Dr Islam on the Current and Expanding Role of Pirtobrutinib in MCL

Prioty Islam, MD, MSc, attending physician, medical oncologist, Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, discusses how the approval of the noncovalent BTK inhibitor pirtobrutinib (Jaypirca) has transformed the treatment of patients with mantle cell lymphoma (MCL), and where this agent fits in to the current treatment armamentarium.

Pirtobrutinib received FDA approval in January, 2023, for the treatment of patients with relapsed/refractory MCL who have been previously exposed to at least 2 prior lines of systemic therapy, including a BTK inhibitor. This approval was supported by data from the phase 1/2 BRUIN trial (NCT03740529), in which a subset of patients with MCL achieved a high overall response rate (ORR) with the agent.

Historically, patients with relapsed/refractory MCL experienced poor prognosis and did not respond well to chemoimmunotherapy regimens, Islam begins. However, the introduction of single-agent, oral targeted BTK inhibitors, such as pirtobrutinib, to the treatment armamentarium has improved the durability of patient responses to treatment, Islam states, as well as patients' quality of life. Accordingly, this drug class has significantly affected the treatment of relapsed/refractory MCL, she says.

Much like its activity in chronic lymphocytic leukemia, pirtobrutinib has been shown to successfully restore BTK inhibitor dependency in patients with MCL, as well as induce responses in those who previously progressed on a different BTK inhibitor, Islam continues. Although there is interest in moving pirtobrutinib into earlier lines of therapy in MCL, efforts to accomplish this remain both a challenge and a subject of debate due to a lack of data on patient responses after progression on pirtobrutinib, Islam cautions. 

The ongoing, randomized phase 3 BRUIN-MCL-321 trial (NCT04662255) is investigating pirtobrutinib vs investigator’s choice of BTK inhibitor in patients with pretreated, BTK inhibitor–naïve MCL. Findings from the trial are hoped to illuminate the feasibility of utilizing pirtobrutinib in the frontline, as the current FDA indication for this agent is after progression on or intolerance to a prior covalent BTK inhibitor, Islam says.

Disclosures: Dr Islam reports consulting roles with AbbVie, AstraZeneca, BeiGene, DAVA Oncology, and LOXO Oncology; as well as speaking roles with Targeted Oncology and The Video Journal of Hematologic Oncology (VJHemOnc).

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