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

Summary for Physicians:

When determining if a patient with R/R FL is an appropriate candidate for CAR T therapies or bispecific antibodies, several factors should be considered, as follows:

1. Disease Characteristics:
   1. The patient should have R/R disease after standard therapies such as chemotherapy or targeted agents.
   2. Disease burden and the presence of high-risk features such as bulky disease or high-grade transformation can influence the decision to pursue CAR T or bispecific therapies.
2. Previous Treatment Responses:
   1. If a patient has previously responded well to therapies but then relapsed, CAR T may be a suitable next step, especially for those who have not responded to or are ineligible for other lines of treatment.
   2. Bispecific antibodies, which can offer a different mechanism of action, may be considered for patients who have not responded to other targeted therapies.
3. Patient Factors:
   1. The patient's performance status and overall health are crucial. For example, CAR T therapy requires a robust immune system and the ability to tolerate potential adverse effects such as cytokine release syndrome or neurotoxicity.
   2. Age and comorbidities should also be taken into account, as these can affect the patient’s ability to undergo the intensive processes involved with CAR T. In terms of CD20 status, a rebiopsy to assess CD20 expression can significantly impact treatment choices.

• CD20-positive: The majority of CAR T therapies and bispecific antibodies (eg, mosunetuzumab or blinatumomab) target CD20. For patients with CD20-positive disease, these therapies are appropriate and effective.
• CD20-negative: If the disease is CD20-negative on rebiopsy, it may not respond to therapies targeting CD20, including CAR T or bispecific antibodies. In such cases, other treatment strategies should be considered, such as alternative biologics or chemotherapy options that are effective in CD20-negative disease.

Ultimately, a personalized approach based on the patient's disease characteristics, prior treatments, performance status, and CD20 expression is key to deciding between CAR T therapies and bispecifics.