|The following article features coverage from the American Society of Hematology 2021 meeting. Click here to read more of Hematology Advisor‘s conference coverage.|
A combination of pevonedistat plus azacitidine does not appear to improve outcomes compared with azacitidine alone among patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) with 20% to 30% marrow blasts, according to research presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
Higher-risk MDS/CMML and AML with 20% to 30% marrow blasts are generally treated with hypomethylating agent therapy, although the prognosis remains poor, particularly among older patients. There is, therefore, a need for improved treatment options in this patient population.
Pevonedistat, a selective inhibitor of NEDD8-activating enzyme, previously showed promise in combination with azacitidine among patients with higher-risk MDS and AML with 20% to 30% marrow blasts. For the randomized phase 3 PANTHER trial (ClinicalTrials.gov Identifier: NCT03268954), researchers compared the safety and efficacy of pevonedistat plus azacitidine with that of azacitidine alone among patients with MDS/CMML and AML with 20% to 30% marrow blasts.
Overall, 454 patients were randomly assigned to the experimental group (227 patients) or azacitidine only (227 patients); 324 patients had higher-risk MDS, while 27 had higher-risk CMML and 103 had AML. In the intention-to-treat population, in the experimental and single-therapy arms, 58% vs 63% of patients were male, respectively, 91% vs 86% were aged 65 years or older, and 89% vs 84% of patients had an Eastern Cooperative Oncology Group performance status of 0.
In the intention-to-treat population, the overall response rate was 28% in the experimental group vs 32% in the azacitidine-only group. The median event-free survival with pevonedistat plus azacitidine was 17.7 months compared with 15.7 months in the azacitidine-only group (P =.557); median overall survival was 20.3 months vs 16.8 months, respectively (P =.181).
Event-free survival and overall survival improvements were not, furthermore, noted in the high-risk MDS or AML with 20%-30% marrow blast cohorts.
The most common grade 3 or 4 adverse events in the experimental and control arms were anemia (33% and 34%, respectively), neutropenia (31% and 33%), and thrombocytopenia (30% and 30%).
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Hematology Advisor‘s coverage of the ASH 2021 meeting by visiting the conference page.
Sekeres MA, Girshova L, A Doronin VA, et al. Pevonedistat (PEV) + azacitidine (AZA) versus AZA alone as first-line treatment for patients with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML) with 20–30% marrow blasts: the randomized phase 3 PANTHER trial (NCT03268954). Presented at ASH 2021; December 11-14, 2021. Abstract 242.