Optimizing Epcoritamab Therapy to Reduce CRS and ICANS Among Patients With R/R Follicular Lymphoma

First results from the EPCORE NHL-1 FL Cycle 1 Optimization Cohort

Julie Vose, MD, University of Nebraska Medical Center, Omaha, Nebraska, presents data from the EPCORE study, which explores improving the safety and clinical efficacy of CD3-CD20 bispecific antibody epcoritamab treatment administered strategically to reduce the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients with relapsed/refractory (R/R) follicular lymphoma (FL). This data includes first results from the fully enrolled EPCORE NHL-1 FL cycle 1 (C1) optimization (OPT) cohort.

“This abstract showed that these very simple measures can decrease cytokine release syndrome and (immune effector cell-associated neurotoxicity syndrome) ICANS and was very easily done [in the] outpatient [setting]. The majority of the patients were able to be administered outpatient without any subsequent hospitalization,” Dr Vose explained.  

This updated research was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:
 

Hi, I'm Dr Julie Vose from the University of Nebraska Medical Center, and it was my pleasure to present an update on the epcoritamab study for relapsed/refractory follicular lymphoma at ASCO 2024.

This abstract focused on patients in the cycle 1 optimization cohort for the EPCORE study. This is a CD3-CD20 bispecific antibody for treatment of follicular lymphoma in this case. This particular cohort was to try to optimize the premedication in cycle 1 to decrease the cytokine release syndrome (CRS) and neurologic toxicity to see if it is a better fit for patients with follicular lymphoma who are getting this treatment, and hopefully try to do it in an outpatient basis. The cycle 1 optimization included an additional step-up dosing to 3 step-up dosing as compared to 2 in the previous cohort.

In addition, patients in this cohort had prophylaxis with dexamethasone, 15 mg, prior to each step-up dosing and to the full dose at the 4^th dose, as well as intravenous hydration. Outpatient hospitalization was optional, which was different than the prior cohort as well.

For this particular study, what was found in the patient characteristics, these were all patients who were the same as in the pivotal cohort: Median age is about 63, advanced stage, high IPI [Follicular Lymphoma International Prognostic Index] (FLIPI) clinical cohort, patients had received multiple prior therapies, and were higher risk. This is the same as the prior cohort.

The patients, as far as the treatment adverse events in the cycle 1 optimization cohort with the additional measures we just talked about, had a decrease in cytokine release syndrome, and there was no grade 3 cytokine release syndrome as compared to what was seen in the prior cohort. In addition, there was no neurologic toxicity in the patients in this cohort as compared to a small percentage in the prior cohort.

It was felt that this was able to be utilized with these simple measures to try to decrease the cytokine release syndrome and neurologic toxicity of this particular agent in follicular lymphoma patients. In addition, the interleukin-6 (IL-6) levels were measured after cycle 1 and were found to be lower in the patients with this step-up dosing, which was consistent with the lower rates of CRS and neurologic toxicity.

Response rates, at least at this time as the shorter follow-up, still are very high with overall response rates of 86% compared to 83% in the prior cohort. In addition, the (complete response rate) [CRR] was 64% compared to 66% in the prior cohort, so [there was] no detriment to the response rate with these additional measures to try to decrease toxicity. Minimal residual disease (MRD) was also measured, and in the 2 courts together, patients with minimal residual disease negative at any time point had a much better PFS as compared to those patients with positive MRD and specifically the cycle 3, day 1 landmark had a much higher outcome with PFS if they were negative by MRD as compared to the not negative MRD landmark cycle 3, day 1.

In conclusion, this abstract really showed that these very simple measures can decrease cytokine release syndrome and (immune effector cell-associated neurotoxicity syndrome) ICANS and was very easily done [in the] outpatient [setting]. The majority of the patients were able to be administered outpatient without any subsequent hospitalization. Hopefully this will be looked at, and the date for epcoritamab in relapsed or refractory follicular lymphoma has a target date of June 28, 2024. Thank you.

Source:

Vose J, Vitolo U, Lugtenburg P, et al. EPCORE NHL‑1 follicular lymphoma (FL) cycle (C) 1 optimization (OPT) cohort: Expanding the clinical utility of epcoritamab in relapsed or refractory (R/R) FL. Presented at the ASCO Annual Meeting. May 31–June 4, 2024; Chicago, IL. Abstract 7015