An indirect comparison of acalabrutinib with and without obinutuzumab versus zanubrutinib in treatment-naive CLL

• Versus zanubrutinib, acalabrutinib plus obinutuzumab had longer INV-PFS whereas acalabrutinib monotherapy showed no difference.

• The odds of having hypertension were significantly lower with acalabrutinib monotherapy versus zanubrutinib.

The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy versus zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data (IPD) from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. Post-matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR]: 0.41; 95% CI: 0.23-0.74) and comparable with acalabrutinib monotherapy (HR: 0.91; 95% CI: 0.53-1.56) versus zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension versus zanubrutinib (OR: 0.44, 95% CI: 0.20-0.99), while acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (odds ratio [OR]: 2.19; 95% CI: 1.33-3.60) and arthralgia (OR: 2.33; 95% CI: 1.37-3.96) versus zanubrutinib. No other significant differences in safety were observed. In summary, compared with zanubrutinib, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension.