Brief from ASH 2021: News and Advances in CLL Treatment

Venetoclax and Zanubrutinib in Previously Untreated Patients with CLL or SLL

One of the oral presentations discussed the combination of venetoclax and zanubrutinib in previously untreated patients with CLL or small lymphocytic lymphoma (SLL) with a 17p deletion. These were early results from the D arm of the SEQUOIA study.

Zanubrutinib is a representative of the new generation of selective Bruton tyrosine kinase inhibitors (BTKi), but has not yet been approved for the indication of CLL. According to the study, the combination of venetoclax and zanubrutinib (160 mg twice daily) administered after a preceding treatment with only zanubrutinib for 3 months may lead to the achievement of undetectable/minimally measurable residual disease (MRD).

The study focused on patients with the unfavorable prognostic marker del17p and found that up to 30 out of 31 patients responded to the combination, with no newly discovered safety signals. The median follow-up in the study was 9.7 months. These are encouraging preliminary results for such a high-risk group of patients, and the study is ongoing.

Time-Limited Administration of Venetoclax and Ibrutinib in Patients with R/R CLL

Another interesting communication concerned the evaluation of response to time-limited administration of venetoclax and ibrutinib in patients with relapsed or refractory CLL after prior immunochemotherapy, who had undetectable MRD. This was a primary analysis of the randomized phase II Vision HO141 study.

BTKi-naïve patients started treatment with ibrutinib alone for 2 cycles, and from the 3rd cycle, venetoclax was added; both agents were administered together until cycle 15. Patients achieving at least a partial remission and undetectable MRD in blood and bone marrow in cycle 15 were randomized to either receive maintenance therapy with ibrutinib or were followed without maintenance therapy. If MRD positivity was subsequently detected in the non-maintenance arm, combination therapy with venetoclax and ibrutinib was reinitiated. MRD-positive patients in cycle 15 continued on ibrutinib.

The study included 225 patients. Interim results showed that time-limited combination therapy represents an excellent salvage therapy in case of progression following immunochemotherapy, with an overall response rate of 86%. Documented progression-free survival (PFS) at 1 year after stopping treatment was 98%. For all MRD-positive patients, treatment could be successfully reinitiated to control CLL. MRD levels remained stable during the first year in patients who continued on ibrutinib monotherapy after the combination therapy ended. There was no difference in achieving undetectable MRD in blood at cycle 15 depending on the presence of TP53 gene mutation.

The advantage of this fixed combination is the possibility of oral administration. The study also confirmed a potential new trend, specifically the initiation of treatment at the onset of MRD positivity rather than waiting until clinical progression.

(eza)

Sources:
1. Koffman B. ASH 2021: Report from the first day − December 11, 2021. CLL Society, 2021 Dec 12. Available at: https://cllsociety.org/2021/12/ash-2021-report-from-the-first-day-dec-11-2021
2. Tedeschi A., Ferrant E., Flinn I. W. et al. 67 Zanubrutinib in combination with venetoclax for patients with treatment-naïve chronic lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p): early results from arm D of the SEQUOIA (BGB-3111-304) trial. 63^rd ASH Annual Meeting, Atlanta, 2022 Dec 11. Available at: https://ash.confex.com/ash/2021/webprogram/Paper144336.html
3. Niemann C. U., Dubois J., Brieghel C. et al. 69 Time-limited venetoclax and ibrutinib for patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have undetectable MRD – primary analysis from the randomized phase II vision HO141 trial. 63^rd ASH Annual Meeting, Atlanta, 2022 Dec 11. Available at: https://ash.confex.com/ash/2021/webprogram/Paper148630.html