|The following article features coverage from the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO). Click here to read more of Hematology Advisor‘s conference coverage.|
In patients with higher-risk myelodysplastic syndromes (MDS), the combination of treatment with pevonedistat and azacitidine (AZA) was recently evaluated in the P-2001 study. Study results were presented at the Society of Hematologic Oncology (SOHO) 2021 Annual Meeting by Justin Watts, MD, of Sylvester Comprehensive Cancer Center at the University of Miami in Miami, FL, and colleagues.
This phase 2 study (ClinicalTrials.gov Identifier: NCT02610777) enrolled patients with higher-risk MDS, chronic myelomonocytic leukemia, and acute myeloid leukemia with 20% to 30% marrow blasts who had not had prior treatment with a hypomethylating agent. Patients were randomized 1:1 to receive either pevonedistat with AZA or AZA alone. The study originally had a primary endpoint of event-free survival (EFS), but the endpoint was changed to overall survival (OS).
In their poster, Dr Watts and colleagues focused on outcomes for the subset of patients with higher-risk MDS, which was defined as an intermediate or higher risk according to Revised International Prognostic Scoring System (IPSS-R) criteria. Some analyses used the Cleveland Clinic model formula for determining risk.
Among patients with higher-risk MDS, 32 were in the group given pevonedistat with AZA, and 35 were in the AZA-only group. Based on IPSS-R risk criteria, patients with higher-risk MDS had a median OS of 23.9 months with pevonedistat plus AZA and a median OS of 19.1 months with AZA only (hazard ratio [HR], 0.701 [95% CI, 0.386-1.273]; P =.240). The median EFS with pevonedistat plus AZA was 20.2 months, compared with 14.8 months with AZA only (HR, 0.539 [95% CI, 0.292-0.995]; P =.045).
With patients considered to have high-risk MDS according to the Cleveland Clinic model, the median OS was 24.2 months with pevonedistat plus AZA, and it was 14.2 months with AZA alone (HR, 0.447 [95% CI, 0.190-1.050]; P =.056). In these patients the median EFS was 20.2 months with pevonedistat plus AZA, compared with 11.7 months for AZA alone (HR, 0.388 [95% CI, 0.166-0.902]; P =.023).
In response-evaluable patients with higher-risk MDS, the overall response rates were 79% with pevonedistat plus AZA and 57% with AZA only (P =.065). The complete response rate was 52% with pevonedistat plus AZA, compared with 27% for AZA only (P =.050).
Median durations of response were 34.6 months (95% CI, 11.53-34.60) with pevonedistat plus AZA and 13.1 months (95% CI, 12.02-not evaluable) with AZA only. The median duration of transfusion independence appeared longer with pevonedistat plus AZA (23.3 months), compared with AZA only (11.6 months; HR, 0.11 [95% CI, 0.01-0.94]; P =.016).
Patients in the combination arm received a higher mean number of cycles of therapy than patients on AZA alone did (16.3 versus 10.7 cycles, respectively). Exposure-adjusted rates of adverse events were reported to be lower with the combination and without added myelosuppression.
The study investigators considered their findings to suggest encouraging efficacy with the combination of pevonedistat plus AZA in this population. They also indicated this combination seemed favored for EFS and OS in patients categorized as high risk based on Cleveland Clinic model criteria.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
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Watts J, Sekeres MA, Radinoff A, et al. Pevonedistat plus azacitidine vs. azacitidine alone in higher-risk myelodysplastic syndromes (MDS): efficacy and safety results from Study P-2001 (NCT02610777). Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021. Abstract MDS-344.