Assessing the Burden of Adverse Events in a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia (CLL)

Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus‐based position paper from an ad hoc expert panel

“… 43 The same median PFS was observed in patients included in the two treatment arms, 38.4 months. Compared to patients treated with ibrutinib, those who received acalabrutinib showed lower rates of atrial fibrillation/flutter events, 9.4% versus 15.6%, and hypertension, 15.8% versus 22.8%, while the infection rate was similar in the two arms, 28.9% versus 29.7% 44 . Treatment discontinuations due to AEs were recorded in 15% patients treated with acalabrutinib (Table 3).…”

“…Taking into account the clear superiority of BTK inhibitors compared to chemoimmunotherapy, in both front‐line 21,23–26,28–33 and advanced‐line 41,42,44,49 , trials, the latter is not anymore a treatment option for the large majority of TN and for R/R patients with CLL.…”

Approach to relapsed CLL including Richter Transformation

“…The newer more selective covalent BTKis acalabrutinib and zanubrutinib have both been compared directly against ibrutinib with each demonstrating advantages (Table 2). The ELEVATE R/R study 38 with acalabrutinib showed non‐inferior PFS to ibrutinib (consistent in all biological subsets) but a clearly superior toxicity profile with lower rates of atrial arrhythmias, hypertension and cumulatively a lower cumulative toxicity burden 48 . The ALPINE study compared zanubrutinib to ibrutinib and also displayed superior tolerability, fewer discontinuations and a lower rate of arrhythmias, but no difference in rates of hypertension (all grade; 21.9 vs. 19.8% and grade 3; 14.8 vs. 11.1%) 39 .…”

“…The ELEVATE R/R study 38 with acalabrutinib showed non-inferior PFS to ibrutinib (consistent in all biological subsets) but a clearly superior toxicity profile with lower rates of atrial arrhythmias, hypertension and cumulatively a lower cumulative toxicity burden. 48 The ALPINE study compared zanubrutinib to ibrutinib and also displayed superior tolerability, fewer discontinuations and a lower rate of arrhythmias, but no difference in rates of hypertension (all grade; 21.9 vs. 19.8% and grade 3; 14.8 vs. 11.1%). 39 A potential major advantage for zanubrutinib is that it also achieved statistically significantly superior PFS over ibrutinib (24 month rates of 79.5% vs. 67.3%; HR 0.65, p = 0.0024), but the PFS difference may in part be attributable to a relative "under performance" of ibrutinib in ALPINE relative to RESONATE and ELEVATE R/R.…”

Marginal zone lymphoma: 2023 update on diagnosis and management

“…As a result of the negative phase III study, the MZL indication for ibrutinib has been voluntarily withdrawn. While it can be used off‐label, zanubrutinib or acalabrutinib is preferred due to their comparatively more favorable safety profiles 117,118 …”