ASH 2025 Updates Signal Expanding Applications for Immunotherapy and T-Cell Therapies Across Leukemia and Lymphoma

The 2025 ASH Annual Meeting concluded on December 10th, following several days of data-driven discussion highlighting evolving applications of immunotherapies and next-generation targeted agents across hematologic malignancies. Data presented at the meeting underscored continued movement toward fixed-duration regimens, CAR T-cell therapy as consolidation, earlier-line integration of bispecific T-cell–engaging therapies, and increasing personalization of treatment based on disease biology and patient fitness.

During the meeting, OncLive® spoke with the following experts across lymphoma and leukemia to identify the studies and topics they viewed as most influential for short-term clinical practice and future research directions:

• Lori Leslie, MD, director of the Indolent lymphoma and chronic lymphocytic leukemia research programs at John Theurer Cancer Center and assistant professor at Hackensack Meridian School of Medicine.
• Paolo Strati, MD, an associate professor in the Department of Translational Molecular Pathology and Department of Lymphoma/Myeloma, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, Houston, Texas; as well as an international faculty member, in the Department of PhD program in Clinical and Experimental Oncology and Immunology, at University of Padova, Padua.
• Anand A. Patel, MD, an assistant professor of medicine and medical director of Inpatient Leukemia Service at the University of Chicago Medicine.
• Tatyana A Feldman, MD, a medical oncologist at Hackensack Meridian Health
• Fadi Haddad, MD, an assistant professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center.
• David J. Andorsky, MD, a medical oncologist/hematologist at Rocky Mountain Cancer Centers and an associate chair for US Oncology Hematology Research.
• Jeff P. Sharman, MD, a medical oncologist/hematologist and director of research at the Willamette Valley Cancer Institute, as well as the medical director of hematology research for The US Oncology Network.

For those who missed the meeting in Orlando, Florida, check out their unique perspectives and insights below. To read additional insights from experts on the top studies presented in AML, marginal zone lymphoma, and myeloma, click here!

What data from ASH 2025 have helped expand treatment options in relapsed/refractory follicular lymphoma?

Leslie: I was excited about the presentation of [primary data] from the [phase 3] EPCORE FL-1 [trial (NCT05409066)], which is looking at [fixed-duration] rituximab [Rituxan] and lenalidomide [Revlimid; R2] plus epcoritamab-bysp [Epkinly] in relapsed/refractory follicular lymphoma. These data led to the recent FDA approval of this combination in November 2025 for patients in the second-line setting.1 That’s a really promising update, and very big news from this year’s meeting.

There are a lot of updates in the field of cellular therapy for lymphomas. That’s the most appealing progress that we’ve made in the lymphoma community as a whole, with many updates moving cell therapies as early as the front line in certain studies.

Strati: The biggest news from the meeting in follicular lymphoma is results from the EPCORE FL-1 study comparing the combination of epcoritamab and R2 in patients with relapsed/refractory follicular lymphoma. Thanks to this study, the FDA approved the combination in the second line and beyond for patients with follicular lymphoma. This is huge for multiple reasons. If you look into the data, the complete response [CR] rates were close to 90% compared with historical [CR rates between] 20% to 30%, and there was an approximately 80% increase in progression-free survival rates.

We also have to remind ourselves that another randomized phase 3 trial—one that was double-blinded where placebo was utilized—the phase 3 inMIND trial [NCT04680052] also recently brought about the FDA approval of tafasitamab-cxix [Monjuvi] plus R2[for relapsed/refractory follicular lymphoma in June 2025].2 Tafasitamab is a monoclonal antibody targeting CD19.

There are many effective options in this setting now. Quality-of-life studies demonstrate that both tafasitamab/R2 and epcoritamab/R2 can be very well tolerated. Real-world experience will tell us in the next few months how this will help our patient population.

What were the top takeaways from the diffuse B-cell lymphoma (DLBCL) and B-cell acute lymphocytic leukemia (B-ALL) sessions at ASH 2025?

Feldman: What was really pleasing to see was the moving of bispecific T-cell engagers into the frontline settings in elderly patients with DLBCL or follicular lymphoma, thus creating regimens for patients who cannot tolerate chemotherapy. There is one trial that I would like to follow, because everything is about immunotherapy: [the phase 1 CA1231000 study (NCT06090539) evaluating BMS-986458]. This BCL-6 degrader, as a small molecule, showed very impressive results in patients who actually [progressed on] immunotherapy, CAR T-cell therapy, transplant, and bispecific T-cell engagers, and it showed very remarkable overall responses and CRs in patients with relapsed/refractory non-Hodgkin lymphoma.

Patel: This is a very exciting year for acute lymphoblastic leukemia in general, specifically B-ALL. One of the concepts that excites me is using CD19[-targeted] CAR T-cell therapy as a consolidation therapy in patients who achieve remission. Historically, we’ve thought of CAR T-cell therapy as a [modality] to be used at the time of relapse or progression of B-ALL. There were 2 very exciting proof-of-concept studies that looked at the utilization of CD19[-targeted] CAR T-cell therapy once patients enter a remission, with the hope of more definitively offering a durable remission with a cellular therapy that’s not a transplant and is not long cycles of maintenance therapy or something like that. The concept of CAR T-cell therapy as consolidation is a very important one. Although these 2 studies showed promising efficacy rates with this approach, it’s still a little premature; [we’ll have] to see what the survival [data] will look like.

What were some of the key abstracts or topics of interest in chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL)?

Haddad: Number one is the [results from the phase 1 CARDINAL study (NCT06163430) of] TERN-701, an investigational drug for patients with relapsed/refractory CML that is also an allosteric [BCR::ABL1] inhibitor. [The agent] demonstrated safety and efficacy in a heavily pretreated population, so I’m glad to see positive results. Hopefully, this drug will move earlier in the lines of therapy and will offer newer options for our patients.

A second [area of interest] is the reports on the ASXL1 mutation and other additional genomic abnormalities in newly diagnosed CML. We know that these patients have a higher incidence of treatment failure and lower response rates. There are 2 key messages: Number one, [we should] always check for myeloid-type mutations like ASXL1 and others, in patients with newly diagnosed CML. Second, if they have this mutation, we need to monitor them closely for cytopenia and treatment failure response rates with a low threshold of modifying treatment if the patient is not achieving a good remission.

Andorsky: The plenary session this year actually has some pretty impactful abstracts [for CLL], including the [phase 3] CLL17 trial [NCT04608318] evaluating fixed-duration [ibrutinib (Imbruvica)] vs continuous targeted treatment with a BTK inhibitor. Findings from this study suggested that [a fixed-duration approach] is better.

Sharman: We’re seeing a lot of activity across a lot of diseases, blood cancers in particular. [For example,] we’re seeing the CLL17 study and some studies comparing pirtobrutinib [Jaypirca] with ibrutinib or even against bendamustine. There’s a lot to be seen in this space.

References

1. FDA approves epcoritamab-bysp for follicular lymphoma indications. FDA. November 18, 2025. Accessed December 18, 2025.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-epcoritamab-bysp-follicular-lymphoma-indications
2. FDA approves tafasitamab-cxix for relapsed or refractory follicular lymphoma. FDA. June 18, 2025. Accessed December 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tafasitamab-cxix-relapsed-or-refractory-follicular-lymphoma