Outcome of patients with large B-cell lymphoma treated with tafasitamab plus lenalidomide either before or after CAR T-cell therapy

• Published in: Blood advances 2024-10, Vol.8 (20), p.5371-5381
• Main Authors: Camus, Vincent, Houot, Roch, Brisou, Gabriel, Tessoulin, Benoit, Bailly, Sébastien, Sesques, Pierre, Decroocq, Justine, Krzisch, Daphné, Oberic, Lucie, Lemonnier, François, Bouabdallah, Krimo, Campidelli, Arnaud, Tounes, Ledraa, Abraham, Julie, Herbaux, Charles, Morschhauser, Franck, Damaj, Gandhi Laurent, Guidez, Stéphanie, Carras, Sylvain, Fornecker, Luc-Matthieu, Choquet, Sylvain, Hermine, Olivier, Paillassa, Jérome, Chauchet, Adrien, Casasnovas, Olivier, Drieu La Rochelle, Laurianne, Castilla-Llorente, Cristina, Joris, Magalie, Dupont, Vivien, Marquet, Alexandra, Le Gouill, Steven, Jardin, Fabrice
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Female; Humans; Immunotherapy, Adoptive - methods; Lenalidomide - therapeutic use; Lymphoid Neoplasia; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Receptors, Chimeric Antigen; Treatment Outcome
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2024013726

•TAFA combined with LEN showed limited efficacy after CAR T-cell failure in a high-risk population.•Outcomes were comparable between the TAFA-LEN combination and other treatments for the first progression after CAR T-cell therapy. [Display omitted] Tafasitamab plus lenalidomide (TAFA-LEN) treatment relevance pre- or post-anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is debated. We analyzed patients with large B-cell lymphoma in the DESCAR-T registry treated with axi[1]cel or tisa-cel in ≥3rd line and TAFA-LEN before (n = 15, “TL-pre-CAR-T” set) or directly after (n = 52, “TL-post-CAR-T” set) CAR T-cell therapy. We compared TAFA-LEN v. other treatments using inverse probability weighting in the TL-post-CAR[1]T set. In the TL-post-CAR-T set, the median progression-free survival (mPFS), overall survival (mOS), and duration of response (mDOR) since the first treatment for progression (mPFS2/mOS2/mDOR2) were 3, 4.7, and 8.1 months, respectively. The best overall response rate (bORR) and best complete response rate (bCRR) after TAFA-LEN were 13.5% and 7.7%, respectively. Outcomes were better for patients who relapsed >6 months after CAR T-cell therapy (mPFS2: 5.6 vs 2 months, P = .0138; mOS2: not reached vs 3.8 months, P = .0034). The bORR and bCRR between TAFA-LEN and other treatments were 20.6% vs 24.9% and 11.6% vs 15.6%, respectively. Outcomes were similar between TAFA-LEN and other treatments (mPFS2: 2.9 vs 2.4 months, P = .91; mOS2: 3.3 vs 5.5 months, P = .06). In an exploratory analysis of the TL-pre-CAR-T set, the median TAFA-LEN treatment duration before CAR-T was 3.7 months with no patient becoming CD19 negative. The bORR, bCRR, 6- month PFS, and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1%, and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatment improved outcomes for patients relapsing after CAR T-cell therapy.