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Real-World Risk of Infusion Reactions and Efficacy of Frontline Obinutuzumab-Chlorambucil for CLL
Study findings suggest risk of infusion reactions in patients with chronic lymphocytic leukemia (CLL) receiving obinutuzumab can be reduced using chlorambucil before obinutuzumab administration and by using a slow initial obinutuzumab infusion rate (BMC Cancer. 2022; 22[1]:148. doi:10.1186/s12885-022-09256-2).
Prior studies have shown that among unfit patients with CLL, obinutuzumab was associated with improved progression free survival (PFS) and response rates compared to other regimens.
In this study, Nicole Bourrier, BSc, Max Rady College of Medicine, Winnipeg, MB, Canada, and colleagues aimed to evaluate the efficacy of obinutuzumab plus chlorambucil regimen vs other available treatments and examine risk of first-dose infusion reactions among patients with CLL.
Bourrier and colleagues performed a retrospective chart review for patients with CLL who received obinutuzumab from January 1, 2014 to December 31, 2017 at CancerCare Manitoba.
Data was compared between patients receiving obinutuzumab vs other frontline therapies, including patient demographics, toxicity, and duration and dosing of obinutuzumab treatment. Time-to-next-treatment, overall survival and PFS for patients treated with obinutuzumab were evaluated using Kaplan–Meier curves.
A multivariable logistic regression model examined associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy.
Among participants, 47% of those receiving frontline therapy were treated with chlorambucil and obinutuzumab. Of the 67 patients receiving obinutuzumab, 36 were males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years.
Slower infusion rates and using chlorambucil before starting obinutuzumab treatment resulted in lower rates of grade 3 and 4 obinutuzumab IRRs (6%) compared to the CLL11 clinical trial (20%). The full dosage of chlorambucil was difficult for many patients to tolerate, with only 26 patients (38.8%) able to escalate to the full dose of 0.5 mg/kg. Only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil.
“First dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate,” concluded Bourrier and colleagues, adding, “Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.”
