 mg IV, D8 of cycle [C] 1, then every 3 weeks). VEN was adjusted at investigator discretion. The primary endpoint was complete remission (CR)/CR with incomplete count recovery (CRi) with MRD-neg assessed by centralized flow cytometric analysis at 0.1% threshold within the first 6 cycles. Disease and MRD status were evaluated after cycles 2, 4, 6, then every 3 months (mo). Multiplex immunofluorescence, whole exome sequencing, RNA/T-cell receptor sequencing, CyTOF, and Olink cytokine analyses are planned in collaboration with the Cancer Immune Monitoring and Analysis Centers (CIMACs). This protocol was IRB approved, all patients provided informed consent, and the trial was conducted according to the Declaration of Helsinki. Results During a planned safety run-in period, the first 6 pts who received PEM had no dose limiting toxicities. 60 pts were then randomized (31 to AZA+VEN, 29 to AZA+VEN+PEM) between 2/16/21-6/5/23. 2 pts in control arm withdrew consent prior to receiving study treatment and were not included in analysis. For this data cut, median follow up was 12.2 months. Median age was 73 (range: 62-82) years; 38 (66%) were male. The majority of pts were white (48, 83%), 5 (9%) were African-American. Most pts had intermediate cytogenetic risk (N=42, 72%) and ELN 2022 adverse risk (N=39, 67%). There were no significant differences in relevant baseline patient- or disease-specific characteristics. Both arms received a median of 3 cycles of AZA+VEN (interquartile range: 2-7). 2 pts in each arm did not complete C1 (withdrew