Dr Goy on the Expanding Role of Combinations and CAR T-Cell Therapy in High-Risk Mantle Cell Lymphoma

“We have seen a trend toward the activity of biologic agents, including single [agents], doublets, and triplets now. There are several studies [evaluating] combinations with venetoclax, BTK inhibitors, and anti-CD20 [antibodies] that have showed very impressive response [rates], including in high-risk patients. Given that the median age at diagnosis is in the mid-to-late 60s and [many] patients are not eligible for intensive regimens, [these approaches appear] promising.”

Andre Henri Goy, MD, physician in chief of Hackensack Meridian Health Oncology Care Transformation Services; chairman and chief physician officer of John Theurer Cancer Center at Hackensack University Medical Center; and Lymphoma Division chief at John Theurer Cancer Center, summarized key developments in mantle cell lymphoma (MCL) presented at the 2025 ASH Annual Meeting and Exposition, with particular emphasis on strategies for patients with high-risk disease.

According to Goy, a major theme at ASH 2025 was the continued shift away from intensive chemoimmunotherapy regimens toward biologically driven and targeted approaches, particularly for patients with high-risk features or aggressive disease biology. He explained that these patients have historically had poorer outcomes with conventional chemotherapy, underscoring the need for alternative frontline and relapsed/refractory strategies. Goy noted that studies evaluating single-agent, doublet, and triplet biologic regimens—incorporating treatments such as anti-CD20 antibodies, BTK inhibitors, and BCL2 inhibitors—have shown encouraging activity, even in these high-risk populations.

The high overall response rates and deep remissions, including high complete response rates, observed with these combinations in patients with adverse prognostic features are notable, Goy said. He added that that these findings are particularly relevant given that the median age at diagnosis for patients with MCL is in the mid-to-late 60s, making many patients ineligible for intensive induction regimens or autologous stem cell transplant.

Another notable area of progress in the induction setting was the incorporation of bispecific antibodies into targeted therapy backbones, Goy said. Data from the phase 2 GLOVe trial (NCT05861050) evaluating glofitamab-gxbm (Columvi), a CD20×CD3 bispecific antibody, in combination with venetoclax (Venclexta) and lenalidomide (Revlimid) displayed efficacy signals in MCL. Although follow-up remains limited, these results suggest that T-cell–engaging strategies may further deepen responses when added to biologic regimens and could expand treatment options for patients who are unfit for aggressive therapy.

Updates on CAR T-cell therapy were also featured prominently at ASH 2025, Goy continued. Longer-term follow-up with brexucabtagene autoleucel (Tecartus) continued to demonstrate that a subset of patients with relapsed or refractory MCL can achieve durable, long-term remissions. Although late-onset toxicities remain an important consideration, these data reinforce the role of CAR T-cell therapy as a transformative option rather than a niche treatment for select patients, Goy concluded.