REAL-WORLD OUTCOMES OF PIRTOBRUTINIB IN RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA: A MULTICENTER ANALYSIS WITH A CONTROL COHORT FROM THE EUROPEAN MCL REGISTRY

E. Aydilek, F. Schwarz, and L. Simon equally contributing author.

Introduction: Pirtobrutinib (P), a highly selective, non-covalent BTK inhibitor (BTKi), has shown promising results in the BRUIN trial for relapsed/refractory mantle cell lymphoma (r/r MCL). However, there are limited data outside clinical trials, which would be helpful to understand the full impact of this novel approach. To address this knowledge gap, we analyzed real-world outcomes of patients treated with P with the named patient program in Germany and additional patients from the European Mantle Cell Lymphoma (EMCL) registry.

Methods: We identified 63 patients in the EMCL registry from Germany, Switzerland, Austria, and Portugal with r/r MCL who received P. Primary endpoints were treatment intent (bridging/definite) overall response rate (ORR), efficacy to bridge for consolidation with chimeric antigen receptor (CAR) T-cells and overall survival (OS). Survival outcomes were compared using the log-rank test for overall OS and chi-square test at appropriate follow-up times (FUT). Median FUT was estimated with the reverse KM method. A data cut-off as of 10.03.2025 was used, and updated results will be presented. In addition, results were compared to the results obtained with preceding BTKi-therapy.

Results: Median age at treatment start of P was 72 years (range: 45–86 y), with a median time since diagnosis of 5.75 years (range: 0.3–24 y). Patients were predominantly male (75.8%, 47/62 (result/number with available information)). At treatment initiation with P, clinical characteristics included ECOG ≥ 2 in 27% (13/48), Ki-67 ≥ 30% in 82% (18/22), blastoid or pleomorphic morphology in 37% (15/41), TP53 mutations in 60% (15/25) and 3 median lines of prior therapy (range: 1–11). 97% of patients (61/63) had prior ibrutinib (I) treatment, 37% (23/63) autologous transplantation, 8% (5/63) allogeneic transplantation or had receive prior CAR-T therapy 13% (8/63). The majority received P monotherapy (92%, 45/49). After a median FUT of 5.2 months (range: 0.2–30.4 month), 78% (49/63) showed no progression on P. OS probability was 50.1% at two years. P was used as bridging therapy before CAR-T in 49% (24/49) of cases. When comparing results of P with I without subsequent CAR-T therapy, we observed a comparable ORR (57.8% vs. 53.9%), with no significant differences in overall OS (p = 0.74) or at one or two years FUT (1-year: p = 0.9; 2-year: p = 0.16). However, in the group of patients without CAR-T-consolidation (n = 17) ORR tended to be lower 50% (7/14).

Conclusion: In this real-world cohort with adverse patient characteristics P was effective with a higher ORR (57.8% vs. 49.3%) and similar CR rates (17.7% vs. 15.8%) as in the BRUIN trial. Interestingly, in this preliminary analysis subsequent P therapy after prior I treatment did not result in a decrease in response and disease control. Utilization as bridging strategy to CAR-T therapy is feasible. Longer follow-up times are needed to assess response durability and long-term survival.

Research funding declaration: This research received no external funding.

Keywords: non-Hodgkin; cellular therapies; molecular targeted therapies

Potential sources of conflict of interest:

E. Aydilek

Consultant or advisory role: AstraZeneca

Honoraria: Kite/Gilead, Janssen and Lilly

E. Shumilov

Consultant or advisory role: Sanofi, Stemline, Amgen, Takeda, Pfizer, BMS, Oncopeptides

Honoraria: Amgen, Sanofi, Stemline, BMS, Incyte, Takeda, Pfizer, Oncopeptides, Lilly

G. Lenz

Honoraria: ADC Therapeutics, AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Constellation, Genase, Genmab, Gilead, Hexal/Sandoz, Immagene, Incyte, Janssen, Karyopharm, Lilly, Miltenyi, MorphoSys, MSD, NanoString, Novartis, PentixaPharm, Pierre Fabre, F. Hoffmann-La Roche Ltd, and Sobi

Other remuneration: research grants from AGIOS, AQUINOX, AstraZeneca, Bayer, Celgene, Gilead, Janssen, MorphoSys, Novartis, F. Hoffmann-La Roche Ltd, and Verastem

C. Pott

Honoraria: Roche, Lilly, Novartis, Kite Gilead

M. Tometten

Honoraria: Honoria from Hexal, Merck, Incyte, MSD

S. Stilgenbauer

Other remuneration: Advisory board honoraria, Research support, Travel support and Speaker fees from AbbVie, Amgen, AstraZeneca, BeiGene, BMS, Galapagos, Gilead, GSK, Hoffmann-La Roche, Johnson & Johnson, Lilly, Novartis, Sunesis

M. Gomes da Silva

Consultant or advisory role: Roche, Janssen, Lilly, Beigene

Educational grants: Janssen, Gilead, Abbvie

Other remuneration: Research grant: AstraZeneca