Top News in Lymphoma Cell Therapy for World Lymphoma Awareness Day 2025

According to Lymphoma Research Foundation, lymphoma is defined as cancer of the lymphatic system, and includes over 100 subtypes. Although the Foundation notes that every patient's case is different, lymphoma is broadly categorized as either Hodgkin lymphoma or nonHodgkin lymphoma (NHL).

In recent years, cell therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has become a mainstay of the lymphoma treatment landscape, as well as a continued area of interest for novel therapeutic development. In honor of World Lymphoma Awareness Day, observed annually on September 15 by the patient and clinician communities, CGTLive® is taking a look back at some of our news and interviews on the topic of lymphoma from the past few months. Click the "READ MORE" buttons for more details and information about each item.

August 14, 2025 — Results from the phase 2 portion of a phase 1/2 trial (NCT04186520) published in the Journal of Clinical Oncology showed that the prespecified efficacy threshold for 90-day complete response (CR) rate was exceeded in patients with relapsed/refractory (r/r) mantle cell lymphoma (MCL) who were treated with an on-site manufactured, dual-targeted anti-CD20 and -CD19 CAR T-cell therapy (LV20.19). At a fixed dose of 2.5 × 10⁶ cells/kg, treatment in the form of a single infusion of IL-7/IL-15–expanded LV20.19 CAR T-cells yielded a best overall response rate (ORR) of 100%, an 88% complete response rate, and a 12% partial response rate. Furthermore, disease relapse was recorded in only 2 patients at a median follow-up of 15.8 months. At this time point, the median progression-free survival and the median overall survival had not been reached. With regard to safety, there were cases of cytokine release syndrome (CRS) reported in 94% of the patients. All cases were grade 1 or 2 in severity. In 18% of patients immune effector cell–associated neurotoxicity syndrome (ICANS) was reported, with 2 of the cases being deemed reversible grade 3 toxicities. There were 3 nonrelapse mortality events reported, with all having the context of ongoing B-cell aplasia.

August 13, 2025 — Galapagos' GLPG5101, an investigational CD19-directed CAR T-cell therapy product, has received regenerative medicine advanced therapy (RMAT) designation from the FDA for the treatment of r/r MCL.

The RMAT designation was granted based on data from patients with R/R B-cell non-Hodgkin lymphoma treated in the phase 1/2 ATALANTA-1 clinical trial (NCT06561425), which includes a subset of patients with R/R MCL. According to Galapagos, among the findings were “high objective and high complete response rates.” The safety profile was characterized as “manageable”, with rates of high-grade cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome being low. The company also stated that rates of participants dropping out of the trial were also low.

“This designation reflects the promising clinical activity and safety profile observed in our ongoing phase 1/2 study and supports our commitment to delivering an effective and timely treatment option to patients in need,” Omotayo Fasan, MRCP, DTM&H, MBBS, the head of the clinical development program at Galapagos, said in a statement. “With RMAT status allowing for closer collaboration with the FDA, this will enable additional opportunities for accelerated development and assessment timelines.”

August 4, 2025 — Bristol Myers Squibb’s supplemental biologics license application (sBLA) for marketed autologous CD19-directed CAR T-cell therapy lisocabtagene maraleucel (liso-cel, marketed as Breyanzi) for marginal zone lymphoma (MZL) has been accepted by the FDA with priority review. The Prescription Drug User Fee Act goal date for the sBLA has been set for December 5, 2025.

Specifically, the sBLA is under review for adults with R/R MZL who have been treated with 2 or more previous lines of systemic therapy. The sBLA is supported by data from the phase 2 TRANSCEND FL clinical trial (NCT04245839).

“While initial therapy for MZL can be effective, multiple relapses over the course of several years are common, leaving patients in need of a new treatment option that can provide high, lasting response rates,” Rosanna Ricafort, the vice president and head of Late Development Program Leadership, Hematology and Cell Therapy, at BMS, said in a statement. “This FDA acceptance brings us one step closer to potentially standardizing CAR T-cell therapy as a treatment option for MZL, while building on our commitment to bring this personalized therapy to as many eligible patients as possible.”

August 4, 2025 — A patient treated in Allogene Therapeutics’ phase 2 ALPHA3 clinical trial (NCT06500273), which is evaluating investigational CD19-directed allogeneic CAR T-cell therapy cemacabtagene ansegedleucel (cema-cel) as a first-line consolidation treatment for LBCL, has died.

Notably, the patient was treated in an arm of the trial evaluating a lymphodepletion regimen consisting of fludarabine and cyclophosphamide and anti-CD52 monoclonal antibody ALLO-647 (FCA), and the patient’s death was attributed to this lymphodepletion regimen rather than to cema-cel itself. Specifically, the patient’s death was attributed to hepatic failure that was thought to have arisen from “disseminated adenovirus infection in the setting of immune suppression”. The patient’s death occurred 54 days after infusion and was attributed to ALLO-647 specifically.

ALPHA3 also includes a separate arm using only a standard fludarabine and cyclophosphamide (FC) lymphodepletion regimen, and Allogene noted that no adenoviral infections or hepatic failures have been reported in patients treated in the FC arm in ALPHA3, nor in any of the company’s other clinical trials utilizing an FC regimen. As such, Allogene stated that it has selected FC as the lymphodepletion regimen to be used going forward in ALPHA3, a decision it made following discussions with the FDA and with the study’s data and safety monitoring board and steering committee.

June 13, 2025 — A dual-target mCD19/hCD20 CAR-T therapy has demonstrated a 63.6% complete remission (CR) rate in a study that treated 11 patients with r/r B-NHL. The data were presented in a poster at the European Hematology Association (EHA) 2025 Congress, held June 12 to 15, both virtually and in Milan, Italy, by Liu Rui, of the Department of Lymphoma and Myeloma Research Center, at Beijing Gobroad Hospital, in Beijing, China.

The overall response rate for the treated patients was 8 out of 11 (72.7%) at 3 months posttreatment, with 7 patients (63.6%) having achieved at CR at this time point. Furthermore, Rui and colleagues reported that median overall survival and median progression-free survival were not reached at a median follow-up of 20.42 months. It was additionally noted that a median peak expansion value of 6,696 copies was observed, and that 7 days posttreatment constituted the median time to peak expansion.

With regard to safety, CRS occurred in 7 of 11 patients (63.6%). There were no cases of CRS assessed as grade 3 or higher in severity. No cases of ICANS were reported in the study.