Favorable clinical outcomes in patients with refractory or relapsed CLL/SLL

December 2022 Clinical practice Nalinee Pathak

CHRONIC MYLELOGENOUS LEUKEMIA (also called MYELOGENOUS LEUKEMIA), many MYELOBLASTS (Immature white blood cells or leukocytes), 250X. This is a human blood smear showing numerous Myeloblasts (immature white blood cells or leukocytes). It also shows an Eosinophil with reddish granules and a bilobed nucleus, and a BAND CELL (near the center, has a horseshoe-shaped nucleus) that develops into a NEUTROPHIL (the most common white blood cell). Large numbers of these is considered abnormal. These cells originate in the red bone marrow (MYELOID tissue), hence the name Myelogenous. Leukemia is a cancer of the blood forming tissues, and involves an abnormal proliferation of white blood, cells (leukocytes), many of which are immature, and do not perform normal functions. This great increase in leukocytes can also crowd out red blood cells and platelets. This image also shows numerous, smaller red blood cells (erythrocytes).

Zanubrutinib (marketed by BeiGene under the brand name Brukinsa) extends progression-free survival (PFS) in patients with relapsed or refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma (CLL/SLL).

Bruton’s tyrosine kinase (BTK) inhibitors effectively treat CLL and SLL. The ALPINE study has evaluated the efficacy of BTK’s selective inhibitor, zanubrutinib, versus ibrutinib.

Study Design

Between November 2018 to December 2020, the open-label ALPINE study recruited 652 patients with relapsed or refractory CLL or SLL who had received at least one prior line of therapy. 45% of these patients had bulky disease, with 23% having 17p deletion, TP53 mutation or both. Most patients were white (81%) with a median age of 67 years. The participants were randomised (1:1) to receive either zanubrutinib or ibrutinib.

Main Findings

After a median follow-up of 29.6 months, disease progression was seen in fewer patients (87) after zanubrutinib treatment as compared to the ibrutinib arm (118, HR 0.65, 95% CI 0.49-0.86, P=0.002). Further, the progression-free survival (PFS) was higher with zanubrutinib vs ibrutinib (78.4% vs 65.9%). A similar situation was observed in the highest-risk group of 17p deletion, a TP53 mutation, or both with zanubrutinib (24 and 36 occurrences of disease progression or death; HR 0.53, 95% CI 0.31-0.88).

The overall response rate was also higher in the zanubrutinib arm compared to the ibrutinib treatment (86.2% vs 75.7%).

Fewer treatment-related adverse events (AEs) with zanubrutinib (42% vs 50%), dose interruptions (50% vs 56.8%), and discontinuation of treatment (15.4% vs 22.2%) were observed.