What are the effects of CAR-T (Chimeric Antigen Receptor T-cell) therapy after treatment with epcoritamab (Epcoritamab, a bispecific antibody)?

From the Guidelines

CAR-T therapy after epcoritamab is generally not recommended without careful consideration due to potential cumulative toxicities, and patients should typically wait at least 3-6 months before considering CAR-T therapy to allow for immune recovery. This waiting period is important because both therapies can cause significant immune-related adverse events, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) 1. The decision to proceed with CAR-T therapy after epcoritamab should be made by a multidisciplinary team with experience in cellular therapies, taking into account the patient's disease status, previous toxicities from epcoritamab, and overall fitness for further cellular therapy.

Some key considerations for patient eligibility for CAR-T therapy include:

• Age limit: no age limit, but decision should be based on physical condition rather than age 1
• Performance status: ECOG <2, Karnofsky >60% or Lansky >60% 1
• Life expectancy: >6-8 weeks, with careful consideration of risk-benefit ratio 1
• History of malignancy: absence of active malignancy requiring treatment other than non-melanoma skin cancer or carcinoma in situ 1
• Prior treatments directed toward antigenic target of CAR-T: not a contraindication, but antigen-negative escape should be excluded at relapse post-targeted therapy and before CAR-T 1

The specific CAR-T products that might be considered include axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), or lisocabtagene maraleucel (Breyanzi), depending on the underlying malignancy and previous response patterns. Bridging therapy may be needed during the waiting period to control disease progression. Patient monitoring before, during, and after CAR-T therapy is critical for early recognition of potential toxicities and timely intervention 1.

From the Research

Car-T Therapy After Epcoritamab

• Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells 2.
• In a phase I/II study, epcoritamab demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes, with an overall response rate of 63.1% and a complete response rate of 38.9% 2.
• A comparison of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy in third-line or later relapsed/refractory large B-cell lymphoma found no statistically significant differences in response rates or survival between epcoritamab and CAR T-cell therapy 3.
• CAR-T cell therapy is a breakthrough therapy for the management of different malignancies, including lymphomas and leukemias, with two CAR-T cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, approved by the US Food and Drug Administration 4.
• The use of epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL has shown promising results, with an overall response rate of 85% and a complete response rate of 61% 5.
• Axicabtagene ciloleucel, an anti-CD19 CAR T-cell therapy, has demonstrated efficacy in relapsed and refractory diffuse large B-cell lymphoma patients, but requires careful management of unique toxicities such as cytokine release syndrome and neurotoxicity 6.

Key Findings

• Epcoritamab has shown potent antitumor activity in relapsed or refractory large B-cell lymphoma.
• CAR-T cell therapy is a viable option for patients with relapsed or refractory large B-cell lymphoma.
• The combination of epcoritamab and GemOx has shown promising results in transplant-ineligible relapsed/refractory DLBCL.
• Careful management of toxicities is necessary when using CAR-T cell therapy.

Treatment Considerations

• Epcoritamab may be considered as a treatment option for patients with relapsed or refractory large B-cell lymphoma.
• CAR-T cell therapy may be considered as a treatment option for patients with relapsed or refractory large B-cell lymphoma, particularly those who have failed other treatments.
• The combination of epcoritamab and GemOx may be considered as a treatment option for transplant-ineligible relapsed/refractory DLBCL.