Dr Koff on Toxicities Associated With Pirtobrutinib in MCL

Jean L. Koff, MD, MS, associate professor, Department of Hematology and Medical Oncology; clinical investigator, Bone Marrow and Stem Cell Transplant Center, Emory University School of Medicine; member, Discovery and Developmental Therapeutics Research Program, Winship Cancer Institute, Emory University, discusses 

 (Jaypirca) in patients with mantle cell lymphoma (MCL).

FDA approved pirtobrutinib for the treatment of adult patients with relapsed/refractory

 who have undergone at least 2 lines of systemic therapy, including a BTK inhibitor, Koff begins. This approval was granted under the FDA's accelerated approval pathway and was supported by data from the phase 1/2 BRUIN trial (NCT03740529), which was an open-label, single-arm study, she explains. In BRUIN, pirtobrutinib elicited an overall response rate of 50% (95% CI, 41%-59%) in patients who received the agent at a daily dose of 200 mg once daily (n = 120) and a complete response rate of 13%, as well as a partial response rate of 38%.

During the BRUIN trial, pirtobrutinib was primarily associated with constitutional symptoms, such as fatigue, along with gastrointestinal adverse effects (AEs), such as diarrhea, Koff continues. These AEs were generally manageable, she says, adding that as with other BTK inhibitors, infections were observed, which is common among patients undergoing lymphoma treatment. However, the incidence of severe infections specifically attributable to pirtobrutinib was low, she notes. Bruising was noted among the patients, but no cases of severe bruising or hemorrhage were reported, Koff reports.

Atrial fibrillation or flutter, which can be a concern with BTK inhibitors, occurred at a very low rate with pirtobrutinib, she expands. Similarly, hypertension is another AE that requires monitoring in patients receiving BTK inhibitors, Koff states, adding that the incidence of pirtobrutinib-related hypertension was very low, with no instances of severe-grade high blood pressure. Community oncologists should be aware of these potential AEs when considering pirtobrutinib for their patients but can be reassured by the relatively low incidence of severe AEs, she concludes.

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Jean L. Koff, MD, MS, discusses the toxicities associated with pirtobrutinib in the BRUIN trial for mantle cell lymphoma.

Dr Koff on the Safety Profile of Pirtobrutinib in Pretreated CLL/SLL

Jean L. Koff, MD, MS, associate professor, Department of Hematology and Medical Oncology; clinical investigator, Bone Marrow and Stem Cell Transplant Center, Emory University School of Medicine; member, Discovery and Developmental Therapeutics Research Program, Winship Cancer Institute, Emory University, discusses the safety profile of pirtobrutinib (Jaypirca) according to data from the phase 1/2 BRUIN trial (NCT03740529) in chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The FDA granted accelerated approval to pirtobrutinib

 in December 2023 for the treatment of adult patients with CLL or SLL who previously received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. This regulatory decision was supported by updated findings from the phase 1/2 BRUIN trial (NCT03740529).

In the BRUIN trial, pirtobrutinib demonstrated favorable tolerability, Koff begins. The most commonly observed adverse effects (AEs) were constitutional symptoms such as fatigue, Koff reports. Diarrhea occurred in 28.4% of patients at a generally low grade and cough was reported in 27.3% of patients, she adds. Similar to other covalent BTK inhibitors, bruising and bleeding events were noted with pirtobrutinib; these were typically mild, Koff notes.

Other AEs of interest with BTK inhibitors, such as hypertension, were observed infrequently in the CLL cohort, Koff continues. The incidence of treatment-related hypertension was 3.5%, and few grade 3 or higher events (0.4%) were reported, she says, adding that the rates of treatment-related atrial fibrillation and flutter were also low at 1.4%. Neutropenia emerged as a notable cytopenia associated with pirtobrutinib, occurring in 28.4% of patients with CLL/SLL as a grade 3 or higher AE, Koff states. This AE is commonly observed when administering the majority of lymphoma-directed therapies, she notes.

These findings underscore pirtobrutinib's manageable safety profile in this heavily pretreated population, Koff emphasizes. Overall, the approval of pirtobrutinib represents a significant advancement in treatment options for patients with CLL and SLL who have exhausted other therapeutic options, providing a new targeted treatment approach with encouraging tolerability and efficacy data from the BRUIN trial.

Jean L. Koff, MD, MS, discusses the safety profile of pirtobrutinib in pretreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Jean L. Koff, MD, MS, assistant professor, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, discusses systemic therapies in follicular lymphoma.

There are many treatment options for patients with newly diagnosed or relapsed/refractory follicular lymphoma, explains Koff. Patient-related factors such as disease burden and personal preference may help guide treatment selection.

For example, the combination of lenalidomide (Revlimid) and rituximab (Rituxan; R

) is approved for patients with previously treated follicular lymphoma and marginal zone lymphoma.

Additional research regarding proper sequencing and patient selection will provide insight on optimal treatment approaches, concludes Koff.

Jean L. Koff, MD, MS, discusses systemic therapies in follicular lymphoma.

Jean L. Koff, MD, MS

Articles

Dr Koff on Toxicities Associated With Pirtobrutinib in MCL

Dr Koff on the Safety Profile of Pirtobrutinib in Pretreated CLL/SLL

Dr. Koff on Systemic Therapy Options in Follicular Lymphoma