According to data that were presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, venetoclax plus azacitidine led to higher rates of complete remission (CR), a longer duration of response (DoR), and median overall survival (OS) than azacitidine monotherapy in treatment-naïve patients with therapy-related myeloid neoplasms (tMN) and antecedent myelodysplastic syndrome or myeloproliferative neoplasms (A-MDS/MPNs).

“Patients with tMN or A-MDS/MPNs may have poor outcomes due to age and adverse genetic/karyotypic features. In the VIALE-A study, patients with tMN and A-MDS/MPN unfit for intensive chemotherapy treated with venetoclax and azacitidine demonstrated superior response rates and overall survival (OS) than azacitidine alone,” explained Vinod Pullarkat, MD, City of Hope Comprehensive Cancer Center, Duarte, California, and colleagues.

By conducting a pooled analysis of data from the VIALE-A trial and a phase 1b study where patients received venetoclax plus azacitidine, Dr Pullarkat et al sought to describe the safety and efficacy of venetoclax plus azacitidine among patients with tMN and A-MDS/MPNs.

Patients in these studies were aged ≥18 years, treatment-naïve with no prior exposure to hypomethylating agents, and not eligible to receive intensive chemotherapy.

Patients given the combination regimen received venetoclax 400 mg on days 1 to 28 of a 28-day cycle and azacitidine 75 mg/m² on days 1 to 7. The investigators looked at the composite CR rate (CRc; CR plus CR with incomplete hematologic recovery), DoR, and OS. In addition, they assessed disease in accordance with modified International Working Group response criteria for AML.

Overall, tMN was observed in 31 and 9 patients given venetoclax plus azacitidine and placebo plus azacitidine, respectively, and A-MDS/MPN in 59 and 26 patients.

Dr Pullarkat and co-investigators observed poor-risk cytogenetics were observed in 18 (58%) and 6 (67%) with tMN (5 or 5q deletion [del], 4/1 ; 7 or 7q del: 6/1 ; complex [≥3 clonal abnormalities], 10/4), and 19 (32%) and 13 (50%) with A-MDS/MPN (5 or 5q del: 10/5; 7 or7q del: 6/1; complex: 14/9).

“TP53 mutations were observed in 5/3 patients with tMN and 8/0 patients with A-MDS/MPN,” they noted.

Among patients with tMN—who were given a median of 5 and 4 treatment cycles of venetoclax plus azacitidine or placebo plus azacitidine, respectively—CRc was achieved by 19 (61%)/1 (11%). The mDoR was not reached (NR; 95% CI, 17.8 to NR) versus 8.5 (95% CI, NR to NR) months for each treatment arm, respectively. The mOS was 16.4 (95% CI, 4.1 to NR) versus 11.3 (95% CI, 0.6-17.5) months.

Among patients with A-MDS/MPNs—who were given a median of 9 and 5 treatment cycles of venetoclax plus azacitidine or placebo plus azacitidine, respectively—CRc was achieved by 39 (66%)/7 (27%) patients with a mDoR of 17.3 (95% CI, 9.6 to NR) and 5.8 (95% CI, 1.1 to NR) months, respectively. The mOS was 15.9 (95% CI, 11.5, NR) versus 10.1 (4.7, 14.5) months.

Frequently documented adverse events of grade ≥3 with venetoclax plus azacitidine or placebo plus azacitidine were febrile neutropenia (tMN: 39%/11% and A-MDS/MPN: 36%/12%); neutropenia (tMN: 29%/33%; A-MDS/MPN: 39%31%); and thrombocytopenia (tMN: 32%/33%; A-MDS/MPN: 39%/62%).

“Venetoclax plus azacitidine compared to azacitidine monotherapy resulted in higher CRc rates with longer DoR and median OS among treatment-naïve patients with tMN and A-MDS/MPN ineligible for intensive chemotherapy,” Dr Pullarkat and colleagues reported.

“The safety profile was similar to overall patients with the venetoclax plus azacitidine combination,” they added.

Pullarkat V, Pratz K, Dohner H, et al. Venetoclax and azacitidine combination in chemotherapy ineligible untreated patients with therapy-related myeloid neoplasms, antecedent myelodysplastic syndromes, or myelodysplastic/myeloproliferative neoplasms. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 7011.