Outpatient Treatment With Subcutaneous Epcoritamab Shows Feasibility in R/R DLBCL and Follicular Lymphoma

Findings from the phase 2 EPCORE NHL-6 trial (NCT05451810) showed the feasibility of administering subcutaneous epcoritamab-bysp (Epkinly) and monitoring for adverse effects (AEs) such as cytokine release syndrome (CRS) in an outpatient setting for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma.¹

Findings presented at the 2024 ASCO Annual Meeting showed that among 31 patients who received their first full dose of epcoritamab, 21 patients were treated entirely in the outpatient setting and did not require a hospital stay due to CRS or any other reason. Notably, 3 patients were treated in an inpatient setting due to AEs other than CRS, including pain management (n = 1), leg injury (n = 1), and urinary tract infection (n = 1). CRS occurred in 2 of these patients, who both had grade 1 events.

In the 28 patients monitored in the outpatient setting, CRS was reported in 10 patients at grade 1 (n = 6) of grade 2 (n = 4). Seven of these patients required subsequent inpatient management for CRS at the discretion of the physician.

“There [were] no discernible differences in the monitoring and management of CRS between academic and community sites in the study,” lead study author David J. Andorsky, MD, of Boulder Community Health and Rocky Mountain Cancer Centers, and colleagues wrote in a poster presentation of the data.

In May 2023, the FDA granted accelerated approval to epcoritamab for the treatment of adult patients with relapsed/refractory DLBCL not otherwise specified (NOS), including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma (HGBCL), after 2 or more lines of systemic therapies.² The regulatory agency then awarded accelerated approval to the bispecific antibody for the treatment of adult patients with relapsed/refractory follicular lymphoma following 2 or more lines of systemic therapy in June 2024.³ Both decisions were supported by data from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).

Bispecific antibodies such as epcoritamab are associated with unique AEs, including CRS and immune effector cell–associated neurotoxicity syndrome (ICANS), which often necessitate hospitalization. Transitioning to outpatient treatment could reduce health care costs and improve treatment accessibility, particularly for patients in community settings, study authors noted.¹

EPCORE NHL-6 enrolled patients at least 18 years of age with relapsed/refractory DLBCL— including DLBCL NOS and HGBCL—or grade 1, 2, or 3a follicular lymphoma. At least 1 prior line of treatment was required for patients with DLBCL, and those with follicular lymphoma needed to have 2 prior lines of therapy, including at least 1 anti-CD20 monoclonal antibody. All patients were required to have measurable disease and no central nervous system involvement. Those with well-controlled HIV were allowed to enroll.

Epcoritamab was administered in 28-day cycles and started with step-up doses of 0.16 mg on day 1 of cycle 1, followed by 0.8 mg on day 8 of cycle 1. The full dose of 48 mg was given on days 15 and 22 of cycle 1, once per week in cycles 2 and 3, biweekly in cycles 4 to 9, and once every 4 weeks from cycle 10 onward. Prior to data cutoff, a protocol amendment allowed for a third step-up dose of 3 mg for patients with follicular lymphoma; however, all patients included in this analysis received 2 step-up doses.

Treatment continued until progressive disease, intolerable toxicity, or patient withdrawal. All treated patients were followed for safety and survival.

Prior to each epcoritamab dose during cycle 1, patients received CRS prophylaxis with prednisone or dexamethasone; antipyretics; antihistamines; and hydration. Patients were allowed to leave the treatment facility on the same day as treatment, and they received a wallet card with information regarding the symptoms of CRS, ICANS, and clinical tumor lysis syndrome (CTLS). Patients were required to stay within 30 minutes of the treatment facility for at least 24 hours following the first full dose of the bispecific antibody.

In the outpatient setting, patients needed to record their temperature 3 times per day, and they were told to contact the treating physician if they experienced signs or symptoms of CRS. Inpatient management was then allowed if needed.

The primary objective of the study was to assess whether epcoritamab could be effectively monitored in an outpatient setting with reactive hospitalization vs prophylactic hospitalization.

At the data cutoff, 36 patients had received at least one dose of epcoritamab, including 23 with DLBCL and 13 with follicular lymphoma. The median age was 65 years (range, 28-86) for patients with DLBCL and 64 years (range, 52-72) for those with follicular lymphoma. Forty-eight percent and 54% of patients were less than 65 years of age, respectively. Forty-three percent of patients in the DLBCL cohort were female, and 54% of patients in the follicular lymphoma cohort were female. Thirty-six percent of enrolled patients were treated at an academic institution, and 64% were treated at a community site.

Patients with DLBCL had Ann Arbor stage II (95%), III (17%), or IV (74%) disease; and DLBCL (70%), double-hit lymphoma (22%), or triple-hit lymphoma (9%). Seventy percent of patients had de novo DLBCL, and 74% of patients had an ECOG performance status of 1. Revised International Prognostic Index scores included 0 (4%), 1 to 2 (30%), 3 to 5 (57%), and missing (9%). Seventy-four percent of patients had extranodal disease at screening, with disease sites including lung (30%), adrenal gland (22%), bone (17%), bone marrow (13%), and peritoneum (13%).

The median number of prior lines of therapy was 3 (range, 2-7) for patients with DLBCL; patients received 2 (39%), 3 (22%), or at least 4 (39%) prior lines of therapy. The median time from last prior anticancer therapy to first dose of epcoritamab was 3 months (range, 0-9). Forty-eight percent of patients received prior CAR T-cell therapy, and 35% were refractory to prior CAR T-cell therapy. Nine percent of patients underwent prior stem cell transplant. Sixty-five percent of patients were refractory to first-line therapy, including 35% who had no response and 30% whose disease relapsed within 6 months of completing therapy.

Patients with follicular lymphoma had an Ann Arbor stage of 1 (15%), II (8%), III (38%), or IV (38%). Most patients had an ECOG performance status of 0 (69%). Patients had a Follicular Lymphoma International Prognostic Index score of 0 (23%), 1 to 2 (23%), at least 3 (15%), or missing (38%). Fifty-four percent of patients had extranodal disease at screening with disease sites comprising lung (15%), adrenal gland (23%), bone (23%), bone marrow (15%), and peritoneum (15%).

Those with follicular lymphoma received a median of 4 prior lines of therapy (range, 2-7); number of prior lines of therapy included 2 (15%), 3 (23%), and at least 4 (62%). The median time from last prior anticancer therapy was 5 months (range, 1-42). Twenty-three percent of patients with follicular lymphoma received prior CAR T-cell therapy, and 15% were refractory to CAR T-cell therapy. Twenty-three percent of patients underwent prior stem cell transplant. Thirty-eight percent of patients were refractory to first-line therapy, including 15% who had no response and 23% whose disease relapsed within 6 months of completing treatment.

Among all treated patients (n = 36), the median duration of epcoritamab therapy was 2 months (range, 0.03-11), and the median number of cycles was 3 (range, 1-13). At data cutoff, 44% of patients remained on treatment. In the 56% of patients off treatment, primary reasons for discontinuation were progressive disease (22%), AEs (25%), patient withdrawal (6%), and other (3%).

Any-grade CRS was reported in 47% of all patients at grade 1 (25%), grade 2 (19%), and grade 3 (3%); no instances of grade 4 or higher CRS were reported. The median onset of CRS was 23 hours (range, 9-132). CRS resolved in 94% of all patients, and the median time to resolution was 3 days (range, 1-7). CRS interventions included tocilizumab (Actemra) alone (31%), corticosteroids alone (22%), or tocilizumab plus corticosteroids (11%). No patients discontinued epcoritamab due to CRS.

Any-grade ICANS occurred in 8% of all patients, all of whom had DLBCL. The rates of grade 1 and grade 2 ICANS were 6% and 3%, respectively; no grade 3 or higher ICANS events were reported. The median time to onset of ICANS after the first full dose of study drug was 62 hours (range, 16-109). ICANS resolved in all patients at a median time of 2 days (range, 1-6). No patients discontinued treatment due to ICANS. ICANS interventions included anticytokine therapy alone (3%), corticosteroids alone (6%), and anticytokine therapy plus corticosteroids (3%).

No instances of CTLS were reported.

“Enrollment [in EPCORE NHL-6] is ongoing, and a larger data set with cycle 1 optimization including hydration and dexamethasone will be presented [at a] later [date],” study authors concluded.

References

1. Andorsky D, Boccia R, Lash B, et al. Subcutaneous epcoritamab administered outpatient for relapsed or refractory diffuse large b-cell lymphoma and follicular lymphoma: results from phase 2 EPCORE NHL-6. J Clin Oncol. 2024;42(suppl 16):3515. doi:10.1200/JCO.2024.42.16_suppl.3515
2. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA. May 19, 2023. Accessed August 5, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell
3. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. FDA. June 26, 2024. Accessed August 5, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma