The 2025 American Society of Hematology’s Annual Meeting is currently underway in Orlando, Florida between December 6 to 9. At this conference, researchers testing new and existing treatments for blood cancers have gathered to present their latest results.
People whose lymphoma comes back or does not respond to treatment (relapsed/refractory) often need additional options. This article explains four early studies of newer CAR T-cell therapies and what their results could mean for people with B-cell lymphoma.
KITE-363 and KITE-753 target two markers at once
KITE-363 and KITE-753 are new types of CAR T-cell therapies. CAR-T is a treatment where a person’s own T cells are changed in a lab so they can better find and remove lymphoma cells. These two therapies are designed to recognize both CD19 and CD20, which are markers found on many B-cell lymphoma cells. Targeting two markers may help lower the chance that the lymphoma comes back if one marker disappears.
In this early study, people with relapsed/refractory B-cell lymphoma received KITE-363 or KITE-753 at different doses. Many patients had advanced-stage lymphoma, and some had already tried a prior CAR T-cell therapy.
At the highest doses of these treatments, for KITE-753, 79% of patients experienced complete remission. For those who received KITE-363, 78% of patients experienced complete remission. More than half of these patients continued to remain in remission at the median follow-up of 17.5 months. Although most patients experienced low blood counts, cases of cytokine release syndrome (CRS) and temporary brain-related side effects (ICANS) were uncommon and mostly mild. This suggests these dual-target CAR-T options may be promising for people whose lymphoma is difficult to treat.
Read this abstract: A Phase 1 study of KITE-753 or KITE-363 in patients with relapsed/refractory B-cell lymphoma: Initial safety and preliminary efficacy of KITE-753 and updated results of KITE-363. Data includes updated numbers presented during the ASH conference on December 6, 2025.
LUCAR-G39D: an off-the-shelf dual-target CAR-T
LUCAR-G39D is an allogeneic CAR T-cell therapy. Allogeneic means the T cells come from a donor without cancer instead of the lymphoma patient. This “off-the-shelf” approach may help people receive treatment faster, which can be important when lymphoma is growing quickly. LUCAR-G39D also targets both CD19 and CD20 to reduce the chance that lymphoma cells escape by losing one marker.
In this small phase 1 study, 10 adults with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma and follicular lymphoma, received an infusion at different dose levels. Of all patients, 75% experienced a reduction in cancer cells, with 37.5% experiencing complete remission. At 14.6 months, 83.3% of patients remained in remission. Most side effects were related to low blood counts or mild to moderate infections. CRS occurred in 4 people and was mostly mild, and there were no cases of neurotoxicity or graft-versus-host disease, which can sometimes occur with donor cells. For patients who cannot access or wait for standard CAR T-cell therapy, an off-the-shelf option like LUCAR-G39D may provide another path in the future.
Read this abstract: A phase 1 study of lucar-G39D: A novel anti-CD20/CD19 dual-CAR allogeneic gamma delta T cells in adults with relapsed / refractory B-cell non-Hodgkin lymphoma (NHL). Data includes updated numbers presented during the ASH conference on December 6, 2025.
Azer-cel plus IL-2 after prior CAR-T relapse
Azer-cel is an allogeneic CD19-directed CAR T-cell therapy. It is made from healthy donor T cells. This study looked at azer-cel in people with large B-cell lymphoma (LBCL) who had previously received and then relapsed after an autologous CAR T-cell therapy. Autologous means the T cells were their own. These people often have very few effective options. Researchers added an under-the-skin shot of low-dose interleukin-2 (IL-2), a natural protein that can help T cells grow, for 14 days to see if it would help azer-cel work better.
In people treated with azer-cel plus low-dose IL-2, 81% of patients experienced a reduction in cancer cells, with 43.8% experiencing complete remission. Side effects such as CRS and ICANS were mostly mild or moderate. For individuals whose lymphoma returned after their first CAR T-cell therapy, this combination suggests that another CAR-T approach, supported by IL-2, may still offer meaningful benefit.
Read this abstract: Azer-cel, an allogeneic (allo) CD19 CAR T, in combination with low-dose interleukin-2 (IL-2) demonstrates clinical activity in patients with large B-cell lymphoma (LBCL) who relapsed after autologous (auto) CAR T. Data includes updated numbers presented during the ASH conference on December 6, 2025.
BAFFR-CAR T cells for people after CD19-targeted therapy
PMB-CT01 is a BAFFR-CAR T-cell therapy that targets BAFF-R, a receptor that helps B cells survive. Unlike CD19, BAFF-R is often still present even when CD19 is lost, including in people whose lymphoma has stopped responding to CD19-targeted therapies. This makes BAFF-R an appealing target for those who have already tried CD19-directed CAR T-cell therapy or have CD19-negative lymphoma.
In this early phase 1 study, seven people with different B-cell lymphomas, including mantle cell lymphoma and follicular lymphoma, received PMB-CT01 at one of two dose levels. Three months after the CAR-T infusion, 87.5% of patients experienced complete remission, and no patients have relapsed. All CRS events were mild, and only two people had mild ICANS that went away without steroids.
These results suggest BAFFR-CAR T cells may become an important option for individuals whose lymphoma no longer responds to CD19-targeted therapies.
Read this abstract: BAFFR-CAR T cells (PMB-CT01) demonstrate durable responses and manageable toxicities in relapsed/refractory B-cell lymphomas with prior CD19-directed therapy failure or CD19-negative disease. Data includes updated numbers presented during the ASH conference on December 6, 2025.
Key takeaways
These four early studies show several new CAR T-cell therapies that may help people with relapsed or refractory B-cell lymphoma, including those who have already tried a prior CAR-T. Dual-target therapies, off-the-shelf donor CAR-T, and new targets like BAFF-R may offer more chances for long-lasting responses with manageable side effects. Larger and longer studies are still needed, but these results give hope that more personalized and flexible CAR-T options are on the way.
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Sources:
- A Phase 1 study of KITE-753 or KITE-363 in patients with relapsed/refractory B-cell lymphoma: Initial safety and preliminary efficacy of KITE-753 and updated results of KITE-363
- A phase 1 study of lucar-G39D: A novel anti-CD20/CD19 dual-CAR allogeneic gamma delta T cells in adults with relapsed / refractory B-cell non-Hodgkin lymphoma (NHL)
- Azer-cel, an allogeneic (allo) CD19 CAR T, in combination with low-dose interleukin-2 (IL-2) demonstrates clinical activity in patients with large B-cell lymphoma (LBCL) who relapsed after autologous (auto) CAR T
- BAFFR-CAR T cells (PMB-CT01) demonstrate durable responses and manageable toxicities in relapsed/refractory B-cell lymphomas with prior CD19-directed therapy failure or CD19-negative disease
