Outcomes of diffuse large/high grade B cell lymphoma patients following receipt of autologous stem transplantation or chimeric antigen receptor‐modified T cells

Abstract

Introduction: High dose chemotherapy/autologous stem cell transplantation (ASCT) and CD19-directed chimeric antigen receptor-modified T cells (CART19) are potentially-curative treatment options for patients (pt) diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) and high grade B cell lymphoma (HGBL). Analysis of a large series of pt receiving ASCT and/or CART19 has not been performed and may reveal differences in treatment failure (TF) which could inform efforts to optimize pt selection for these therapies. Methods: Included pt were age ≤75 years who received ASCT and/or CART19 for R/R DLBCL/HGBL at the University of Pennsylvania between 3/1/13 and 3/1/21. All ASCT pt demonstrated either partial or complete metabolic response to salvage immunochemotherapy (IC). Freedom from TF (FFTF) was defined as the interval between receipt of cell infusion and proven/suspected relapse of lymphoma (DLBCL/HGBL for ASCT pt or any lymphoma for CART19 pt) or last follow-up (f/u) in remission. Data were censored on 3/1/23. Results: Characteristics at the time of relapse preceding ASCT or CART19 are listed in the Table. Minimum prior LOT was 1 for ASCT and 2 for CART19 pt. With a median length of f/u of 62.7 months (mo) for ASCT pt and 37.6 mo for CART19 pt, the estimated (est) rate of FFTF at 36 mo were 59% and 24%, respectively. Cox regression analysis of characteristics predictive of TF at 36 mo revealed history of tIL (hazard ratio [HR] 0.23, P = 0.016) for ASCT pt, and history of tIL (HR 0.48, P = 0.004) as well as IPI score ≥3 (HR 2.7, P < 0.001) for CART19 pt. As depicted in the Figure, ASCT pt experienced significantly higher est rates of FFTF at 36 mo if achieving actual FFTF at 3 mo (64% vs. 38%, P = 0.002), 6 mo (76% vs. 52%, P = 0.02), 12 mo (84% vs. 62%, P = 0.03) and 24 mo (95% vs. 78%, P = 0.03) post-infusion as compared to CART19 pt. For characteristics which predict for TF at 36 mo (no history of tIL and IPI score ≥3), the incidence was either similar or significantly lower for CART19 versus ASCT pt who achieved actual FFTF at 3, 6, 12 and 24 mo. Keyword: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. D. J. Landsburg Consultant or advisory role: Morphosys, Epizyme, Calithera, ADC Therapeutics, Karyopharm Research funding: Curis, Calithera, Epizyme Educational grants: Novartis S. D. Nasta Research funding: Pharmacyclics, Roche, Rafael, FortySeven J. Svoboda Consultant or advisory role: SEAGEN, Pharmacyclics, Incyte, Genmab, BMS, Atara, Astra Zeneca, Adaptive, ADCT Research funding: TG, SEAGEN, Pharmacyclics, Merck, Incyte, BMS, Astra Zeneca J. N. Gerson Consultant or advisory role: Genentech, Abbvie Research funding: Loxo S. J. Schuster Consultant or advisory role: Novartis, Regeneron, Nordic, Morphosys, MustangBio, Incyte, Genentech/Roche, Janssen, Legend Biotech, Loxo, Acerta, BiGene, Celgene, Nanovecter Research funding: Novartis, Pharmacyclics, Merck, DTRM, Juno Therapeutics, Abbvie, Adaptive Biotechnologies, Incyte, Genentech/Roche, Celgene, TG Therapeutics S. K. Barta Consultant or advisory role: Daiichi Sankyo, Kyowa Kirin, Janssen, Affimed Honoraria: Acrotech, Seagen, Kyowa Kirin E. A. Chong Honoraria: Juno/BMS, Novartis, Beigene, KITE, Tessa A. L. Garfall Consultant or advisory role: Jannsen, GlaxoSmithKline, Bristol-Myers Squibb Research funding: Novartis, Tmunity Therapeutics, Janssen, Crispr Therapeutics E. A. Stadtmauer Research funding: BMS, Celgene, Abbvie, Sorrento N. V. Frey Consultant or advisory role: Sana Biotechnology, Kite Pharma, Syndax Pharmaceuticals Research funding: Research Funding D. L. Porter Consultant or advisory role: Novartis, Kite/Gilead, Incyte, Janssen, Jazz, DeCart, BMS, Bluebird Bio, Angiocrine, Mirror Biologics, Capstan Therapeutics, Instill Bio Research funding: Novartis