Society of Hematologic Oncology Annual Meeting
Society of Hematologic Oncology Annual Meeting
Source/Disclosures
Source:

Watts J, et al. Abstract MDS-336. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting). Sept. 9-12, 2020.

Disclosures: Please see the abstract for all other authors’ relevant financial disclosures.
September 14, 2020
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Pevonedistat plus azacitidine prolongs EFS in higher-risk myelodysplastic syndrome

Source/Disclosures
Source:

Watts J, et al. Abstract MDS-336. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting). Sept. 9-12, 2020.

Disclosures: Please see the abstract for all other authors’ relevant financial disclosures.
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The addition of pevonedistat to azacitidine prolonged EFS among patients with higher-risk myelodysplastic syndrome, according to results of a phase 2 study presented at Society of Hematologic Oncology Annual Meeting.

The safety profile of the combination appeared comparable to that of azacitidine (Vidaza, Celgene) alone, researchers noted.

Infographic showing median EFS among patients with higher-risk myelodysplastic syndrome

Pevonedistat (TAK-924, Takeda), a small-molecule inhibitor of NEDD8-activating enzyme, works by disrupting proteasomal degradation of select proteins.

Justin M. Watts, MD, hematologist/oncologist at Sylvester Comprehensive Cancer Center and assistant professor at University of Miami, and colleagues evaluated data from patients with higher-risk myelodysplastic syndrome/chronic myelomonocytic leukemia — defined as those with a Revised International Prognostic Scoring System score of 3 or higher — or low-blast count acute myeloid leukemia naive to treatment with hypomethylating agents.

Researchers randomly assigned 58 patients to 20 mg/m2 IV pevonedistat at on days 1, 3, and 5 in combination with 75 mg/m2 IV azacitidine on days 1 through 5, 8 and 9 of each 28-day cycle. The other 62 patients received azacitidine alone.

EFS served as the primary endpoint.

OS, overall response rate and safety served as secondary endpoints. Researchers evaluated patient-reported quality of life using the European Organization for Research and Treatment of Cancer Questionnaire-C30.

In the intent-to-treat population of 120 patients, researchers reported a trend toward improved EFS (21 months vs. 16.6 months; HR = 0.67; 95% CI , 0.42-1.05) and OS (21.8 months vs. 19 months; HR = 0.8; 95% CI, 0.51-1.26) among patients who received the combination compared with those who received azacitidine alone, although the improvements did not reach statistical significance.

Among 67 patients with higher-risk myelodysplastic syndrome, researchers observed improved EFS (median, 20.2 months vs. 14.8 months; HR = 0.54; 95% CI, 0.29-1) and a trend toward improved OS (median, 23.9 months vs. 19.1 months; HR = 0.7; 95% CI, 0.39-1.27) among those who received pevonedistat plus azacitidine.

Among 59 response-evaluable patients with higher-risk MDS, ORR was 79% with the combination vs. 57% with azacitidine alone. Researchers reported a median duration of response of 34.6 months in the combination therapy group and 13.1 months in the monotherapy group.

Median azacitidine dose intensity remained at 98% among patients with higher-risk MDS in both treatment groups.

Ninety-four percent of patients who received combination therapy, as well as 83% of patients who received monotherapy, experienced grade 3 or higher adverse events. The most common of these included neutropenia (combination, 38% vs. monotherapy, 37%) and febrile neutropenia (22% vs. 31%).

Researchers observed no difference in patient-reported quality of life between both groups.