Pirtobrutinib in Patients with Mantle Cell Lymphoma: A Real-World Study in the United States

Introduction

Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi) that has demonstrated promising efficacy and safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). Pirtobrutinib was approved in the United States for patients with MCL after at least two lines of systemic therapy, including a BTKi, on January 27, 2023, based on data from the BRUIN-18001 Phase 1/2 study. Since the time of this approval, there has been limited real-world data on pirtobrutinib use. This study described characteristics and treatment patterns of patients with MCL who received pirtobrutinib treatment within 15 months after approval in the United States.

Methods

This observational study used the nationwide Flatiron Health electronic health record-derived de-identified database of patients with MCL. Patients with available line of therapy data who initiated pirtobrutinib between January 27, 2023, and April 30, 2024, were included. Descriptive statistics were used to summarize demographic, clinical, and treatment pattern data.

Results

Of 82 eligible patients, the majority were male (n=57; 69.5%) and treated in community practice settings (n=51; 63.8%). Patients' median age was 75 years (IQR: 65, 79), median time from diagnosis to initiation of pirtobrutinib was 54.9 months (IQR: 32.7, 94.8), and median follow up time from initiation of pirtobrutinib was 5.4 months (IQR: 2.5, 8.3). Among patients with available data, 24.2% (n=16 of 66) had an ECOG performance status of 2+, 60.8% (n=31 of 51) had Ki-67 index of 30% or more, and 8.5% (n=7) had blastoid or pleomorphic disease. Most received pirtobrutinib as monotherapy (n=62; 75.6%) while the remainder received combination therapy. Median line of therapy of initial pirtobrutinib use was 4 (IQR: 3, 5) with 64.6% (n=53) of patients initiating pirtobrutinib in the 3^rd/4^th line setting and 19.5% (n=16) receiving it in the 6^th line or later. In their treatment history, nearly all patients had received a prior covalent BTKi (cBTKi) (n=77; 93.9%), and 9.8% (n=8) had prior CAR-T therapy. Immediately prior to receiving pirtobrutinib, 34.1% (n=28) of patients were treated with cBTKi monotherapy, 28.0% (n=23) received a cBTKi combination regimen, and 8.5% (n=7) had CAR-T therapy. Among patients who discontinued their initial pirtobrutinib regimen (n=37; 45.1%), CAR-T therapy was the most common treatment received immediately following pirtobrutinib (n=9 of 37; 24.3%). Eight of 37 (21.6%) patients received pirtobrutinib in the subsequent line of treatment after discontinuing their initial pirtobrutinib, either as re-challenge or in combination through addition of another drug to the regimen (which per Flatiron Health rules advances the line of therapy).

Conclusions

In this initial post-approval time frame, the majority of patients with MCL initiated pirtobrutinib as monotherapy and consistent with its labeled indication in the post-cBTKi setting. Patients in the real-world reflected a more heterogeneous population including older patients with poorer performance status than those commonly enrolled in clinical trials. The observed treatment patterns demonstrated how pirtobrutinib appears to be used in routine clinical practice.

Shah:Gilead-Kite, BMS-Juno, Miltenyi, Lilly Onclogy, Novartis, Seattle Genetics, Janssen, Abbvie, Cargo, Beigene, Galapagos, AstraZeneca: Honoraria; Tundra Therapeutics: Current holder of stock options in a privately-held company; Miltenyi Biomedicine, Lilly Oncology: Research Funding. Winfree:Eli Lilly and Company: Current Employment, Current equity holder in publicly-traded company. Bhandari:Eli Lilly and Company: Current Employment, Current equity holder in publicly-traded company. Ma:Eli Lilly and Company: Current Employment. He:Eli Lilly and Company: Consultancy. Abhyankar:Eli Lilly and Company: Current Employment. Hess:Eli Lilly and Company: Current Employment.

Pirtobrutinib is approved for use as monotherapy. In real-world clinical practice, as reported in our abstract, some use in combination with other regimens is documented.