Acalabrutinib with or without obinutuzumab significantly enhanced progression-free survival outcomes compared with combination obinutuzumab-chlorambucil chemoimmunotherapy. These findings led researchers to suggest its use as first-line treatment for patients with chronic lymphocytic leukemia (CLL) in a paper published in The Lancet.
A team of international researchers conducted ELEVATE-TN, a phase 3, open-label study (ClinicalTrials.gov Identifier: NCT02475681), to determine how effectively acalabrutinib (monotherapy or in combination with obinutuzumab) could treat CLL compared with obinutuzumab-chlorambucil in treatment-naive patients.
Patients with untreated CLL who were 65 years or younger or patients who were between ages 18 and 65 years with creatinine clearance of 30 mL/min to 69 mL/min were invited to participate in the study. Those with significant cardiovascular disease and those taking warfarin or equivalent vitamin K antagonists were excluded from the study.
A total of 535 patients were randomly assigned to receive acalabrutinib-obinutuzumab (179 participants), acalabrutinib monotherapy (179 participants), or obinutuzumab-chlorambucil (177 participants), all treatments were administered in 28-day cycles. The primary outcome was progression-free survival between both combination treatment cohorts. Participants treated with obinutuzumab-chlorambucil who progressed were permitted to crossover to the acalabrutinib cohort.
Median progression-free survival at median follow-up of 28.3 months was longer among participants in acalabrutinib-obinutuzumab and acalabrutinib monotherapy groups compared with obinutuzumab-chlorambucil therapy participants (hazard ratio, 0.10 and 0.20, respectively).
At 24 months, progression-free survival was observed in 93%, 87%, and 47% of patients receiving acalabrutinib combination, acalabrutinib monotherapy, and obinutuzumab-chlorambucil therapy, respectively.
Neutropenia, the most prevalent grade 3 or higher adverse event, was reported in 30%, 9%, and 41% of patients in acalabrutinib combination, acalabrutinib monotherapy, and chlorambucil combination cohorts, respectively.
Grade 3 or higher infections were most common among patients in the acalabrutinib combination cohort (21%), followed by acalabrutinib monotherapy (14%), and chlorambucil combination cohorts (8%).
Second primary malignancies, 55% of which were nonmelanoma skin cancers, were observed in 11%, 9%, and 8% of patients treated with acalabrutinib-obinutuzumab, acalabrutinib monotherapy, and obinutuzumab-chlorambucil, respectively.
All-cause mortality rates among acalabrutinib-obinutuzumab, acalabrutinib monotherapy, and obinutuzumab-chlorambucil groups were 4%, 7%, and 9%, respectively.
“In summary, in patients with treatment-naive [CLL], acalabrutinib with or without obinutuzumab improved progression-free survival over chemoimmunotherapy, and had a manageable safety profile, with 79% of patients remaining on therapy after a median follow-up of 28.3 months,” the investigators concluded. “The phase 3 ELEVATE-TN study substantiates that acalabrutinib with or without obinutuzumab is an efficacious and well tolerated treatment for patients with treatment-naive [CLL].”
Disclosure: This clinical trial was funded by Acerta Pharma, a member of the AstraZeneca Group. Please see the original reference for full list of authors’ disclosures.
Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291.