Wojciech Jurczak, MD, PhD

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, 

 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, 

 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.

 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.

 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.

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Wojciech Jurczak, MD, PhD, discusses the available treatment options for patients with relapsed/refractory chronic lymphocytic leukemia who relapsed on BCL2 inhibitors.

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, discussed the results of the clinical trial investigation of ceralasertib (AZD6738) with or without acalabrutinib (Calquence) in patients with high-risk relapsed/refractory chronic lymphocytic leukemia (R/R CLL).

The phase 1/2 study (NCT03328273) investigated the ATR inhibitor ceralasertib in patients with R/R CLL who had a 17p deletion, 

 mutation, or 11q deletion. The study had 2 cohorts, 1 received ceralasertib monotherapy and the other, which only included patients with 11q deletions, received combination ceralasertib plus acalabrutinib.

However, the monotherapy arm was discontinued due to dose-limiting hematologic toxicities, and no patients in this arm appeared to benefit from ceralasertib. Some partial responses (PRs) were observed in the combination therapy arm. There were no complete responses (CRs) in either arm.

Jurczak says that although the study did not have positive results as a whole, ceralasertib may have a role in patients with 11q deletions based on the results of the combination cohort, though it would need to be explored further as the cohort was not large. The ATR inhibitor would likely not be a good option in the first 2 lines of therapy but could be used in patients with 11q deletions whose disease progresses on BTK (Bruton tyrosine kinase) or BCL-2 inhibitors, according to Jurczsk.

 Throughout this study, we could not achieve any CRs. The only PRs we observed were in arm B, where it was acalabrutinib plus ceralasertib with 11q deletion. All the other patients either progressed, or we could observe just stabilization of the process. Therefore, as a conclusion, ceralasertib as a monotherapy was not recommended, and a combination therapy was potentially effective in the patients with 11q deletion, although the study didn't recruit well enough to find enough patients make the results meaningful.

The mechanism of action is unique, and it could be further explored in patients with 11q deletion, although I would rather not recommend it in the first 2 lines of therapy. In those with 11q deletion failing a more dedicated therapy like BTK inhibitors including pirtobrutinib, or BCL-2 inhibitors, it could be a reasonable option, and it could be further investigated in this cohort.

Articles

Wojciech Jurczak, MD, PhD, discussed the results of the clinical trial investigation of ceralasertib with or without acalabrutinib in patients with high-risk relapsed/refractory chronic lymphocytic leukemia.

Wojciech Jurczak, MD, PhD | Authors

Articles

Treatment Options After Relapse in CLL

Ceralasertib Shows Limited Efficacy in R/R CLL With 11q Deletions