Latest Advances in Lymphoma and CLL Treatment: Insights from Dr Krish Patel

Krish Patel, MD, director of the Lymphoma Research Program at the Sarah Cannon Research Institute, recently shared significant updates from the American Society of Hematology (ASH) annual meeting, highlighting pivotal shifts in the treatment landscape for lymphoma and chronic lymphocytic leukemia (CLL). According to Patel, the field is moving rapidly beyond single-agent therapies toward more effective combination strategies and next-generation technologies.

A major theme of the meeting was the evolution of bispecific antibodies. While these agents have previously been utilized in later-line settings, new data is establishing their role in earlier treatment lines through combination therapies. Patel pointed specifically to abstract 0466, a phase 3 randomized trial that he describes as "practice-informing."

The trial evaluated epcoritamab (Epkinly) combined with lenalidomide (Revlimid) and rituximab (Rituxan) compared against the standard second-line regimen of lenalidomide and rituximab alone in patients with follicular lymphoma. Patel noted that the addition of epcoritamab resulted in impressive improvements in both response rates and progression-free survival (PFS). Although follow-up is still in the early stages, the data indicate a deeper quality of response favoring the triplet combination.

However, Patel cautioned that adding a third agent does introduce safety considerations. The trial noted an increase in adverse events, particularly late-onset infections, which clinicians will need to monitor closely as this combination moves toward standard practice.

In the realm of chronic lymphocytic leukemia (CLL), Patel highlighted the ongoing debate between fixed-duration therapy and continuous treatment. He discussed the CLL17 study, which compared continuous ibrutinib monotherapy against 2 fixed-duration combinations: venetoclax (Venclexta) plus obinutuzumab (Gazvya), and venetoclax plus ibrutinib (Imbruvica).

The study successfully met its primary end point, demonstrating noninferiority for the venetoclax-obinutuzumab combination. Patel emphasized that this is a "practice-affirming" result, providing evidence that patients can achieve outcomes with fixed-duration regimens that are comparable to continuous BTK inhibitor therapy. While subgroup analyses may reveal nuances later, the overarching message is that patients do not lose efficacy by opting for a time-limited treatment approach.

Looking toward the future, Patel expressed excitement about the next generation of CAR T-cell therapies. After nearly a decade of experience with current CAR T products, researchers are now presenting data on dual-antigen targeting CAR T cells—therapies designed to target 2 or more tumor proteins simultaneously. Early disclosures suggest these newer products may offer deeper responses and improved safety profiles compared to existing options. Head-to-head trials against approved CD19 CAR T cells in diffuse large B-cell lymphoma are currently underway.

Finally, Patel noted the growing "buzz" surrounding in vivo CAR T technology. A late-breaking abstract in myeloma served as a proof-of-principle that CAR T cells could potentially be generated directly inside the patient’s body. While the data is currently limited to a small number of patients, similar in vivo approaches are already under development for lymphoma, promising a potential paradigm shift in how cellular therapies are manufactured and delivered in the future.