Sequencing Anti-CD19 Therapies in Follicular Lymphoma

EP: 1.The Clinical Utility of Updated Immunophenotyping Guidelines in Follicular Lymphoma

EP: 2.Challenges to NGS Testing for Follicular Lymphoma in the Community Setting

EP: 3.Data Supporting Tafasitamab, Lenalidomide, and Rituximab in Second-Line Follicular Lymphoma

EP: 4.Considering Third-Line Loncastuximab Tesirine Plus Rituximab in Follicular Lymphoma

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EP: 5.Sequencing Anti-CD19 Therapies in Follicular Lymphoma

EP: 6.Patient Factors Influencing Follicular Lymphoma Treatment Sequencing

Clinicians treating follicular lymphoma face a critical sequencing concern: whether prior CD19-directed therapies cause the loss or downregulation of the CD19 antigen, which is required for effective later-line treatments like CAR T-cell therapy to work.

This concern is rooted in the mechanism of action of targeted immunotherapy, where the therapeutic window relies entirely on the continued presence of the target. If early use of bispecifics or other CD19-targeting agents compromises this target, it effectively forecloses a critical, highly effective option down the line. Therefore, physicians must weigh the immediate benefit of a high-response-rate therapy against the risk of limiting future curative-intent approaches. Managing this balance is central to long-term disease planning.

Current clinical practice is hampered by a lack of mature, long-term data. Specifically, there is limited information from repeat biopsies on whether CD19 expression differs between patients who relapse early vs late after initial treatment. While preliminary findings are reassuring and suggest that widespread CD19 loss is not common, this data gap contributes to clinical reservation regarding the early use of these targeted agents in the second line.

However, the sequencing debate is not solely about antigen loss; it is also driven by comparative efficacy. Definitive results from ongoing phase 3 trials in follicular lymphoma will help determine the optimal strategy that maximizes both long-term disease control and the preservation of potential future treatment options like CAR T-cell therapy.