Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphomas, Clinical Research, Diseases, indolent lymphoma, Lymphoid Malignancies
Methods: Pts with previously treated B-cell malignancies, including MZL, were eligible for pirtobrutinib monotherapy treatment in either the dose escalation or expansion portion of the multicenter, phase 1/2 BRUIN study. MZL diagnosis required local pathologic review of an adequate biopsy. Endpoints include overall response rate (ORR) assessed by investigator per Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A 05 May 2023 data cut was used.
Results: Among the 36 pts with MZL, 34 (94%) received the recommended phase 2 dose of pirtobrutinib, 200mg once daily. Pts had a median age of 68 (range 22-83), a majority were female (56%, n=20), and median prior lines of systemic therapy were 3 (range 1-10). Pts had nodal (47%, n=17), splenic (36%, n=13), and extranodal (17%, n=6) MZL subtypes. Most pts had Ann Arbor stage III/IV disease (81%, n=29). Most pts were in high risk MALT-IPI group (53%, n=19), 10 (28%) were intermediate, 1 (3%) was low, and missing in 6 (17%) pts. Baseline LDH was elevated in 15 (42%) pts and hemoglobin was <12 g/dL in 29 (81%) pts. All 36 MZL pts were previously treated with an anti-CD20 antibody, and 31 (86%) pts had received prior chemotherapy. Of the 26 pts (72%) with MZL who received a prior cBTKi, 20 (77%) pts discontinued due to progressive disease (PD) and 6 (23%) discontinued due to toxicity/other. Median time on treatment was 9 months (range 1.1-40.8), with 15 (47.1%) pts still receiving pirtobrutinib.
The ORR of the MZL cohort was 50% (95% confidence interval [CI], 32.9- 67.1), including 1 (2.8%) complete response, 17 (47.2%) partial responses (Figure). There were 15 (41.7%) pts with stable disease. The ORR in pts with nodal, splenic, and extranodal MZL were 58.8% (95%CI, 32.9-81.6), 30.8% (95%CI, 9.1-61.4), and 66.7% (95%CI, 22.3-95.7), respectively. The ORR for MZL pts with prior cBTKi therapy was 46.2% (95%CI, 26.6-66.6). With a median follow-up time of 17.6 months, median DOR was 12.7 months (95%CI, 5.6-non-estimable [NE]). Median PFS was 16.5 months (95%CI, 7.43-22.1) with a median follow up of 15.8 months. With a median follow up of 21.5 months, the median OS was NE (95%CI, 27.6-NE) and the 24-mo OS rate was 77.5% (95%CI, 56.3-89.3).
In the MZL cohort, the most frequent treatment-emergent adverse events (TEAE) of any grade regardless of attribution were diarrhea (36.1%, n=13), fatigue (33.3%, n=12), and contusion (30.6%, n=11). Grade ≥3 hemorrhage/hematoma was not observed, and any grade hypertension (5.6%, n=2) was infrequent. No atrial fibrillation/flutter was observed. The most frequent grade ≥3 TEAE was neutropenia/neutrophil count decreased (27.8%, n=10) and anemia (13.9%, n=5). Treatment-related AE led to dose reductions in 4 pts (11.1%) and pirtobrutinib discontinuation in 2 (5.6%) pts (diarrhea and platelet count decreased/neutropenia). No fatal TEAEs were observed.
Conclusions: In this cohort of heavily pre-treated R/R MZL pts, pirtobrutinib showed preliminary efficacy and was well tolerated with low rates of discontinuation. Pirtobrutinib appears to be a promising therapeutic option after cBTKi treatment in R/R MZL pts.
Disclosures: Patel: Fate Therapeutics: Research Funding; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Epizyme: Consultancy, Research Funding; Curis, Inc: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Sunesis Pharmaceuticals: Research Funding; Kite: Consultancy, Research Funding, Speakers Bureau; Loxo Oncology: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; CRISPR Therapeutics: Research Funding; Xencor: Consultancy, Research Funding; Caribou Biosciences: Consultancy; Morphosys: Consultancy; Nurix: Research Funding; MEI Pharma: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Trillium Therapeutics/Pfizer: Consultancy, Research Funding; TG Therapeutics: Consultancy, Speakers Bureau; BeiGene: Consultancy; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Research Funding; Abbvie: Consultancy. Vose: Eli Lilly and Company; Epizyme, Kite, Loxo, Novartis: Research Funding; AbbVie, MEI Pharma: Consultancy. Brown: Acerta/Astra-Zeneca: Consultancy; AbbVie: Consultancy; Alloplex Biotherapeutics: Consultancy; Gilead: Research Funding; MEI Pharma: Research Funding; Hutchmed: Consultancy; Pharmacyclics: Consultancy; Grifols Worldwide Operations: Consultancy; TG Therapeutics: Research Funding; SecuraBio: Research Funding; Beigene: Consultancy, Research Funding; Genentech/Roche: Consultancy; Kite: Consultancy; Numab Therapeutics: Consultancy; Merck: Consultancy; Pfizer: Consultancy; iOnctura: Consultancy, Research Funding; Loxo@Lilly: Consultancy, Research Funding. Maddocks: Incyte: Consultancy, Honoraria; BMS: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy; Genentech: Consultancy; GenMab: Consultancy; Janssen: Consultancy, Honoraria; Morphosys: Consultancy; Pharmacyclics: Consultancy, Research Funding; Gilead/Kite: Consultancy; BeiGene: Consultancy; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Eli Lilly and Company: Consultancy; Seattle Genetics: Consultancy; Novartis: Research Funding; Merck: Research Funding. Woyach: AbbVie Inc, Karyopharm Therapeutics, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, MingSight Pharmaceuticals, MorphoSys, Schrödinger, Verastem Inc.: Other: Contracted Research; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Genentech, a member of the Roche Group, Janssen Biotech Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Newave Pharmaceutical Inc, Pharmacyclics LLC, an AbbVie: Other: Advisory Committee and Consulting Agreements. Shah: Janssen: Consultancy; Epizyme: Consultancy; LOXO-Lilly: Consultancy, Other: Travel support; Tundra Therapeutics: Current holder of stock options in a privately-held company; BMS/Juno: Consultancy; Novartis: Consultancy; TG therapeutic: Consultancy; Umoja: Consultancy; Seattle Genetics: Consultancy; Gilead/Kite: Consultancy; Incyte: Consultancy; Abbvie: Consultancy; Lilly Oncology: Consultancy, Research Funding; Miltenyi Biotec: Consultancy, Other: Travel support, Research Funding. Fakhri: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS/Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab/Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; LOXO/Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Tessoulin: Gilead: Honoraria; Abbvie: Honoraria; Incyte: Honoraria; Kite: Honoraria. Ma: Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly and Company/Loxo Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Consultancy. Jagadeesh: Regeneron Pharmaceuticals: Research Funding; Debio Pharma: Research Funding; ATARA Biotherapeutics: Research Funding; MEI Pharma: Research Funding; LOXO Pharmaceuticals: Research Funding; AstraZeneca: Research Funding; Seagen: Research Funding; Trillium Pharmaceuticals: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Coombs: AbbVie, Genentech, Beigene, AstraZeneca, Lilly, Octapharma: Consultancy. Patel: Janssen Oncology: Honoraria; ION Pharmaceuticals: Other: Leadership; Olema Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Rhodes: ADC Therapeutics: Consultancy; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy; AstraZeneca: Consultancy; Morphosys: Consultancy; Abbvie: Consultancy, Research Funding; Genetech: Consultancy; Jannsen: Consultancy; Velosbio: Research Funding; Loxo Oncology: Research Funding; Acerta: Research Funding; Oncternal Pharmaceuticals: Research Funding; SeaGen: Honoraria; GenMab: Consultancy; Epizyme: Consultancy, Research Funding. Ujjani: Abbvie: Consultancy, Honoraria, Research Funding; Atara: Consultancy; Beigene: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Lilly: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Astrazeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Other: Travel expenses , Research Funding; PCYC: Research Funding. Hoffmann: Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria. Cheah: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZenecca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Ascentage Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; AbbVie: Research Funding; Menarini: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; Daizai: Consultancy, Honoraria. Munir: BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lewis: Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Scarfo: Octapharma: Speakers Bureau; Lilly: Consultancy; Janssen: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy. Eyre: Eli Lilly and Company: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Loxo Oncology: Consultancy, Honoraria, Other, Speakers Bureau; KITE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Autolus: Consultancy; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Loxo Lilly: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; PeerView: Speakers Bureau; Medscape: Speakers Bureau; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Alencar: Lilly: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; SeaGen: Membership on an entity's Board of Directors or advisory committees; Dr Reddy: Honoraria; Genentech: Membership on an entity's Board of Directors or advisory committees. Cohen: Genentech: Research Funding; BMS/Celgene: Research Funding; Novartis: Research Funding; BioInvent: Research Funding; Lam Therapeutics: Research Funding; Takeda,: Research Funding; ADCT: Consultancy; AstraZeneca: Consultancy, Research Funding; Abbvie: Consultancy; Janssen: Consultancy; BeiGene: Consultancy; Loxo/Lilly: Consultancy, Research Funding. Zelenetz: Abbvie: Research Funding; SAB: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; MEI Pharma Inc: Consultancy, Honoraria, Research Funding; Janssen Pharmaceuticals: Consultancy, Honoraria; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; None other than mutual funds (401K): Current equity holder in publicly-traded company; BMS: Consultancy, Honoraria. Tsai: Eli Lilly and Company: Current equity holder in publicly-traded company; Loxo@Lilly: Current Employment. Li: Eli Lilly and Company: Current Employment, Current equity holder in publicly-traded company. Bian: Eli Lilly and Company: Current Employment, Current equity holder in publicly-traded company. Abada: Eli Lilly and Company: Current Employment, Current equity holder in publicly-traded company. Zinzani: EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ASTRAZENECA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC THERAPEUTICS: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; INCYTE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BEIGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
OffLabel Disclosure: Pirtobrutinib is approved in the USA to treat R/R mantle cell lymphoma after at least two lines of systemic therapy including prior BTKi treatment.