Fixed-Duration AV Is a Compelling Option, With Important Caveats: Adam Kittai, MD

In part 2 of his recent interview with The American Journal of Managed Care^®, Adam Kittai, MD, addressed how he counsels patients choosing between acalabrutinib plus venetoclax (AV) and continuous Bruton tyrosine kinase (BTK) inhibitor therapy, as well as the safety considerations that guide those conversations.

Kittai is director, CLL Program, Perlmutter Cancer Center, and director, Lymphoma Program, Perlmutter Cancer Center - Long Island, at NYU Langone Health.

Although continuous BTK inhibitor therapy offers real-world convenience with 1 oral pill daily, Kittai noted that younger patients with chronic lymphocytic leukemia (CLL) may face cumulative toxicities over time that warrant discussion. For a patient in their 50s with cardiac risk factors, prediabetes, or excess weight, adding long-term hypertension through indefinite BTK inhibition may not be ideal; the typical age at CLL diagnosis is 70 years.¹

AV, administered for only 14 cycles, sidesteps that concern. Data from the AMPLIFY trial (NCT03836261) showed a favorable safety profile, with atrial fibrillation or flutter occurring in just 0.7% of patients and major hemorrhage in only 1.0%.² Tumor lysis syndrome, a hallmark concern with venetoclax, occurred in just 1 of 291 patients, a finding Kittai attributes to the 2-cycle BTK inhibitor priming strategy.

“If somebody was coming in really committed to time-limited therapy and wanted oral therapy without the infusion, that’d be somebody I would be fine doing it,” Kittai said. “Just talking to them about it first and letting them know that maybe it’s not what I prefer.”

Despite these reassuring data, Kittai noted he remains vigilant about bleeding risk, particularly in patients requiring concurrent anticoagulation. Those on aspirin, Plavix, and acalabrutinib simultaneously prompt him to explore dose modifications or engage cardiology regarding whether anticoagulation is truly mandated.

Infection also warrants attention. The grade 3 infection rate with AV was 12.4% in AMPLIFY, comparable with chemotherapy, and Kittai said he counsels patients to report fever or illness promptly. Labs are checked at least monthly during venetoclax administration.

Kittai characterized AV as a safe, time-limited regimen well-suited for patients prioritizing oral, fixed-duration therapy. However, he is candid about its limitations: no long-term follow-up, no direct comparisons to continuous therapy or venetoclax plus obinutuzumab yet, and uncertainty around high-risk disease features. For patients committed to avoiding indefinite treatment, it remains a viable path, with an informed conversation first.

References

1. Key statistics for chronic lymphocytic leukemia (CLL). American Cancer Society. Updated January 13, 2026. Accessed May 21, 2026. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html
2. Study of acalbrutinib (ACP-196) in combination with venetoclax (ABT-199), with and without obinutuzumab (GA101) versus chemoimmunotherapy for previously untreated CLL (AMPLIFY). ClinicalTrials.gov. Updated December 27, 2024. Accessed May 21, 2026. https://clinicaltrials.gov/study/NCT03836261