Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster I
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, CAR-Ts, B-Cell Lymphoma, Lymphoid Malignancies
Methods: We retrospectively reviewed the records of 75 consecutive patients with aggressive B-cell lymphomas treated with commercial CAR-T therapy at the University of Pennsylvania between April 2018 and October 2019. We included all patients with either diffuse large B cell lymphoma or HGBCL who had both: a) fluorescence in situ hybridization testing for MYC, BCL2 and BCL6 chromosomal rearrangements, and b) immunohistochemical staining (IHC) for MYC and BCL2. Patients who had both MYC and BCL2 and/or BCL6 chromosomal rearrangements were classified as DHL; patients with IHC expression of both MYC in > 40% and BCL2 in > 50% of tumor cells without meeting criteria for DHL were classified as DEL. Patient characteristics were collected. Fisher’s exact test was used to compare overall response rate (ORR) and log-rank test was used for comparison of progression-free survival (PFS).
Results: Seventy-five eligible cases of aggressive B-cell lymphoma were identified; 9 were excluded due to non-DLBCL or HGBCL subtype and 16 were excluded due to insufficient characterization of tissue to assess DHL and DEL status. Fifty patients were eligible for analysis; 18 patients (36%) met criteria for DEL, 10 patients (20%) met criteria for DHL, and the remaining 44% of patients had neither DEL nor DHL (non-DEL/DHL). Tisagenlecleucel was administered to 39 patients, whereas axicabtagene ciloleucel was administered to 11 patients. Median age at leukapheresis was 65 years (range: 35-81). LDH, administration of bridging therapy, and ECOG performance status (PS) did not significantly differ between the three groups. Median follow-up for the entire cohort was 15.9 months. For all patients, best ORR was 54% (27/50 patients), median PFS was 3.7 months (95%CI: 2.8-NE), and median OS was not reached. Best ORR was 56% (10/18) for DEL patients, 50% (5/10) for DHL patients, and 55% (12/22) for patients with non-DEL/DHL. ORR did not differ between these groups (p=1.0). There was no difference in PFS (see Figure, p=0.90), OS (p=0.61), or RD (p=0.38) between the three groups. At 16 months, 69% of responding DEL continue in CR (95%CI: 30-89%), 72% of non-DEL/DHL (95%CI: 35-90%) continue in CR, and 100% of DHL (95%CI: NE) continue in CR.
Conclusions: The proportion of patients with DEL in our study was similar to that reported for patients with diffuse large B-cell lymphoma in the literature. There were no significant differences between DEL, DHL, and non-DEL/DHL groups with regard to the proportion of patients with elevated LDH, bridging therapy, or ECOG PS. Although DHL and DEL have a negative prognostic impact on response to salvage therapies and hematopoietic stem cell transplant, neither DHL nor DEL status was associated with inferior response to anti-CD19 commercial CAR-T products. We demonstrate that patients with DEL can achieve prolonged responses after CAR-T. Moreover, neither DEL nor DHL status appeared to impact PFS, OS, or RD outcomes after commercial CAR-T.
Disclosures: Chong: BMS: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Landsburg: Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Triphase: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Gerson: Loxo: Research Funding; Genentech: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy. Svoboda: Atara: Consultancy; Genmab: Consultancy; TG: Research Funding; Adaptive: Consultancy; Astra-Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Imbrium: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding. Dwivedy Nasta: Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Debiopharm: Research Funding; Forty Seven: Research Funding; Incyte: Research Funding; Atara: Research Funding; Rafael Pharmaceuticals: Research Funding. Barta: Pfizer: Honoraria; Monsanto: Consultancy; Atara: Honoraria; Seattle Genetics: Honoraria, Research Funding; Janssen: Honoraria; Acrotech: Honoraria. Garfall: Novartis: Research Funding; Tmunity: Consultancy, Other: Personal fees, Research Funding; Amgen: Research Funding; Kite Pharma: Other: Personal fees; Janssen: Consultancy, Research Funding; GSK: Consultancy; Surface Oncology: Consultancy. Ruella: UPenn/Novartis: Patents & Royalties; Abclon, BMS, NanoString: Consultancy; Abclon: Consultancy, Research Funding. Frey: Syntax: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria. Porter: American Board of Internal Medicine: Other: Member, exam writing committee (end date Oct 2019); Novartis: Honoraria, Other: Advisory board, Patents & Royalties: CAR T cells for CD19+ malignancies, Research Funding; Glenmark: Other: Advisory board; Genentech/Roche: Current equity holder in publicly-traded company, Other: Spouse employment (ended Sept 2020); her salary includes stock/options; Janssen: Other: Advisory board; Adicet bio: Other: Advisory board; Kite/Gilead: Other: Advisory board; Incyte: Other: Advisory board; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Tmunity: Patents & Royalties. Schuster: AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria; Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding.
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