“Our work demonstrates that [patients with] AML on the extremes of older age will be handled efficiently with VEN-HMA, and a subset of those sufferers have extended survival,” in line with the examine authors.
Combining venetoclax (Venclexta) with hypomethylating brokers (VEN-HMA) could enhance survival in a subset of octo- and nonagenarian sufferers with acute myeloid leukemia (AML), in line with findings from a retrospective examine printed in Blood Neoplasia.
Amongst all sufferers, the median total survival (OS) was 8.1 months (95% CI, 6.7-10.2). Moreover, the median OS was 13.2 months (95% CI, 9.4-16.4) in those that had a response vs 4.1 months (95% CI, 2.5-6.3) in these with no response (P <.001); the median OS for these with a whole response (CR) was 13.8 months (95% CI, 9.4-21.1; P <.001). Investigators reported a median OS of 10.2 months for sufferers with newly recognized AML with out prior myelodysplastic syndrome (MDS), 6.4 months in these with newly recognized illness and prior MDS, and 9.2 months in sufferers with relapsed/refractory AML (P = .13).
The median OS for sufferers with any TP53 mutation (n = 31) was 6.4 months, which investigators highlighted as worse in contrast with all different teams (P = .0048). The median OS was 9.1 months in these with any RAS pathway mutation (n = 20) in contrast with 7.8 months in these with no RAS mutation (P = .96).
The median OS for sufferers with a FLT3-ITD mutation (n = 12) was 12.2 months vs 7.8 months in these with FLT3-ITD wild-type illness (P = .44). For these with a FLT3-ITD mutation however not a TP53 mutation (n = 10), the median OS was 19.5 months (P = .55). Therapy yielded a median OS of 6.3 months in sufferers with advanced karyotype (P = .0004).
“Our work demonstrates that [patients with] AML on the extremes of older age will be handled efficiently with VEN-HMA, and a subset of those sufferers have extended survival,” Ellen Madarang, a scientific pharmacist within the Division of Pharmacy on the College of Miami Sylvester Complete Most cancers Middle, and coauthors wrote.
“Aged sufferers could profit from important dose reductions, significantly after reaching response. In sufferers who achieved a composite full remission [CRc], the median ultimate dose and period of venetoclax was 200 mg each day for 21 days each 35 days,” they added.
Investigators of this multi-center examine assessed sufferers throughout 6 establishments in america and Italy. Sufferers acquired venetoclax at 200 mg plus average CYP3A4 inhibitors or at 100 mg together with sturdy CYP3A4 inhibitors at a goal dose of 400 mg.
The examine’s main finish level was OS. Secondary finish factors included the CRc price, median venetoclax dose and period at cycle 1 and final follow-up, VEN-HMA cycle size, and dose reductions. Security finish factors included grade 3 or greater treatment-emergent opposed results (TEAEs) resembling anemia, thrombocytopenia, neutropenia, and febrile neutropenia.
Amongst 154 sufferers who had been 80 years and older with AML, 77% had newly recognized illness, 10% had relapsed/refractory illness, and 14% had unknown illness kind. Of these with newly recognized illness, most had newly recognized AML with out prior MDS (56%).
The median age was 82 years (vary, 80-92), and most sufferers had been male (69%). Amongst 140 sufferers with evaluable molecular information, frequent mutations included TP53 mutations (22%), IDH1/2 mutations (19%), NPM1 mutations (12%), and FLT3-ITD mutations (8%).
In line with multivariate evaluation, components that correlated with worse OS included an ECOG efficiency standing of three or greater (HR, 3.57; 95% CI, 1.35-9.45; P = .010), intermediate-risk illness (HR, 3.56; 95% CI, 1.07-11.87; P = .039), opposed danger (HR, 3.31; 95% CI, 0.99-11.05; P = .052), TP53 mutations (HR, 1.96; 95% CI, 1.14-3.36; P = .015), and prior MDS (HR, 1.72; 95% CI, 1.08-2.73; P = .022). Sufferers who acquired a shorter period of venetoclax therapy at 14 or fewer days skilled enhancements in OS in contrast with those that acquired therapy for greater than 14 days (HR, 2.47; 95% CI, 1.52-4.02; P <.001).
Knowledge highlighted a CRc price of 57% (n = 87/154) and a CR price of 41% (n = 63/154) throughout the intent-to-treat inhabitants. Decrease response charges had been reported in these with relapsed/refractory or newly recognized AML with prior MDS and sufferers with prior therapy with HMAs for MDS or AML.
Total, 36 (23%) sufferers had been nonetheless in remission on the time of the ultimate information cutoff, and 31 (20%) had been nonetheless receiving therapy with VEN-HMA. The mortality charges had been 8.5% at 30 days and 17% at 60 days.
Grade 3/4 TEAEs included neutropenia (53%), anemia (50%), thrombocytopenia (48%), and neutropenic fever (46%). Of the identified causes, most sufferers died as a consequence of illness development or relapse (60%), sepsis (8%), and components unrelated to AML (8%).
Reference
Madarang E, Lykon J, Zhao W, et al. Venetoclax and hypomethylating brokers in octo- and nonagenarians with acute myeloid leukemia. Blood Neoplasia. 2024;100016. doi:10.1016/j.bneo.2024.100016
