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5097 Impact of Novel Therapies (NTs) on Real-World (RW) Clinical Outcomes of Patients (pts) with Relapsed/Refractory (RR) Mantle-Cell Lymphoma (MCL) By Race/Ethnicity and TP53 Mutation Status

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphomas, Health outcomes research, Clinical Research, Diseases, Real-world evidence, Lymphoid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Tycel J. Phillips, MD1, Alexey V. Danilov, MD, PhD2, Jia Ruan3, Krish Patel, MD4*, Anita Kumar, MD5, Yucai Wang, MD, PhD6, Gregory A. Maglinte7*, Erlene Seymour7* and Manali Kamdar, MD, MBBS8*

1City of Hope, Duarte, CA
2City of Hope National Medical Center, Duarte, CA
3Weill Cornell Medicine, New York, NY
4Swedish, Seattle, WA
5Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
6Mayo Clinic, Rochester, MN
7BeiGene, San Mateo, CA
8University of Colorado, Boulder, CO

Introduction: Treatments for R/R MCL have evolved with NTs, including BTK inhibitors (BTKis). Little is known about RW treatment patterns and clinical outcomes of pts with R/R MCL for chemoimmunotherapy (CIT) vs NTs among pts of different race/ethnicity. Data on RW testing and clinical outcomes of pts with R/R MCL harboring a TP53 mutation are limited.

Methods: This retrospective cohort study included adult pts with R/R MCL who initiated second-line (2L) or third-line (3L) treatment on 1/1/2018 or later and were followed up until loss to follow-up, death, or data cut-off using US Flatiron Health electronic health record-derived de-identified databases. Median RW time to next treatment (mrwTTNT) and median RW overall survival (mrwOS) were estimated based on Kaplan–Meier analyses and adjusted for age and sex. CIT included any MCL treatment with chemotherapy + anti-CD20 antibody. NTs included BTKis, BCL2 inhibitors, lenalidomide, bortezomib, and CAR-T, or combinations.

Results: This study included 1,377 pts with R/R MCL who received 2L+ therapy. Of these, 1,028 (75%) were non-Latinx (NL)-White, 53 (4%) were NL-Black, 86 (6%) were Latinx, 108 (8%) were NL-Asian or other race, and 102 (7%) were of unknown/undocumented race. The overall 2L+ population had a median age of 71 y (range 63-78), were mostly male (74%), had a diagnosis of MCL not otherwise specified (NOS; 85%), and had stage IV disease (62%). Sixty-three percent had disease progression within 24 mo from first-line (1L) treatment (POD24) before starting 2L therapy. Relative to all pts, NL-Black and NL-Asian/other race pts had more variants of MCL (blastic, leukemic, pleomorphic) and higher Ki67% and lactose dehydrogenase (LDH) levels at 2L/3L index date. In contrast, Latinx pts had more MCL NOS (92%) and lower Ki67% and LDH levels at 2L index date. More NL-Black and unknown race pts had POD24 than did other races (70% and 76%, respectively).

Overall, the most common NTs used were BTKis. 1L treatments were bendamustine-rituximab (BR; 54%), R-CHOP (18%), and cytarabine-containing CIT (9.7%). The most common 2L treatments were BR (32%), acalabrutinib (31%), ibrutinib (21%), zanubrutinib (11%), and R­CHOP (11%). The most common 3L therapies were BR (34%), acalabrutinib (21%), zanubrutinib (12%), ibrutinib (10%), R-CHOP (9.2%), and brexucabtagene autoleucel (7.4%). Transplantation rates before 2L and CAR-T use in 3L was highest among White pts.

When assessing mrwTTNT and mrwOS by therapy in 2L, 766 pts (70%) received NTs and 333 (30%) received CIT. Among all pts, mrwTTNT (mo [95% CI]) was longer with 2L NT (11.9 [10.6, 14.5]) vs CIT (9.9 [8.1, 12.9]). NL-White, NL-Black, and NL-Asian/other race pts had longer mrwTTNT with NT (11.9 [10.5, 14.6], 12.9 [7.6, NR], and 14.6 [8.5, 21.4], respectively) vs CIT (9.9 [7.6, 12.9], 9.7 [3.0, NR], and 6.0 [3.2, 21.2]). Latinx pts had longer mrwTTNT with CIT (14.9 [11.8, NR]) vs NT (9.0 [3.8, 24.2]).

Among all pts, mrwOS (mo [95% CI]) was longer with 2L CIT (43.0 [34.1, 56.5]) vs NT (35.6 [29.9, 41.2]). White and Latinx pts had longer mrwOS with CIT (47.3 [33.9, NR] and NR [33.3, NR], respectively) vs NT (35.0 [28.8, 48.4] and 42.3 [31.0, NR]). Black and Asian/other race pts had longer mrwOS with NT (41.2 [32.8, NR] and 38.8 [23.5, NR], respectively) vs CIT (34.8 [9.7, NR] and 13.5 [8.3, NR]).

Among all 3L pts (n=364 on NTs, n=119 on CIT), mrwTTNT (mo [95% CI]) improved when using NTs (7.9 [6.8, 10.3]) vs CIT (4.4 [3.5, 6.9]). NTs demonstrated better mrwTTNT vs CIT in all race/ethnic groups except Latinx pts. For all race/ethnic groups, mrwOS was improved with NTs (32.5 [24.7, 42.6]) vs CIT (19.5 [13.7, 47.3]).

Overall RW testing for TP53 aberrations was limited, with 72 pts (5%) found to be positive for a TP53 mutation. For pts with TP53 mutations, mrwTTNT and mrwOS were longer for 2L NTs (3.3 [2.2, 6.4] and 18.3 [9.0, NR], respectively; n=42) vs CIT (3.0 [1.9, 7.6] and 15.0 [7.2, NR]; n=16).

Conclusions: High-risk features, treatment patterns, and clinical outcomes for NTs vs CIT in R/R MCL differed by race/ethnicity. Use of 2L+ NTs was associated with a trend towards improved mrwTTNT and mrwOS among NL-Black and NL-Asian/other race pts. NT use in 3L numerically improved mrwTTNT and mrwOS for most pts vs CIT. RW pts with TP53 mutations had a poor prognosis and numerically improved outcomes with the use of 2L NT, although testing remains limited. Future research evaluating reasons for these differences and increased RW TP53 testing is warranted.

Disclosures: Phillips: Genentech: Consultancy; Pharmacyclics/Janssen: Research Funding; ADC Therapeutics: Consultancy; Lymphoma & Myeloma Connect: Honoraria; AbbVie: Research Funding; Celgene: Consultancy; Genmab: Consultancy; Kite/Gilead: Consultancy; TG Therapeutics: Consultancy; Curis: Consultancy; Gilead Sciences: Consultancy; Bayer: Consultancy, Research Funding; Incyte: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Consultancy, Honoraria. Danilov: BeiGene: Consultancy; Merck: Consultancy; Bayer Oncology: Research Funding; GenMab: Consultancy, Research Funding; Genentech: Consultancy; Cyclacel: Research Funding; AstraZeneca: Consultancy, Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; Incyte: Consultancy; Janssen: Consultancy; Lilly Oncology: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Morphosys: Consultancy; Takeda Oncology: Research Funding; TG Therapeutics: Research Funding; Nurix: Consultancy, Research Funding; Prelude: Consultancy; ADCT: Consultancy; Abbvie: Consultancy, Research Funding. Ruan: AstraZeneca: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Janssen: Honoraria; SecuraBio: Honoraria; Kite Pharma: Other: Personal fees outside the submitted work. Patel: Caribou: Consultancy; BMS: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Loxo: Consultancy, Research Funding; Nurix: Consultancy, Research Funding; Xencor: Consultancy, Research Funding; Sana: Consultancy; Pfizer: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Fate Therapeutics: Consultancy, Research Funding; Century: Research Funding; CRISPR: Research Funding; Curis: Research Funding; Pharmacyclics: Research Funding. Kumar: BridgeBio Pharmaceuticals: Current equity holder in publicly-traded company; Adaptive Biotechnologies, Celgene, Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals, Janssen: Honoraria; Loxo Oncology/Lily Pharmaceuticals: Honoraria, Research Funding; Abbvie Pharmaceuticals: Research Funding; Astra Zeneca: Honoraria, Research Funding. Wang: Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding; Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; InnoCare, AbbVie: Consultancy; Kite: Honoraria. Maglinte: Amgen: Current equity holder in publicly-traded company; Gilead: Current equity holder in publicly-traded company; CRISPR Therapeutics: Consultancy, Current equity holder in publicly-traded company; BeiGene: Consultancy, Current Employment, Current equity holder in publicly-traded company. Seymour: Roche: Current holder of stock options in a privately-held company; Flatiron Health (subsidiary of Roche): Ended employment in the past 24 months; BeiGene: Current Employment, Current holder of stock options in a privately-held company, Other: Support for attending meetings and/or travel; Receipt of equipment, materials, drugs, medical writing, gifts or other services, Research Funding. Kamdar: Genentech: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; SeaGen: Speakers Bureau; TG Therapeutics: Research Funding.

*signifies non-member of ASH