Alternating Venetoclax Regimens Show Feasibility in Older AML Population

Alternating cladribine plus low-dose cytarabine and venetoclax (Venclexta) with azacitidine (Vidaza) plus venetoclax showed feasibility and activity in a community setting of older patients with acute myeloid leukemia (AML), according to findings from a poster presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

The median overall survival (OS) and composite complete response (CRc) rate, respectively, were 14.5 months and 60% across the overall cohort (n = 82), 14.5 months and 60% among patients treated in the first line (n = 66), 12.0 months and 63% among those without prior hypomethylating agents (HMAs) treated in the first line (n = 54), and 21.1 months and 41.7% among those with prior HMAs treated in the frontline setting (n = 12). Additionally, the median OS and CRc rate were 16.2 months and 62.5% among those treated in the second line and beyond (n = 16), 6.3 months and 66.7% among patients who received no prior HMAs treated in the second line and beyond (n = 6), and 16.3 months and 60% among those with prior HMAs who received treatment in the second line or later (n = 10).

Among patients with favorable ELN-proxy risk who received frontline treatment (n = 8), the median OS was 44.4 months, and the CRc rate was 62.5%. These respective values were not reached and 63.6% among patients with intermediate ELN-proxy risk (n = 11) and 8.9 months and 57.4% among those with adverse risk (n = 47).

The median OS and CRc rate, respectively, were 9.1 months and 38.9% among patients with TP53-mutated AML (n = 18). Among those with TP53 mutations, the respective values were 9.1 months and 37.5% for patients who received frontline treatment (n = 16) and 0.4 months and 50.0% for those who received treatment in the second line or later (n = 2).

“Alternating [cladribine plus low-dose cytarabine and venetoclax with azacitidine/venetoclax] is feasible and active in a community setting, in patients markedly older than the [overall MD Anderson Cancer Center] trial cohort,” Janvi Bhatia, BS, of Community Hospitals Network/MD Anderson in Indianapolis, Indiana, wrote with coauthors in the poster.¹ “Extension to relapsed [or] prior-treated AML produces CRc comparable to frontline [care, supporting] prospective evaluation in [second-line and later] disease. Shorter community OS reflects older age, fewer transplants, limited follow-up; meaningful activity is retained in patients excluded from the original trial.”

According to the investigators, the alternating venetoclax-based regimen previously demonstrated efficacy as frontline therapy among 190 older patients with AML at MD Anderson Cancer Center as part of a phase 2 study (NCT03586609).² The published cohort was a single-center, single-arm, exclusively frontline trial that included patients with a median age of 68 years; 13% of whom were 75 years or older. This trial, the investigators wrote, left some open questions regarding the feasibility of the regimen in community practice, patients who are 75 years and older, and patients with relapsed/refractory disease or prior HMA exposure.

Investigators of this community-based, real-world study assessed the aforementioned regimen while emphasizing older patients, extension of treatment to previously treated AML, and feasibility of care outside a tertiary academic center. The study’s primary end points included the CRc rate and OS from the time the first cycle of treatment started to death. Investigators used Kaplan-Meier models to estimate median OS and conducted a sensitivity analysis of first-line treatment outcomes while excluding any prior HMA exposure.

Among patients who received frontline treatment (n = 66) or care in the second line or beyond (n = 16), the median age was 74 years and 69 years, respectively. Of note, 76% of patients in the frontline population had adverse ELN-proxy risk compared with 64% of patients in the MDACC trial.

References

1. Bhatia J, Bedano PM, Bhatia S, et al. Cladribine (CLAD) + low-dose AraC (LDAC) + venetoclax (VEN) in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome: real-world analysis from a large community-based oncology practice. J Clin Oncol. 2026;44(suppl 16):6542. doi:10.1200/JCO.2026.44.16_suppl.6542
2. Kadia TM, Bataller A, Bazinet A, et al. Cladribine with low-dose cytarabine and venetoclax alternating with azacitidine and venetoclax for newly diagnosed acute myeloid leukemia. Am J Hematol. 2026;101(7):1737-1747. doi:10.1002/ajh.70328