Chronic Lymphocytic Leukemia (CLL)

In this video, Prof EM Dominique Bron, haematologist at the Jules Bordet Institute in Brussels provides us with a helicopter view of the contemporary treatment landscape for patients with chronic lymphocytic leukemia (CLL) and summarizes some of the key results in the field of CLL presented during the 2024 annual EHA meeting.

Anno 2024, the treatment for patients with CLL is no longer steered by the fitness of the patients, but rather by the presence or absence of a del(17p), or TP53 mutation. In patients without this dismal prognostic feature, the current standard of care consists of a fixed duration treatment combination of either venetoclax + ibrutinib, or venetoclax + obinutuzumab. With these regimens, a median progression-free survival (PFS) of ≥80 months can be achieved, with MRD negativity in about 50% of patients.

In patients with a TP53 mutation, there is consensus on the fact that a BTK inhibitor should be part of the first line treatment, either as a fixed duration combination of ibrutinib with venetoclax or as continuous therapy with a next-generation BTK inhibitor, such as acalabrutinib, or zanubrutinib. While significant progress has been made in the treatment of these patients, their prognosis continues to be inferior to that of patients without a TP53 mutation, indicating that there is still room for improvement. In this respect, data from arm D of the SEQUOIA trial, presented at EHA 2024 demonstrated impressive results with a combination of zanubrutinib and venetoclax.¹ In a cohort of 66 treatment-naïve CLL patients with a TP53 mutation, this combination led to an objective response rate (ORR) of 100%, including 45% complete responses (CR). Furthermore, MRD negativity was obtained in 50% of patients, with a 2-year PFS rate of 94%.¹

A second interesting study presented at EHA 2024 evaluated the safety and efficacy of the bispecific antibody epcoritamab in CLL patients with Richter’s transformation (RT), a notoriously difficult to treat patient population. Of the 35 patients enrolled in this study, 91% received at least 1 prior line of therapy for CLL or RT, including a BTK inhibitor in 57%. Of the patients who were pre-treated for RT, 76% received R-CHOP. The primary results of this study showed an ORR of 62%, with a CR in 35% of patients.²

A final presentation that was discussed by Prof Bron consists of a phase II study evaluating a triplet combination of the non-covalent BTK inhibitor pirtobrutinib, with venetoclax and obinutuzumab.³ The study enrolled a total of 40 treatment-naïve CLL patients, of whom 10% had a del(17p)/TP53 mutation. The first results with this triplet regimen are impressive, with an MRD negativity rate of 76%. More mature data are eagerly awaited.