Type: Oral
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: 'In with the Old, In with the New': Outcomes of Conventional and Novel Therapeutic Paradigms in Aggressive Lymphoid Malignancies
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Clinical Research, B Cell lymphoma, Patient-reported outcomes, Diseases, Therapy sequence, Real-world evidence, Aggressive lymphoma, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Patients (pts) with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) after CD19 chimeric antigen receptor (CAR)-T cell therapy are challenging to treat. CD20xCD3 T-cell-engaging bispecific antibodies (BsAbs) have emerged as a promising therapeutic option for these pts. In the pivotal trials, glofitamab and epcoritamab demonstrated notable efficacy, with an overall response rate (ORR) of at least 50% and a complete response rate (CR) of at least 34% after CAR-T cell therapy. However, data on the efficacy and safety of BsAbs post-CAR-Ts in the real-world setting are scarce.
Methods
To assess the efficacy and feasibility of BsAbs in the post CAR-T population, we conducted a retrospective, multicenter, multinational analysis, enrolling 85 pts with r/r LBCL treated with BsAbs across 20 centers in Germany, Austria, and Switzerland. Pts were eligible for the study if they had experienced CAR-T cell failure. We defined early ((within first 3 months (mo)), intermediate (4-6 mo) and late (>6 mo) CAR-T cell failure and assessed efficacy (ORR, CR, PR, mPFS, mOS) and feasibility of BsAbs in the real-world setting depending on these time points. Furthermore, information on treatment between CAR-T and following BsAb was collected.
Results
The study cohort included de novo diffuse large B-cell lymphoma (DLBLC) (55/85), transformed indolent lymphoma (18/85), high grade B-cell lymphoma (HGBCL) ((10/85; MYC & BCL2/BCL6 rearrangements (5/10); not otherwise specified (NOS) (4/10); or 11q deletion (1/10)), primary mediastinal B-cell lymphoma (PMBCL) (1/85) and T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) (1/85). Before receiving BsAbs, 43 (51%) pts presented with early (mo 1-3), 24 (28%) with intermediate (mo 4-6), and 18 (21%) pts with late (>6 mo) relapse post-CAR-Ts. Moreover, 51 out of 85 pts (60%) received BsAbs directly after CAR-T failure (immediate BsAb group), while 34 (40%) had a median of one therapy (range 1-4) prior to BsAbs (non-immediate BsAb group). Glofitamab (75/85) was the most commonly administered BsAb followed by epcoritamab (9/85) and mosunetuzumab (1/85).
Overall, 42% of pts responded to BsAbs, with 23% achieving CR and 19% partial response (PR). The ORR varied based on the timing of BsAbs application (47% immediate vs. 35% non-immediate, p=0.282) and CAR-T cell failure (30% vs. 50% vs. 61% in early, intermediate and late relapse post-CAR-Ts, p=0.019). The highest CR rate was observed in pts with late CAR-T failure (44%), followed by intermediate (25%) and early (14%) groups (p=0.037). The median progression-free survival (mPFS) was 3.27 mo, while the median overall survival (mOS) was 6.83 mo. Estimated mPFS was significantly better in the immediate than in the non-immediate BsAb group (4.37 mo vs. 2.48 mo, p=0.026) while mOS did not differ significantly (7.73 mo vs 5.10 mo, p=0.100). Additionally, mPFS and mOS differed significantly in early (2.13 and 4.10 mo), intermediate (3.73 and 7.73 mo) and late (10.46 mo and not reached) CAR-T failure groups, accordingly (p≤0.004).
In the multivariate analysis, sensitivity to the last treatment prior BsAbs (PFS - [HR=2.31, p=0.004]; OS - [HR=2.81, p=0.006]), the timepoint of CAR-T failure (PFS - [HR=1.48, p=0.05]; OS - [HR=1.94, p=0.011]), additional therapies between CAR-T and BsAb (PFS - [HR=1.86, p=0.039]) and LDH levels before application of BsAb considered as continuous variable (p=0.049 for PFS) were the strongest predictors of survival after initiation of BsAbs.
The frequency of cytokine release syndrome (CRS) was 31%, with grades 3-4 documented in 3%. Severe immune effector cell-associated neurotoxicity syndrome (ICANS) occurred only in one patient (1%) (grade 3). Infections were documented in 36% of pts, with grades 3 in 11% and three pts with grade 5 (all associated with COVID-19).
Conclusions
In summary, BsAbs show efficacy and manageable safety profiles in r/r LBCL pts following CAR-T failure in real-world settings. However, efficacy of BsAb is significantly impaired in early CAR-T refractory pts underscoring the necessity of novel therapeutic approaches in these pts.
Disclosures: Shumilov: Gilead: Consultancy, Honoraria, Other: Travel and congress support; BMS: Consultancy, Honoraria; Incyte: Honoraria; Oncopeptides: Consultancy, Honoraria, Other: Travel and congress support; Stemline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and congress support; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria, Other: Congress support. Vucinic: Gilead/Kite, Janssen, BMS Celgene, Novartis: Consultancy, Honoraria; Amgen: Honoraria, Other: Travel grant. Holtick: Roche: Honoraria. Scholz: Beigene, Abbvie, Janssen, Novartis: Other: travel support . Melchardt: Abbvie, Roche: Honoraria. Schultze-Florey: Janssen: Consultancy, Honoraria, Other: Travel support, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Other: Travel support; Pierre Fabre: Consultancy, Honoraria, Other: Travel support; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Abbvie: Other: Travel support. Lesan: Pierre Fabre: Other: Travel and Congress Grant. Schnetzke: Abbvie, Novartis, Kite Gilead, BMS, Janssen, Sobi, Takeda, Beigene: Consultancy, Honoraria, Other: travel support . Kerkhoff: Abbvie: Honoraria, Other: Travel- & congress-support; MSD: Honoraria; Takeda: Honoraria; AstraZeneca: Honoraria; BMS: Honoraria, Other: Travel- & congress-support; Amgen: Honoraria; Sobi: Other: Travel- & congress-support; EUSA: Other: Travel- & congress-support; BeiGene: Other: Travel- & congress-support; Roche: Honoraria. Aydilek: Kite Gilead: Honoraria. Gebauer: AstraZeneca: Honoraria; Takeda: Honoraria; Menarini Stemline: Honoraria; Beigene: Honoraria, Other: travel support ; Janssen: Honoraria, Other: travel support. Glass: Riemser, Roche: Other: grants ; Roche, Kite Gilead, BMS: Other: travel support ; Kite Gilead, Novartis, BMS, Roche, Miltenyi, Incyte: Honoraria. Heidel: Novartis, Celgene/BMS, CTI: Research Funding; BMS/Celgene, AOP, Novartis, CTI, Janssen, Abbvie, GSK, Merck, CTI, Kartos, Telios: Consultancy. Viardot: AbbVie, Amgen, Kite, Roche, Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; AbbVie, BMS, Kite, Novartis, Roche, Sobi: Honoraria. Hänel: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Falk Foundation: Honoraria; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: 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; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; BristolMyersSquibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer Vital: 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; BristolMyersSquibb/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Honoraria; Novartis: Honoraria. Dietrich: University Hospital Dusseldorf Germany: Current Employment; F. Hoffmann-La Roche Ltd, Kite: Research Funding; F. Hoffmann-La Roche Ltd, Kite, BMS, AbbVie: Honoraria. Ayuk: Abbvie: Honoraria; Novartis: Consultancy, Honoraria; BMS: Honoraria; Medac: Consultancy, Honoraria; Miltenyi Biomedicine: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding. von Tresckow: AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis: Other: Travel and congress support ; Esteve (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), and Takeda (Inst): Research Funding; AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche and Takeda: Honoraria; Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Regeneron, Roche, Sobi and Takeda: Consultancy. Chapuy: Sobi, Roche: Other: travel support ; AbbVie, Ars tempi, Astra Zeneca, BMS, Incyte, Janssen, Gilead, KML, Roche, Sobi, Ono: Honoraria; AbbVie, Bristol Myers Squibb, Incyte, Janssen, Roche, and Sobi: Consultancy. Lenz: Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Consultancy; Acerta: Research Funding; Sobi: Honoraria, Speakers Bureau; Pierre Fabre: Honoraria; PentixaPharm: Honoraria; NanoString: Honoraria; MSD: Honoraria; Miltenyi Biotech: Honoraria; Lilly: Honoraria; Karyopharm: Honoraria; Incyte: Honoraria; Immagene: Honoraria; Hexal/Sandoz: Honoraria; Genmab: Honoraria; Genase: Honoraria; Constellation: Honoraria; BMS: Honoraria; BeiGene: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; ADC Therapeutics: Honoraria; Verastem: Research Funding; AQUINOX: Research Funding; ELVESCA: Current equity holder in private company; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Membership on an entity's Board of Directors or advisory committees; AbbVie, BeiGene, Sobi, Roche, Gilead, BMS: Other: Travel; Bayer: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; MorphoSys: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Roche: Honoraria, Research Funding; AGIOS: Research Funding; AstraZeneca: Honoraria, Research Funding.
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