Real-World Efficacy, Safety of First-Line Venetoclax-Based Combination Therapy for AML

Prapti Patel, MD, Department of Medical Oncology, University of Texas, Southwestern Medical Center, Dallas, TX, discusses data from a real-world study analyzing outcomes of older patients with acute myeloid leukemia (AML) who received first-line venetoclax-based combination therapy. 

These findings were presented at the 2021 ASH Annual Meeting.

Transcript: 

Hello. My name is Prapti Patel from the Simmons Cancer Center at University of Texas Southwestern in Dallas, Texas. I will be reviewing the data from our study titled "Frontline Venetoclax Based Combination Therapy in Older Adults with Acute Myeloid Leukemia Treated in the Real-World Setting -- A Multi-Institutional Retrospective Study."

This data was presented at the 2021 ASH meeting. What we do know is that AML is a disease of the older population, with a median diagnosis of about 68 years. Outcomes remain poor for patients older than 60 years of age, who are unfit to receive intensive chemotherapy.

Venetoclax in combination with hypomethylating agents or low-dose cytarabine has become the new standard of care based on the VIALE-A and VIALE-C confirmatory trials. Real-world data can provide valuable insights into patients with AML treated with ven-based combination therapy outside of a clinical trial setting.

This data is a retrospective observational study using the COTA database, which includes patient data for about 3000 patients with AML. The COTA database is a USA-based deidentified dataset, comprised of longitudinal electronic health record-derived real-world data.

Data points are extracted manually by trained clinical abstractors and supplemented with structured data from the electronic health record. Inclusion criteria is as follows: 65 years or older; diagnosed with AML after January 1st, 2019; and patients received first-line ven-based combination therapy with either azacitidine, decitabine, or low-dose cytarabine.

112 patients met these criteria, and 54 were treated with venetoclax/azacitidine, 52 with venetoclax/decitabine, and 6 with venetoclax/low-dose cytarabine. Real-world overall response rate, overall survival, and adverse events were calculated by treatment growth.

The real-world overall response rate is defined as the proportion of patients that achieved a complete response or a partial response. Responses were defined per treating physician as complete response, partial response, or progressive disease. Survival outcomes were calculated using the Kaplan-Meier method and compared amongst groups in the log-rank test.

Patients were predominantly treated in a community setting. Per the ELN risk criteria, 6.2% had favorable, 19.6% had intermediate-risk, and 62.5% had high-risk AML. Five of the 6 patients or 83% received venetoclax/low-dose cytarabine and had secondary AML, whereas approximately 30% of the patients receiving ven- and HMA-based therapy had secondary AML.

The most common molecular abnormalities across the cohort were TP53 in about 38%, TET2 in about 27%, ASXL1 in 27%, and DNMT3A in 20%. A majority of these patients had poor-risk cytogenetic features such as complex karyotype or among so many karyotype.

The median overall survival was similar across all the treatment groups. It was 11.3 months in the ven/aza group, 6.5 months in the ven/low-dose cytarabine group, and 13.9 months in the ven/decitabine group. Interestingly, there were no differences in the overall survival between the three groups, and there was no statistical significance.

The real-world overall response rate defined as a partial response or better by treatment was about 57% for ven/decitabine, 55% for ven/azacitidine, and 33% for ven/low-dose cytarabine. Again, the differences in the real-world response rates between these three treatment groups was not statistically significant.

The most common toxicities were quite predictable, which was myelosuppression/cytopenias, and the most common reason for treatment discontinuation was toxicity in about a third of patients, followed by progression or inadequate response in about 11% of patients. Our real-world population of patients treated with ven-based combination therapy were predominantly treated in the community setting and had high risk for ELN criteria.

The overall survival in the real-world overall response rates were similar across all the treatment groups, and the most common reason for treatment discontinuation was toxicity primarily due to myelosuppression or persistent cytopenias. Ven/HMA response rates were lower and survival outcomes were shorter than those reported in the VIALE-A trial.

This underscores the importance of studying novel therapies using real-world data, and comparability of real worlds overall response is limited by the lack of uniform response criteria utilized in the real-world setting.

This concludes my presentation and I'd like to take a moment to thank the patients of this study, without whom the study advancement and the treatment of AML would not be possible. Thank you.