December 11, 2023
By Catlin Nalley
Findings from the 6-year follow-up of the ELEVATE-TN study demonstrated that the safety and efficacy of acalabrutinib with or without obinutuzumab was maintained among patients with treatment-naïve chronic lymphocytic leukemia, including those with high-risk genetic features.
This data was recently presented by study author Jeff Sharman, MD, Director of Research at the Willamette Valley Cancer Institute and Research Center/US Oncology Research, during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 9-12 in San Diego (Abstract 636).
“Acalabrutinib is a BTK inhibitor approved for the treatment of CLL/SLL and relapsed mantle cell lymphoma,” noted Sharman. “The initial report of Elevate-TN occurred when study subjects had a median follow-up of 28 months. That report demonstrated the superiority of acalabrutinib therapy over chemoimmunotherapy and led to the approval of the regimens in previously untreated chronic lymphocytic leukemia.
“Subsequent presentations with a median follow-up of 4 and 5 years have been previously reported,” he continued. “This presentation evaluates the data at approximately 6 years of follow-up with several new analyses particularly focused on the impact of adding obinutuzumab to acalabrutinib, a question that has been important for the field.”
Research Highlights
In this prospective, three-arm, randomized study, patients with treatment-naïve chronic lymphocytic leukemia received acalabrutinib plus obinutuzumab (n=179), acalabrutinib monotherapy (n=179), or obinutuzumab plus chlorambucil (n=177). Patients who progressed on obinutuzumab plus chlorambucil had the option to crossover to acalabrutinib monotherapy. At 6 years, approximately half of the patients assigned to acalabrutinib regimens remain on therapy, according to Sharman, who noted that the obinutuzumab plus chlorambucil arm was fixed duration.
Data showed a significantly higher progression-free survival for acalabrutinib-containing arms when compared with obinutuzumab plus chlorambucil. Median progression-free survival was not reached in both acalabrutinib regimens versus 27.8 months for obinutuzumab plus chlorambucil.
Sharman reported that acalabrutinib in combination and alone led to significantly higher overall and complete response rates. Additionally, he noted that patients who received acalabrutinib and experienced CR/complete remission with incomplete count recovery (CRi) had longer progression-free survival.
Among patients in the crossover population, the median PFS2—time to second disease progression or death—was not reached. The estimated 72-month PFS2 rate was 54 percent. The median overall survival was not reached in any treatment arm; however, it was longer with acalabrutinib plus obinutuzumab versus obinutuzumab plus chlorambucil. Estimated 72-month overall survival rates were 87 percent for acalabrutinib plus obinutuzumab, 79 percent for acalabrutinib monotherapy, and 80 percent for obinutuzumab plus chlorambucil.
When discussing safety, Sharman noted that adverse events of clinical interest were similar in both acalabrutinib-containing cohorts and consistent with previous results. No differences were observed between the two acalabrutinib arms for major bleeding, infections, or second primary malignancies, he reported, while also highlighting that the incidence of cardiac-related adverse events remained low throughout the study.
Common Grade 3 or higher adverse events in the acalabrutinib plus obinutuzumab and acalabrutinib monotherapy arms included neutropenia, thrombocytopenia, diarrhea, COVID-19, pneumonia, syncope, and hypertension.
“In conclusion, acalabrutinib-containing regimens led to improve progression-free survival over obinutuzumab plus chlorambucil,” Sharman noted. “The addition of obinutuzumab to acalabrutinib resulted in improved response rates and progression-free survival compared to acalabrutinib monotherapy.
“Obtaining complete response with acalabrutinib-containing regimens leads to improved progression-free survival, and the safety of acalabrutinib regimens in treatment-naive chronic lymphocytic leukemia remains consistent with prior reports,” he reiterated.
Catlin Nalley is a contributing writer.