Shorter treatments of venetoclax plus azacitidine did not meet similarity criteria for longer treatments in Beat acute myeloid leukemia.
A 14-day schedule of venetoclax (Venclexta) plus azacitidine (Vidaza) did not meet criteria for noninferiority compared with the standard 28-day schedule in patients 60 years and older with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, according to findings from OPTI-AML, a substudy of the phase 1b/2 Beat AML master clinical trial (NCT03013998).¹
Patients who recieved the regimen on a 28-day schedule for 2 cycles (n = 83) achieved a complete response (CR) rate of 49.4% (95% CI, 38.2-60.6) compared with 43% (95% CI, 32.4-54.2) for those who received the 14-day schedule (n = 86).² Moreover, patients in the 28-day schedule arm achieved a CR with partial hematologic recovery (CRh) and CR with incomplete blood count recovery (CRi) at rates of 14.5% and 16.9%, respectively. These respective rates for patients in the 14-day arm were 16.3% and 9.3%. Finally, patients in the 28-day arm achieved an overall response rate (ORR) of 84.3% vs 77.9% among those in the 14-day arm.
“The perception in the blood cancer community is that 28 days of venetoclax for 2 cycles is too toxic; it causes low counts, dose delays, and ultimately, clinicians may shorten the schedule,” lead study author Uma Borate, MBBS, MS, stated in a news release. “Our study shows that shortening treatment to 14 days is not a one-size-fits-all solution for older patients with AML,” she added.¹
Borate is a physician and professor of hematology in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center—James in Columbus.
The randomized substudy enrolled patients who were at least 60 years with newly diagnosed AML. If patients were able or willing to receive chemotherapy, they were excluded from the trial.
Patients were randomly assigned to receive 75 mg/m2 of azacitidine on days 1 to 7 of each cycle plus venetoclax for 2 cycles lasting either 28 or 14 days. Patients on both schedules received once-daily per-label doses of venetoclax.
CR rates was the primary end point of the substudy, with secondary end points of CRh, CRi, minimal residual disease (MRD) negativity, progression-free survival (PFS), overall survival (OS), and safety.
Baseline characteristics revealed that all patients in the substudy (n = 169) had a median age of 73 (range, 60-90) and were mostly White (89.1%) and male (57.4%). Fewer patients were at least 75 years of age (38.5%). ECOG performance statuses broke down as 0 (30.9%), 1 (48.5%), and 2 (20.6%), with 4 patients having an unknown performance status. Patients had a median bone marrow blast rate of 40% (range, 0-98) and a median white blood cell count of 2.6 109/L (range, 0.3-23.6). Some patients had disease harboring NPM1 (5.9%), IDH2 (17.2%), IDH1 (10.1%), FTL3 (11.3%), and TP53 (18.9%) mutations.
Patients with NPM1, IDH2, IDH1, and FLT3 mutations in the 28-day schedule arm achieved respective CR rates of 83.3%, 55.6%, 71.4%, and 77.8%. Conversely, patients with the same respective mutations in the 14-day schedule arm achieved CR rates of 25%, 36.4%, 60%, and 60%.
Patients in the 28-day schedule arm achieved a median PFS of 13.1 months (95% CI, 8.9-21.4) compared with 9.9 months in the 14-day schedule arm (95% CI, 7.2-13.6). Moreover, the median OS rates in the 28- and 14-day schedule arms were 21.4 months (95% CI, 13.4-not reached) and 13.6 months (95% CI, 9.7-22.8), respectively.
MRD negativity rates among responders in each arm were 77.6% and 76.5%, respectively.
Common grade 3 or higher hematologic treatment-emergent adverse effects among all patients were neutropenia (58%), leukopenia (53.3%), thrombocytopenia (52.7%), and anemia (46.2%). Additionally, common grade 3 or higher nonhematologic adverse effects were pneumonia (11.2%), hypoxia (7.7%), hypokalemia (5.3%), and hypotension (4.7%).
“As Beat AML nears its 10-year milestone, this study shows how the trial continues to answer questions that matter in real-world care,” Lore Gruenbaum, PhD, chief scientific officer at Blood Cancer United, added in the news release.1 “We are not only looking for the next breakthrough; we are learning how to use today’s treatments more effectively, safely, and precisely for the patients most likely to benefit,” Gruenbaum concluded. “These findings are an important reminder that reducing treatment intensity may help some patients, but it can also risk compromising response in others. Our goal is to generate the evidence clinicians need to make those decisions with greater confidence.”
