Ibrutinib, Venetoclax Combination Therapy May Provide Clinical Benefit to Certain Patients With CLL

The combination therapy of ibrutinib and venetoclax (Ibr+Ven) was superior to chlorambucil and obinutuzumab (Clb+O) in terms of undetectable minimal residual disease (uMRD) responses in elderly or unfit patients with previously untreated chronic lymphocytic leukemia (CLL), according to data from the phase 3 international GLOW trial presented at the American Society of Hematology’s 2021 Annual Meeting and Exposition.

According to the investigators, MRD status is an established predictive marker for progression-free survival (PFS) in CLL following chemoimmunotherapy or fixed-duration treatment with venetoclax and an anti-CD20 antibody. Until the current study, this relationship remained unexplored for the combination of Ibr+Ven, an all-oral, once-daily, fixed-duration treatment with complementary mechanisms of action that work to eliminate CLL subpopulations, according to the investigators.

The study enrolled 211 patients aged ≥65 years or 18-64 years with a cumulative illness rating scale score greater than 6 or creatinine clearance of less than 70 mL/min, excluding individuals with del(17p) or known TP53 mutations. Participants were randomized 1:1—stratified by IGHV mutational and del(11q) status—to receive either Ibr+Ven (3 cycles of ibrutinib lead-in, followed by 12 cycles of Ibr+Ven) or 6 cycles of Clb+O. PFS was the primary endpoint, evaluated by an independent review committee. The rate of uMRD was a secondary endpoint, with MRD samples collected every 3 to 4 months in peripheral blood (PB) and at months 9 and 18 in bone marrow (BM).

The study data showed rates of uMRD were significantly higher in the Ibr+Ven arm of the study, with measurements of 51.9% in BM and 54.7% in PB, compared to 17.1% and 39.0% in the Clb+O arm, respectively. PB/BM uMRD concordance with Ibr+Ven was 92.9%.

In the Ibr+Ven arm, 65.9% of patients with either a complete response or CR with incomplete marrow recovery achieved uMRD in BM, as did 54.9% of patients with a partial response in this arm. In the Clb+O arm, these percentages were 33.3% and 16.9%, respectively. For patients with detectable MRD after treatment with Ibr+Ven, MRD levels remained stable at 3 and 12 months after the end of treatment.

REFERENCE

Munir T, Moreno C, Owen C, et al. First prospective data on minimal residual disease (MRD) outcomes after fixed-duration ibrutinib plus venetoclax (Ibr+Ven) versus chlorambucil plus obinutuzumab (Clb+O) for first-line treatment of CLL in elderly or unfit patients: The Glow study. Presented at: ASH Annual Meeting and Exposition 2021. Accessed December 10, 2021. https://ash.confex.com/ash/2021/webprogram/Paper148666.html