Objective: In the absence of head-to-head clinical trials, matching-adjusted indirect comparison (MAIC) was used to compare two Bruton tyrosine kinase inhibitors (BTKis) approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). This analysis compares the efficacy and safety of acalabrutinib versus ibrutinib using a more mature dataset than a previously published MAIC.
Methods: Individual patient data from 122 patients treated with acalabrutinib in a phase 2 study were weighted to match aggregate baseline characteristics of patients pooled from three separate trials of ibrutinib. Patients were matched on Eastern Cooperative Oncology Group performance status, simplified Mantle Cell Lymphoma International Prognostic Index, lactate dehydrogenase, prior lines of therapy, tumor burden, and blastoid histology. Outcomes assessed included progression-free survival (PFS), overall survival (OS), and adverse events.
Results: After matching, differences in PFS between acalabrutinib (median = 17.8 months) and ibrutinib (median = 12.8 months) were not statistically significant (hazard ratio [HR] = 0.92; 95% confidence interval [CI] = 0.74-1.15; p = 0.48). Similarly, after matching, OS differences between acalabrutinib (median = 36.5 months) and ibrutinib (median = 27.9 months) did not reach statistical significance (HR = 0.87; 95% CI = 0.64-1.17; p = 0.35). Acalabrutinib was associated with an improved safety profile compared with ibrutinib, with statistically significantly lower rates of grade ≥3 atrial fibrillation and thrombocytopenia.
Conclusions: This comparison of two BTKis used in the treatment of R/R MCL showed that PFS and OS risk was not statistically different between the treatments; however, acalabrutinib had an improved safety profile compared with ibrutinib.
Keywords: C; C00; C1; C10; I; I1; I10; Mantle-cell lymphoma; acalabrutinib; ibrutinib; matched-pair analysis; non-Hodgkin lymphoma.
Mantle cell lymphoma (MCL) is an aggressive and rare type of cancer that affects lymphoid cells and often returns after previously responding to treatment (relapsed) or stops responding to treatment (refractory). Acalabrutinib and ibrutinib belong to a class of drugs referred to as Bruton tyrosine kinase inhibitors and are approved for the treatment of relapsed or refractory MCL. There is currently no direct head-to-head trial available to compare the efficacy and safety of acalabrutinib and ibrutinib in patients with relapsed or refractory MCL. To compare these drugs, the authors used a method referred to as a matching-adjusted indirect comparison (MAIC), which allows for comparison of the efficacy and safety of acalabrutinib versus ibrutinib using data from different clinical trials. This MAIC study found that there were no statistically significant differences in survival outcomes in patients with relapsed or refractory MCL who were treated with either acalabrutinib or ibrutinib. However, acalabrutinib was associated with an improved safety profile compared with ibrutinib. When there are many treatment options available for patients, knowing how different treatments compare in terms of efficacy and safety may help patients and physicians choose the most appropriate therapy. Although direct comparisons are the most accurate way to compare different treatments, when they are unavailable, MAIC studies can help patients and healthcare providers in the decision-making process.