Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, indolent lymphoma, real-world evidence, Therapies, Lymphoid Malignancies
METHODS. We performed a retrospective analysis of 54 pts with tFL treated with CAR-T cell therapy from January 2018 to December 2022. Pathological evidence of histologic transformation (HT) was confirmed. The main clinical-biological characteristics of the pts were extracted from the electronic medical records. Cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT guidelines. Progression-free (PFS) and overall survival (OS) were measured from the time of CAR-T cell infusion; PFS events were death, relapse, and disease progression.
RESULTS. Within our cohort of patients with tFL, the median age was 67 years (range 42-81), 65% were male and 77% had stage III-IV disease. Eight of the pts (15%) had an ECOG Performance Status (ECOG-PS) ≥2. Median time to transformation was 27 months from original FL diagnosis (range 0 to 223), including 6 cases with composite lymphoma (FL + aggressive histology) and 4 with synchronous transformation. Twenty percent presented with high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements. Using Hans' algorithm, 85% (44/52) were identified as a germinal center B-cell origin (GCB). In 22 cases, targeted sequencing using the MSK-IMPACT panel was performed at the time of HT or prior to CAR-T. TP53 mutation/deletion was present in 50% of the cases (Figure 1).
Pts received a median of 3 (range 1-9) prior lines of therapy including those for FL, and 9 pts (17%) had undergone prior autologous stem cell transplantation (SCT). Thirty-four pts (63%) were refractory to the last therapy, including 29 pts (53.7%) with primary refractory disease after HT. Forty-one pts (76%) received bridging therapy.
Seventy-two percent of pts received axi-cel, 19% tisa-cel, and 9% liso-cel. CRS of any grade was seen in 43 (80%) pts with grade >3 in 3 (6%). Neurologic toxicity of any grade was observed in 20 (37%) pts with grade >3 in 7 (13%). The median duration of follow-up was 26.2 months. The overall response rate was 87%, including 67% complete response (CR). The median response duration (DOR) was 11 months, with a 2-year DOR of 42% (95% CI: 28-61%). Objective responses were achieved in pts with high-risk features such as HGBCL, TP53 mutation, and chemotherapy-refractory disease.
Twenty-nine pts experienced relapse/progression during follow-up, with a median PFS for the entire cohort of 9.8 months and a 2-year PFS of 40% (95% CI: 28.3-56.3%) (Figure 2). Refractory disease after HT and high LDH serum levels were associated with a significantly lower PFS (median PFS not reached vs. 6.4 months, P=0.031; 24.4 vs. 3.2 months, P=0.003 respectively). Notably, all pts who achieved PR eventually progressed. In 23 pts with relapse, a biopsy was obtained, showing DLBCL or HGBCL morphology in all instances. Interestingly, all relapses occurred during the first 24 months. Twenty-six pts received salvage therapy after CAR-T progression, with a median of 1 line (range 1-7). Out of these, eight (31%) pts achieved a CR and went to allogenic SCT as a consolidative strategy.
Twenty-two pts died during follow-up, 19 due to progression and 3 of non-lymphoma causes, including 2 of COVID-19 infection. The median OS was 31 months, and the 2-year OS rate was 57% (95% CI: 44.3–73.8%) (Figure 2). Median OS was not reached among the 36 pts who achieved a complete response.
CONCLUSIONS. CD19-targeting CAR-T cell therapy is effective for pts with relapsed/refractory tFL, including patients with characteristics of poor prognosis, with efficacy and toxicity profiles comparable to that observed in previous DLBCL studies. Unfortunately, pts who relapse post-CAR-T therapy have limited effective therapeutic options available, and this currently remains an unmet medical need within the field.
Disclosures: Epstein-Peterson: Amgen: Research Funding; WebMD: Honoraria; OncLive: Honoraria; Kymera: Research Funding; Viracta: Research Funding. Falchi: ADC Therapeutics: Other: Advisory Board; Seagen: Other: Advisory Board; AstraZeneca: Other: Advisory board; Abbvie: Consultancy, Honoraria, Other: Advisory Board, travel reimbursement, Research Funding; Genentech: Consultancy, Honoraria, Other: Advisory Board, Research Funding; Roche: Consultancy, Research Funding; Genmab: Consultancy, Honoraria, Other: Travel reimbursement, Research Funding; Ipsen: Other: Advisory board; Evolveimmune: Consultancy; Innate Pharma: Research Funding. Hamlin: ADC Therapeutics: Consultancy. Johnson: Myeloid Therapeutics: Consultancy. Kumar: Genentech: Consultancy, Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Loxo/Lily Oncology: Consultancy, Research Funding; Beigene: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; BridgeBio: Current equity holder in publicly-traded company; Adaptive Biotechnologies: Research Funding; Pharmacyclics: Research Funding; Astra Zeneca: Consultancy, Research Funding; Abbvie Pharmaceuticals: Research Funding. Lue: OncLive: Consultancy; Merck: Consultancy. Scordo: Amgen, Inc.: Research Funding; Omeros Corporation: Consultancy, Research Funding; Medscape, LLC: Honoraria; CancertNetwork (Intellisphere LLC): Honoraria; Angiocrine Bioscience, Inc.: Research Funding. Dogan: Seattle Genetics: Consultancy; Physicians' Education Resource: Consultancy, Honoraria; EUSA Pharma: Consultancy; Loxo: Consultancy; Peer View: Honoraria; Incyte: Consultancy; Takeda: Other: Research Funding; Roche: Other: Research Funding. Zelenetz: Abbvie: Research Funding; MEI Pharma Inc: Consultancy, Honoraria, Research Funding; Janssen Pharmaceuticals: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; SAB: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; None other than mutual funds (401K): Current equity holder in publicly-traded company; BMS: Consultancy, Honoraria; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees. Perales: Astellas: Consultancy, Honoraria; Allogene: Research Funding; Servier: Other; Sellas Life Sciences: Consultancy; Miltenyi Biotec: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Research Funding; Medigene: Consultancy, Other; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Exevir: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; VectivBio AG: Consultancy, Honoraria; Omeros: Consultancy, Current equity holder in publicly-traded company, Honoraria; Caribou: Consultancy, Honoraria; Equillium: Consultancy, Honoraria; DSMB: Other; BMS: Consultancy, Honoraria; Vor Biopharma: Consultancy, Honoraria; Allovir: Consultancy; Adicet: Honoraria; Celgene: Honoraria; Orcabio: Consultancy, Current equity holder in publicly-traded company, Honoraria; Cidara Therapeutics: Consultancy, Other; Syncopation: Honoraria; NexImmune: Consultancy, Current equity holder in publicly-traded company; Merck: Consultancy, Honoraria; Nektar Therapeutics: Consultancy, Honoraria, Research Funding. Palomba: BMS: Honoraria; Cellectar: Honoraria; Ceramedix: Honoraria; Juno: Honoraria, Patents & Royalties; Kite: Honoraria; MustangBio: Honoraria; GarudaTherapeutics: Honoraria; Novartis: Honoraria; Pluto Immunotherapeutics: Honoraria; Rheos: Honoraria; Seres Therapeutics: Honoraria, Patents & Royalties; Smart Immune: Honoraria; Thymofox: Honoraria; Synthekine: Honoraria. Shah: BMS: Research Funding; Beyond Spring: Research Funding; ArcellX: Other: DSMB; Janssen: Research Funding; Amgen: Research Funding. Salles: Owkin: Current holder of stock options in a privately-held company; Molecular Partners: Consultancy; Janssen: Consultancy, Research Funding; ATB Therapeutics: Consultancy; Merck: Consultancy, Honoraria; EPIZYME: Consultancy; Nordic Nanovector: Consultancy; AbbVie: Consultancy, Honoraria; Nurix: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy; BMS/Celgene: Consultancy; Loxo/Lilly: Consultancy; Kite/Gilead: Consultancy; Incyte: Consultancy; Genmab: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; BeiGene: Consultancy; Orna: Consultancy; Ipsen: Consultancy, Research Funding.