Safety and Feasibility of Short-Duration Infusion Obinutuzumab With Venetoclax in Patients With Chronic Lymphocytic Leukemia: A Prospective Observational Study

Presenting Author: Matthew Lei, PharmD, Department of Pharmacy, Massachusetts General Hospital, Boston, MA

Co-Authors: Uvette Lou, PharmD, Mark Sorial, PharmD, Brenna Rowen, PharmD, E. Bridget Kim, PharmD, Rana Ruchi, PharmD, and Andrea Medrano, BS, PharmD Candidate, Department of Pharmacy, Massachusetts General Hospital, Boston, MA; Priyanka Pullarkat, MD, J. Erika Haydu, MD, PhD, Jeffrey Barnes, MD, Ephraim Hochberg, MD, P. Connor Johnson, MD, Ronald Takvorian, MD, Jeremy Abramson, MD, MS, Jacob D. Soumerai, MD, Julia Lynch, APRN, Emily Patterson, APRN, Katherine Thorp, APRN, Maryanne Sherbourne, APRN, Brianne McGree, APRN, Michelle Knowles, APRN, Josie Ford, BS, Ronald Nemec, BA, Catherine Cho, BA, Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA; Robert Redd, MS, Department of Data Science, Dana-Farber Cancer Institute, Boston, MA

BACKGROUND: Obinutuzumab is approved in combination with venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and with chemotherapy for classic follicular lymphoma (cFL). Infusion-related reactions (IRRs) occur in 60% (grade ≥3 IRRs: 10%) of patients with CLL/SLL receiving obinutuzumab. During cycles (C) 2 to 6 (C2-6), obinutuzumab was infused over ≥195 minutes. A 90-minute short-duration infusion (SDI) obinutuzumab starting with C2 is safe in patients with cFL without grade ≥3 IRR in C1. Data on SDI obinutuzumab in CLL/SLL are limited. We report a prospective observational study to evaluate the safety of SDI obinutuzumab in patients with CLL/SLL receiving treatment with venetoclax.

OBJECTIVES: To evaluate the proportion of patients with grade ≥3 IRR with 90-minute SDI obinutuzumab in patients with CLL/SLL receiving venetoclax.

METHODS: This prospective, exact single-stage, observational study included the first 28 consecutive patients with treatment-naïve or relapsed/refractory CLL/SLL and who received venetoclax identified via a lymphoid malignancy patient registry approved by the institutional review board. Dosing, schedule, premedications, and infusion rates were according to the obinutuzumab prescribing information. Starting with C2, absent grade ≥3 IRR in C1 and an absolute lymphocyte count of <5000/μL on day (D) of treatment, obinutuzumab was administered at 100 mg per hour for 30 minutes, then 900 mg per hour for approximately 60 minutes. The primary end point included the proportion of patients with grade ≥3 IRR defined per Common Terminology Criteria for Adverse Events v5.0. Response was evaluated per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.

RESULTS: Between January 23, 2023, and April 11, 2024, 28 consecutive patients with CLL/SLL received venetoclax with SDI obinutuzumab. The median age was 65 years (range, 27-88), and 79% were treatment-naïve. Absolute lymphocyte count was ≥25,000/μL before C1D1 in 54% and ≥5000/μL before C2D1 in 0%. All patients received SDI obinutuzumab on C2D1. None discontinued obinutuzumab prematurely; the median number of obinutuzumab Cs was 6 (interquartile range, 6-6) and all completed ≥4 Cs. All patients achieved an iwCLL objective response. No patients had a grade ≥3 IRR. The incidence of grade 1 to 2 IRRs was 53.6%. All IRRs were grade 2 and occurred on C1D1, including 1 patient with recurrent grade 2 IRR on D2, and none occurred on days 8-15 of C1. One had an IRR after C1; this was a grade 2 IRR occurring on C3D1.

CONCLUSION: SDI obinutuzumab with venetoclax was safe in patients with CLL/SLL. This study met the primary end point and supports adoption of SDI obinutuzumab starting in C2 absent grade ≥3 IRR during C1 when absolute lymphocyte count <5000/μL.

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