Therapies For Managing Patients With Treatment-Naive CLL

  • Although the BTK inhibitor ibrutinib has revolutionized chronic lymphocytic leukemia (CLL) treatment, next-generation treatments such as acalabrutinib and zanubrutinib show added promise for progression-free survival.
  • Clinical trials that directly compared the effectiveness of acalabrutinib and Zanubrutinib to ibrutinib in relapsed/refractory patients found that “progression-free survival averaging 38 months, improved tolerability with fewer cardiovascular adverse events.”
  • Dr. Adam Kittai, an associate professor of medicine at Mount Sinai, believes acalabrutinib and Zanubrutinib are “safer” than ibrutinib, citing clinical trials that compare the drugs.
  • Another therapy on the table is Venetoclax (Venclyxto), a BCL2 inhibitor that helps slow cancer progression. It is often combined with obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody integrated through infusion.

Thanks to treatment advances for chronic lymphocytic leukemia (CLL), physicians have three different BTK inhibitors at their fingertips: ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa).

Ibrutinib helped revolutionize CLL treatment, but next-generation therapies show promise, factoring in toxicity and resistance for patients needing continuous treatment.

Another therapy on the table is Venetoclax (Venclyxto), a BCL2 inhibitor that helps slow cancer progression. It is often combined with obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody integrated through infusion.

Dr. Adam Kittai, Associate Professor of Medicine at Mount Sinai in New York, explains to SurvivorNet that his approach to treating his CLL patients revolves around patient preference for treatment.

“Do they want a time-limited therapy, or do they want a continuous therapy?” Dr. Kittai said.

Why Dr. Kittai Prefers Certain BTK Inhibitors Over Another

Dr. Kittai has a rich background in clinical trials and has led several research articles published in medical journals. His observations of clinical trials involving ibrutinib, acalabrutinib, and zanubrutinib led him to conclude that acalabrutinib and Zanubrutinib are “safer.”

Research published in “Cancers” draws attention to head-to-head comparisons of two phase III clinical trials for acalabrutinib and zanubrutinib compared to ibrutinib in a relapsed/refractory population.

Researchers concluded in the New England Journal of Medicine that during the ALPINE trial, “at a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival.”

The ELEVATE-RR trial also compared acalabrutinib to ibrutinib in patients with previously treated high-risk CLL. Researchers noted in Blood Cancer Journal, “acalabrutinib met its primary endpoint of progression-free survival (PFS) noninferiority with a median PFS of 38.4 months…demonstrating improved tolerability with fewer cardiovascular adverse events” compared to ibrutinib.

“The reason why I don’t use ibrutinib anymore is that there were two phases, three randomized trials published in the second line or relapse setting, comparing acalabrutinib to ibrutinib and zanubrutinib to ibrutinib, which both showed that the second generation BTK inhibitors, acalabrutinib, and zanubrutinib were safer than ibrutinib,” Dr. Kittai explained.

“When I’m deciding what to treat a patient with who sees me in a clinic, I’m really between acalabrutinib and zanubrutinib and venetoclax plus Obinutuzumab,” Dr. Kittai added.