Positioning CD19-Directed Therapies in the Greater Follicular Lymphoma Treatment Landscape

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

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

EP: 6.Patient Factors Influencing Follicular Lymphoma Treatment Sequencing

EP: 7.Updated Biosimilars Statement Anticipates Future Approvals

EP: 8.Using Prior Response and Repeat Biopsy to Guide Sequencing Strategy in Follicular Lymphoma

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EP: 9.Positioning CD19-Directed Therapies in the Greater Follicular Lymphoma Treatment Landscape

EP: 10.Emerging Therapies Reshaping Follicular Lymphoma Treatment

The introduction of CD19 as a major therapeutic target has complicated the treatment landscape for follicular lymphoma, challenging the long-standing dominance of CD20-directed agents. The most powerful CD19-directed treatment currently available is CAR T-cell therapy, but its high efficacy must be weighed against its associated short- and long-term toxicities. This creates a sequencing dilemma in an often-indolent disease.

The optimal position for these therapies depends on the aggressiveness of the patient's disease trajectory. Patients with a favorable history—such as those who achieve sequential, multi-year remissions after initial chemoimmunotherapy and subsequent anti-CD20 treatment—are generally not ideal candidates for immediate CAR T-cell therapy. Conversely, patients who experience early progression immediately after initial treatment are prime candidates for the earliest possible use of CAR T-cells due to their high-risk biology.

A primary concern in sequencing is preserving the CD19 target, ensuring that prior CD19-directed therapies do not "burn the bridge" by causing antigen loss. This risk is highlighted by observations in other drug classes: while CD20 loss is rare after standard rituximab, it is seen more frequently after potent CD20-targeting bispecific antibodies. Clinicians must remain vigilant, performing repeat biopsies to confirm CD19 expression and closely following the emerging literature. It is expected that the risk of CD19-negative variants may vary significantly among different CD19-directed agents, necessitating a data-driven approach to sequencing.