Orelabrutinib produced efficacy improvements vs chemoimmunotherapy in previously untreated chronic lymphocytic leukemia.
Orelabrutinib (Hibruka) demonstrated significant progression-free survival (PFS) improvement vs chemoimmunotherapy and was well tolerated in patients with treatment-naive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to data from a phase 3 trial (NCT04578613).1,2
Trial results showed that orelabrutinib reduced the risk of disease progression or death by 68% compared with chemoimmunotherapy in patients with treatment-naive CLL (HR, 0.32; 95% CI, 0.18-0.58; P < .0001).1 At a median follow-up of 21.4 months, the median PFS was not reached (95% CI, not estimable [NE]-NE) for patients treated with orelabrutinib (n = 91) compared with 19.4 months (95% CI, 16.6-NE) for those given chlorambucil plus rituximab (Rituxan; n = 101). Moreover, investigators noted that patients across all prespecified subgroups, including patients of advanced age and those with Rai stage III/IV disease, del(11q), unmutated IGHV, or bulky disease, experienced consistent benefits with orelabrutinib.
The overall response rate (ORR) was 90.1% with orelabrutinib vs 79.2% with chemoimmunotherapy, and duration of response (DOR) also favored orelabrutinib (HR, 0.30; 95% CI, 0.15-0.60; P = .0003). At 30 months of follow-up, a post hoc analysis showed a complete response rate of 12.1% in the orelabrutinib arm.
Orelabrutinib
“The clinically meaningful benefit, along with favorable safety and maintained quality of life [QOL], indicates a favorable benefit-risk profile of orelabrutinib, establishing it as an effective and safe option for this population,” lead study author Fei Li, MD, PhD, of the Department of Hematology at the First Affiliated Hospital Nanchang University in China, and colleagues wrote in a publication of the data.1
The randomized, phase 3 trial enrolled patients aged 18 to 65 years with a disease accumulation score higher than 6 and a creatinine clearance between 30 and 69 mL per Cockcroft-Gault assessment.4 Patients also needed to have an ECOG performance status of 2 or less and an expected survival that exceeded 6 months.
If patients had a stroke or intracranial hemorrhage within the first 6 months of being randomly assigned or hypersensitivity to any component of orelabrutinib, they were not included in the study.
Patients in the intention-to-treat population were randomly assigned 1:1 to receive once-daily, 150-mg doses of orelabrutinib or 0.5 mg/kg of chlorambucil on days 1 and 15 of the first 6 cycles plus 375 mg/m2 intravenous infusions of rituximab on day 1 of each cycle.
The primary end point of the trial was PFS per independent review committee assessment, with secondary end points of ORR and DOR per independent review committee, safety, and patient-reported outcomes.1,2
The incidence of any-grade treatment-related adverse effects (TRAEs) between orelabrutinib and chemoimmunotherapy arms were comparable.1,2 The respective rates between the 2 arms were 90.1% and 90.8%. The grade 3 or higher TRAE rates were 35.2% and 60.2%, respectively.
Additionally, no treatment-related atrial fibrillation, major bleeding, or second primary malignancies were observed with orelabrutinib.
Patient-reported QOL data showed that overall health status was numerically higher with orelabrutinib than with chemoimmunotherapy. Following cycle 16 of treatment, patients in the orelabrutinib arm experienced a clinically meaningful improvement in patient-reported QOL.2
