626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas) - Results from Prospective Clinical Trials:

Rajat Bannerji, John N. Allan, Jon E. Arnason, et al. 

Authors Conclusion from the Abstract: Odronextamab has demonstrated encouraging single-agent antitumor activity in highly refractory pts with B-NHLs. Durable CRs have been observed in both indolent and aggressive B-NHL pts, including in pts refractory to CAR T therapy. Most CRs are ongoing at the time of data cutoff, and updated data will be presented. Odronextamab has an acceptable safety and tolerability profile. Dexamethasone premedication and step-up dosing mitigates the risk for CRS and allows odronextamab administration up to 320 mg weekly without DLTs. A global P2 trial investigating odronextamab in R/R B-NHL is ongoing.

Adam J Olszewski, Abraham Avigdor, Sunil Babu, et al.

Authors Conclusion from the Abstract: Early clinical data indicate that single-agent Mosun confers notable efficacy and remarkable tolerability for previously untreated elderly/unfit DLBCL pts. Mosun is a promising chemotherapy-free regimen for patients who otherwise have limited options.

Martin Hutchings, Rogier Mous, Michael Roost Clausen, et al.

Authors Conclusion from the Abstract: Epcoritamab, a novel SC bsAb, demonstrates a consistent and favorable safety profile, with no grade ≥3 CRS events and limited neurotoxicity, in support of outpatient administration. Emerging data with longer follow-up are highly encouraging, with substantial single-agent efficacy, including CR in heavily pretreated pts with FL, MCL, and DLBCL.

Martin Hutchings, Carmelo Carlo-Stella, Emmanuel Bachy, et al.

Authors Conclusion from the Abstract: Step-up dosing of glofitamab allowed escalation up to 30mg to maximize efficacy, while minimizing the risk of increased CRS. High ORR and CMR rates were observed in pts with NHL who had failed several lines of treatment. Toxicity was manageable with the main safety signal being low-grade CRS observed in early cycles. Updated results will be presented at the congress which will include data from at least 50 pts receiving glofitamab step-up dosing with Gpt.

Peter Borchmann, Anja Jühling, Philipp Gödel, et al.

Authors Conclusion from the Abstract: In this first-in-human dose-finding study of MB-CART2019.1, no DLT, and no severe (grade ≥3) CRS or neurotoxicity were observed. Feasibility and safety were very good in this cohort of elderly r/r B-NHL patients. The sustained expansion of tandem CAR T-cells was accompanied by efficacy: all patients (6/6) treated on DL2 responded and all 5 patients with CR (5/5) are in ongoing remission by the time of this report. Based on the promising risk-to-benefit ratio observed in our study, evaluation of MB-CART2019.1 at a dose of 2.5x106/kg body weight in clinical phase II and phase III trials for patients with relapsed aggressive B-NHL is underway.

Sattva S. Neelapu, Michael Dickinson, Matthew L. Ulrickson, et al.

Authors Conclusion from the Abstract: ZUMA-12 is the first study evaluating CAR T cell therapy as first-line therapy in high-risk LBCL, which notably was defined by both histology and/or IPI and dynamic risk assessment with PET scan. Axi-cel demonstrated significant clinical benefit, with high ORR and CR rates and a manageable safety profile in pts for whom there is an unmet medical need. The study also provides new insights into the pharmacology of CAR T cell therapy for pts exposed to fewer prior therapies.