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The phase 3 INMIND trial showed adding tofacitimab to lenalidomide and rituximab (R-squared) significantly improves progression-free survival over R-squared alone. This fixed-duration regimen with a manageable toxicity profile is now considered a new standard of care for this patient population, including high-risk subsets.
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The phase 3 EPCOR FL-1 trial showed that adding epcoritamab to the lenalidomide/rituximab (R-squared) backbone profoundly improved progression-free survival in relapsed follicular lymphoma. Presented as the most important FL abstract at ASH, this result is expected to establish a new standard of care in this setting.
When choosing a bispecific antibody for follicular lymphoma, a major practical difference is the treatment duration. Mosunetuzumab is a time-limited therapy stopped after achieving a complete response, while Epcoritamab is given indefinitely until progression. This distinction heavily influences selection, especially for elderly patients.
A novel trial design used mosinutuzumab monotherapy first in frontline follicular lymphoma, adding lenalidomide only for patients without a complete response. This adaptive approach successfully spared about two-thirds of patients from the added toxicities of lenalidomide while still achieving very high overall efficacy.
The Rosewood study shows the combination of zanubrutinib and obinutuzumab is highly effective in high-risk, relapsed/refractory follicular lymphoma. This is a significant finding because BTK inhibitors as a class have historically shown minimal activity in this disease, suggesting this specific combination creates a new therapeutic opportunity.
In follicular lymphoma, the treatment goal is durable remission with manageable toxicity, not necessarily a cure. Therefore, clinicians frequently prefer using a bispecific antibody first, reserving the more complex and toxic CAR-T cell therapy for transformed disease or after a bispecific fails.
When choosing between novel combinations in relapsed follicular lymphoma, a logical strategy is to use tafasitamab-lenalidomide-rituximab (Tafa-R2) first. After progression, single-agent epcoritamab remains highly effective. The reverse is not true, as tafasitamab monotherapy would not be effective after epcoritamab-R2 failure, making the initial choice critical.
Despite new therapies for follicular lymphoma (FL), bendamustine-rituximab (BR) will likely remain the community standard due to its simplicity. This may create a growing gap in treatment approaches between academic centers using novel agents and community practices favoring the familiar BR regimen.
A key clinical concern with CD19-directed therapies is antigen loss, which could prevent future CAR T-cell treatments. Data from the INMIND trial alleviates this fear, showing that 23 of 24 post-treatment lymphoma samples retained CD19 expression, suggesting tofacitimab does not preclude subsequent CAR-T therapy.
In the IN-MIND trial for relapsed follicular lymphoma, the tafasitamab-lenalidomide-rituximab arm had zero cases of histologic transformation to a more aggressive lymphoma. This contrasts with nine cases in the control arm, suggesting the CD19-targeting antibody may eradicate precursor cells responsible for this dreaded complication.
The dramatic efficacy boost from adding epcoritamab suggests it's the primary driver of patient benefit, not just an adjunct. This shifts the conceptual framework, positioning the bispecific antibody as the new therapeutic backbone, with rituximab and lenalidomide as supportive agents.
