BTK Inhibitor Acalabrutinib With or Without Obinutuzumab Demonstrated Improved Quality-Adjusted Survival Time Among Patients With Treatment-Naive CLL

Results from the Phase 3 ELEVATE-TN Trial
 

According to findings from the phase 3 ELEVATE-TN recently published in Leukemia & Lymphoma, acalabrutinib monotherapy, as well as the combination of acalabrutinib plus obinutuzumab, resulted in improved  quality-adjusted time without symptoms and toxicity among patients with treatment-naive chronic lymphocytic leukemia (CLL), compared with treatment with chlorambucil plus obinutuzumab.

Targeted therapy acalabrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor often used to treat hematologic malignancies like CLL and mantle cell lymphoma (MCL). Acalabrutinib works by specifically targeting and inhibiting BTK, an enzyme involved in the growth and survival of cancer cells. 

In this study, Jeff P Sharman, MD, Willamette Valley Cancer Institute and Research Center, Eugene, Oregon, and coauthors aimed to compare the efficacy and safety of acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, and chlorambucil plus obinutuzumab among patients with treatment-naive CLL. 

To assess the relative risk-benefit of treatment, the study authors utilized the Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) methodology. 534 patients with ages either ≥65 years or 18 to 64 years with comorbidities and treatment-naive CLL were included in this trial. Patients were randomly assigned to receive acalabrutinib monotherapy (n=179), acalabrutinib plus obinutuzumab (n=178), or chlorambucil plus obinutuzumab (n=177), all of which were administered in 28 day cycles. Patients were also split into 3 health states: time with toxicity (TOX), time without symptoms or toxicity (TWiST), and time after relapse (REL). The duration of each of these health states was calculated to reflect the impact on patients’ quality of life in each state. 

Results indicated that patients who received acalabrutinib monotherapy and patients who received acalabrutinib plus obinutuzumab had a significantly longer duration of TWiST (the mean difference being 13.42 months in the acalabrutinib monotherapy arm and 13.63 months in the acalabrutinib plus obinutuzumab arm) compared with the chlorambucil plus obinutuzumab arm. These patients also had a significantly shorter duration of REL and TOX compared with patients in the chlorambucil plus obinutuzumab arm. 

When toxicity was defined as grade 3 to 4 events, the mean Q-TWiST for patients who received acalabrutinib monotherapy and patients who received acalabrutinib plus obinutuzumab was 41.79 and 42.07 months, compared to 34.56 months among patients who received chlorambucil plus obinutuzumab. When toxicity was defined as grade 2 to 4 adverse events, the mean Q-TWiST for patients who received acalabrutinib monotherapy and patients who received acalabrutinib plus obinutuzumab was 35.07 and 34.21 months, compared to 30.64 months among patients who received chlorambucil plus obinutuzumab. 

“Treatment with acalabrutinib, as monotherapy or in combination with obinutuzumab, resulted in a statistically significant and clinically important improvement in quality-adjusted time without symptoms of disease progression and toxicity compared with chlorambucil plus obinutuzumab,” Dr Sharman and coauthors concluded. 

Source: 

Sharman JP, Miranda P, Roos J, et al. Quality-adjusted survival time without symptoms or toxicity of acalabrutinib with or without obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia. Leukemia & Lymphoma. Published online May 23, 2023:1-10. doi: 1080/10428194.2023.2212433