Managing R/R FL: Evolving Sequencing Strategies

EP: 1.Overview of R/R FL: Focus on the 3rd-Line Setting and Beyond START

EP: 2.Managing 3rd-Line R/R FL: Recognizing Progression, Performing Rebiopsies, and Rechecking for CD20 Positivity

EP: 3.Aligning Treatment Goals in R/R FL: Physician vs Patient Perspectives

EP: 4.Clinical Scenario: A 73-Year-Old Patient With R/R FL Requires Treatment in the Third-Line Setting

EP: 5.Expert Perspectives: Tazemetostat in R/R FL

EP: 6.Choosing Between Tazemetostat and Zanubrutinib+Obinutuzumab: Key Factors & Patient Conversations

EP: 7.Assessing CAR T and Bispecifics for R/R FL: Identifying the Right Candidates & Factoring in CD20 and CD19 Negativity or Positivity

EP: 8.Navigating Treatment Choices in R/R FL: Patient Values and Shared Decision-Making

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EP: 9.Managing R/R FL: Evolving Sequencing Strategies

EP: 10.Key Strategies and Perspectives: How Novel 2nd-Line Therapy Options May Impact 3rd-Line Treatment Landscape in R/R FL and Bridging Strategies to CAR T

Summary for Physicians:

Sequencing of CAR T, Bispecifics, EZH2 Inhibitors, Loncastuximab, and BTK Inhibitors:

When sequencing treatments for relapsed/refractory patients, several factors influence the decision to choose between CAR T therapies, bispecific antibodies, EZH2 inhibitors, loncastuximab, and Bruton tyrosine kinase (BTK) inhibitors, as follows:

1. Disease Characteristics:
   1. CAR T therapies are typically considered for patients with high disease burden or large cell transformation, particularly when other therapies have failed.
   2. Bispecific antibodies are an option for patients who might not be suitable for CAR T therapies or those preferring more flexible, outpatient options. Bispecifics, such as mosunetuzumab, are useful for relapsed patients.
2. Prior Treatments:
   1. EZH2 inhibitors (such as tazemetostat) are considered for patients with EZH2 mutations, especially when other treatments have not been effective.
   2. Loncastuximab is often used in CD19-positive relapsed/refractory disease, especially in diffuse large B-cell lymphoma or mantle cell lymphoma (MCL), when CAR T is not an option.
   3. BTK inhibitors (such as ibrutinib andacalabrutinib) are typically used for patients with chronic lymphocytic leukemia or MCL, offering oral therapies for long-term disease management.
3. Patient Factors:
   1. The patient's performance status, comorbidities, and personal preferences (such as a preference for oral therapy or avoiding infusions) are crucial in treatment decision-making. Patients with poor performance status may benefit more from oral agents such as BTK inhibitors.
   2. Adverse effect profiles are also critical in decision-making, as CAR T therapies can result in severe reactions such as cytokine release syndrome, influencing the choice of therapy.

Ultimately, treatment sequencing should be personalized, balancing efficacy, patient preferences, and tolerability to achieve the best outcomes in relapsed/refractory lymphoma.