Epcoritamab Optimization Lowers Neurotoxicity, Boosts Outpatient Feasibility in Follicular Lymphoma

Julie M. Vose, MD, MBA

Introducing simple adjustments to the administration of epcoritamab-bysp (Epkinly), such as prophylactic dexamethasone, hydration, and selectively withholding antihypertensives, has been shown to enhance patient safety and treatment tolerability, thereby indicating the feasibility of considering epcoritamab as an outpatient treatment option for patients with relapsed/refractory follicular lymphoma (FL), according to Julie M. Vose, MD, MBA.

Results from the FL cycle 1 optimization cohort (FL C1 OPT; n = 86) of the phase 1/2 EPCORE NHL-1 trial (Study GCT3013-01; NCT03625037) were presented at the 2024 ASCO Annual Meeting and showed that the 3 step-up doses of this regimen with these measures reduced the incidence and severity of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome. The overall incidence of CRS was 66% vs 49% in the pivotal (n = 128) vs FL C1 OPT cohorts, respectively. Overall, 24% vs 12% of patients were given tocilizumab (Actemra) in these respective arms, and both cohorts had a 100% CRS resolution rate. Moreover, response rates, minimal residual disease–negativity rates, and time to complete response (CR) were consistent between the pivotal and FL C1 OPT cohort.

“[These measures] remarkably reduced the incidence of CRS, eliminated grade 3 adverse effects [AEs], and patients had no neurologic toxicity as compared with the prior study,” said Vose in an interview with OncLive^®.

Based on efficacy data from EPCORE NHL-1, the FDA granted accelerated approval to epcoritamab for the treatment of adult patients with relapsed or refractory FL following 2 or more lines of systemic therapy. In the primary efficacy population (n = 127), epcoritamab elicited an overall response rate (ORR) of 82% (95% CI, 74.1%-88.2%), comprising a CR rate of 60% (95% CI, 50.8%-68.4%) and a partial response rate of 22% (95% CI, 15.2%-30.3%).²

In the interview, Vose discussed the goal of evaluating these adjustments to epcoritamab administration in relapsed/refractory FL, detailed how these measures enhanced the safety of epcoritamab in the FL C1 OPT cohort of EPCORE-NHL-1, and expanded on the potential impact of these approaches on both drug tolerability and financial burden.

Vose serves as the division chief, the Neumann M. and Mildred E. Harris Professor, and a physician in the Division of Hematology and Oncology at the University of Nebraska Medical Center in Omaha, Nebraska. She is also a recipient of the 2022 Giants of Cancer Care^® award for lymphoma.

OncLive: What was the rationale for evaluating a dose-optimization protocol for epcoritamab in patients with relapsed/refractory FL?

Vose: The idea behind the EPCORE-NHL FL C1 OPT cohort was to see whether we could reduce the CRS and neurologic toxicity associated with epcoritamab, specifically for patients with FL, by [using] some simple measures. [These included] administering dexamethasone prior to each of the first several doses in the outpatient setting, and by giving 500 CCs to 1 liter of normal saline for hydration prior to that. For example, some of the patients had their antihypertensives held if appropriate, and the patients were able to be treated in the outpatient setting, for the most part.

What key safety findings from this cohort were reported?

[At the 2024 ASCO Annual Meeting], I presented these new findings with the added measures, and the [data] were compared [with results from patients with FL from] the prior study, which did not have that optimization cohort. The big safety findings we talked about were CRS. Overall, there was less CRS in the updated optimized cohort, and there was no grade 3 CRS at all. Additionally, there was no neurotoxicity in the updated cohort as compared with a small percentage in the prior cohort. Those 2 findings were big. Also, hospitalization was optional in this new cohort, whereas in the prior cohort, it was required for the full third dose. Many of these patients [in the FL C1 OPT cohort] were able to be treated completely outpatient.

How did the efficacy of this optimized approach compare with that of the non-optimized approach from the prior FL cohort in EPCORE NHL-1?

Efficacy from the cohort was also presented and compared with the prior cohort. The ORR was [86% in the FL C1 OPT cohort], and the CR rate was 64%. It was pretty much the same as the prior cohort. The newer cohort had less follow-up compared with the older cohort, though we are continuing to assess responses over time. At this time, there was essentially no difference [between the 2 cohorts] as far as response rates.

Given the recent FDA approval of epcoritamab in relapsed/refractory FL, what are the implications of this research? What still needs to be learned to improve results with epcoritamab in practice?

Trying to see whether we can use these optimized measures going forward will be important. [The FDA does not] mandate hospitalization for the full dose [for patients with FL]. It’s important to see that we can reduce some of these AEs by simple measures that don’t cost a lot of money. If we can keep the patients in an outpatient setting, it will reduce overall health care costs. [These findings have] big implications.

References

1. 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. J Clin Oncol. 2024; 42(suppl 16):7015. doi:10.1200/JCO.2024.42.16_suppl.7015
2. Epkinly. Prescribing information. Genmab; 2024. Accessed August 5, 2024. https://www.genmab-pi.com/prescribing-information/epkinly-pi.pdf