Treatment Options After Relapse in CLL

Wojciech Jurczak, MD, PhD, head of the department of oncology at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, discusses the available treatment options for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) who relapsed on BCL2 inhibitors.

Guidelines in the United States and in Europe differ for these patients, according to Jurczak. He discusses the differences between the 2 and how burton tyrosine kinase (BTK) inhibitors, such as venetoclax (venclexta), play a role in these patients’ treatment. Moreover, he discusses research into targeted agents in this next line of treatment.

This research included a phase 1/2 study (NCT03328273) that looked at the ATR inhibitor ceralasertib (AZD6738) in patients with R/R CLL who had a 17p deletion, TP53 mutation, or 11q deletion. There were 2 cohorts in the study, including 1 receiving ceralasertib monotherapy and only including patients with 11q deletion, combining ceralsertib and acalabrutinib (Calquence). However, the study showed that ceralasertib had a limited efficacy in this patient population.

The monotherapy arm was discontinued due to dose-limiting hematologic toxicities and no patients appeared to benefit from ceralasertib. Yet, Jurczak discussed that the ATR inhibitor can play a role in patients with 11q deletions due to the promising results of the combination cohort. However, it needs to be explored further.

Transcription:

0:07 | There is a tendency to offer the targeted therapy, namely the BTK inhibitors [such as] venetoclax, to everyone, while in Europe we are more conservative. The European guidelines make it compulsory to offer targeted therapy, molecular targeted therapy, to all patients with 17p deletion, p53 mutation, [and others] including 11q deletion, but we don't do not have to it is just a possibility. So still, some of the patients get chemoimmunotherapy, while some get targeted chemo or therapy with targeted agents.

0:57 | I'm [researching] therapy with targeted agents, and again, the question whether we want to go for BTK inhibitor monotherapy or a time limited therapy, which is offered by BCL2 inhibitors. We're not talking just about the things which aren't registered, because in clinical studies we are now investigating the combinations, or even triplets, of molecular targeted drugs and why both BCL2 inhibitors and BTK inhibitors are in fact given together.