Epkinly (epcoritamab-bysp)

Fixed-duration epcoritamab monotherapy showed promising complete response rates and a manageable safety profile in older adults with newly diagnosed DLBCL and comorbidities, with slight differences between stages 1 and 2. Continued investigation of epcoritamab as a first-line chemotherapy-free treatment option is warranted.

CAR-T products achieved overall response rates (ORR) of 52-83% and complete response (CR) rates of 40-58%; randomized second-line trials favored axicabtagene ciloleucel and lisocabtagene maraleucel over standard care...BsAbs were active in heavily pretreated disease (epcoritamab ORR 50%/CR 44%; glofitamab ORR 55%/CR 35%), with predominantly low-grade cytokine release syndrome. Selinexor showed more modest efficacy (ORR 39%/CR 16%) but durable benefit in complete responders.ConclusionsCurrent evidence supports a stepwise treatment framework: DLBCL-like induction at transformation, autologous stem-cell transplant in fit, chemosensitive responders, CAR-T as the preferred option at first relapse, BsAbs after CAR-T or when cellular therapy is not feasible, and selinexor in later-lines of therapy. Additional prospective t-FL-inclusive trials are needed to refine treatment selection and biomarker-guided sequencing.

P1, N=12, Recruiting, University of Utah | Not yet recruiting --> Recruiting

P1/2, N=38, Recruiting, Yazeed Sawalha | Trial completion date: Dec 2028 --> Oct 2027 | Trial primary completion date: Dec 2026 --> Aug 2027

P2/3, N=116, Active, not recruiting, AbbVie Deutschland GmbH & Co. KG | Recruiting --> Active, not recruiting

P2, N=20, Not yet recruiting, Mwanasha Merrill, MD

Among the agents studied, epcoritamab demonstrated the highest ORR...Cytokine release syndrome was the most common toxicity, predominantly grade 1-2, while neurotoxicity and hematologic adverse events were manageable. In conclusion, CD3×CD20 BsAbs exhibit meaningful efficacy and acceptable safety profiles in R/R LBCL patients following CAR-T failure, particularly in those with longer relapse intervals.

P2, N=29, Active, not recruiting, City of Hope Medical Center | Suspended --> Active, not recruiting

P1/2, N=30, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jun 2026 --> Feb 2026

P2, N=43, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Dec 2028 --> Oct 2029 | Initiation date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2028 --> Oct 2029

P1, N=12, Not yet recruiting, University of Utah

P1/2, N=28, Not yet recruiting, Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting | N=14 --> 28