Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
First-line treatment of CLL with sonrotoclax plus zanubrutinib produced quick, deep remissions in almost all patients by 96 weeks.
Who Performed the Research and Where Was it Presented:
Dr. Constantine Tam from Alfred Hospital and Monash University and colleagues presented the results at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2026.
Background:
Combination therapies that work through different mechanisms of action are becoming increasingly common in the treatment of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). While many of these combination therapies use the BCL2 inhibitor venetoclax, sonrotoclax is a new, experimental BCL2 inhibitor,14X more potent than venetoclax, that is currently being tested in clinical trials. An early study of the combination of sonrotoclax and zanubrutinib showed strong results, and here the researchers provide updated results from that Phase 1/1b trial.
Methods and Participants:
Patients with treatment-naïve CLL / SLL initially received zanubrutinib only for 8-12 weeks to reduce tumor burden and the risk of tumor lysis syndrome. Next, sonrotoclax was added with a gradual ramp-up to 320 mg per day. Patients were treated until disease progression, unacceptable toxicity, or 96 weeks (a little less than two years) of therapy. For this analysis, the median follow-up was 31 months (124 weeks).
Results:
- 86 patients received sonrotoclax (320 mg) plus zanubrutinib, with about half of the patients still on treatment (not at 96 weeks yet) at the time of analysis.
- Half of the patients discontinued treatment, mostly due to reaching the end of the 96-week treatment period (85%).
- All patients responded to treatment, and about half (55%) had their blood counts and lymph nodes return to normal (complete response).
- At week 96, 99% of patients had reached undetectable measurable residual disease (uMRD) in the blood.
- Half of the patients reached uMRD in three months or less.
- All patients with deletion 17p or TP53 mutation reached uMRD.
- Thus far, no patients have had their disease progress or revert to measurable residual disease.
- The most common side effects were low white blood cells (38%), bruising (38%), COVID-19 (33%), and upper respiratory tract infection (30%).
- No tumor lysis syndrome occurred.
Conclusions:
Links and Resources:
You can read the actual ASCO abstract here: Effect of first-line treatment of CLL / SLL with the all-oral combination of sonrotoclax (sonro) and zanubrutinib (zanu) on minimal residual disease (uMRD) rates, including in patients with del(17p)/TP53
Take care of yourself first.
Ann Liu, PhD
