Epcoritamab Plus Rituximab/Lenalidomide Produces Responses in High-risk R/R Follicular Lymphoma

Reid W. Merryman, MD

Treatment with the combination of epcoritamab-bysp (Epkinly), rituximab (Rituxan), and lenalidomide (Revlimid [R2]) led to responses and durable remissions in patients with relapsed/refractory follicular lymphoma (R/R FL), including in those who progressed within 24 months of first-line chemoimmunotherapy (POD24) and other high-risk features.

At the 2023 ASCO Annual Meeting, a pooled analysis from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE NHL-2 trial (NCT04663347) was presented by Reid W. Merryman, MD. EPCORE NHL-2 is investigating the T-cell engager bispecific antibody epcoritamab in different combinations for patients with B-cell non-Hodgkin lymphoma, and cohorts 2a and 2b are specifically for patients with R/R FL receiving epcoritamab subcutaneous (SC) plus R2.

“The addition of epcoritamab to R2 leads to deep and so far, quite durable remissions in [R/R FL], including POD24 patients and other high-risk populations. High overall and complete response rates were observed across all different patient subgroups,” Merryman, lead author, physician at Dana-Farber Cancer Institute, and instructor of medicine at Harvard Medical School said in his presentation.

There were poor outcomes in POD24 patients, and those who are double refractory to an anti-CD20 monoclonal antibody and an alkylating agent. Currently, there is no definitive standard of care and overall survival for these patients is inferior to those who were not POD24.

Therapies like T-cell­ engagers have demonstrated improved results for patients with R/R FL and high-risk features, but outcomes remain suboptimal in this patient population, according to Merryman. Epcoritamab SC showed durable responses and manageable safety in the EPCORE NHL-1 trial (NCT03625037), leading to its approval for patients with certain R/R B-cell non-Hodgkin lymphomas after 2 or more lines of systemic therapy.

In the 104 efficacy evaluable patients treated with epcoritamab at 48 mg plus R2, the overall response rate (ORR) was 98% and ORR to the immediate prior therapy was 85% at the data cutoff of January 31, 2023 (median follow-up, 11.4 months). The complete metabolic response (CMR) was 87% and 58% for current therapy with epcoritamab and immediate prior therapy, respectively. Partial metabolic response (PMR) was 12% and 27%, stable disease 1% and 5%, and progressive disease 1% and 7%, in each arm.

Across subgroups, high ORR and CMR rates were also observed, with 95% or greater ORR in all groups. There was 75.0% CMR and 22.5% PMR for POD24 patients (n = 40), and a 98% ORR in this group. In primary refractory patients (n = 37), 83.8% and 16.2% had CMR and PMR, respectively. There was a CMR/PMR of 80.9%/14.9% in patients refractory to prior anti-CD20 (n = 47), 75.7%/18.9% for those who were double refractory (n = 37), 86.7%/11.7% in those with high Follicular Lymphoma International Prognostic Index (FLIPI), and 90.0%/10.0% for those with non–high-risk disease.

The ORR for patients with and without POD24 receiving epcoritamab was identical, at 98%. For POD24 patients receiving study treatment in the second line, the ORR was 100% and CMR was 86%. In the third line or later, the ORR was 85% and CMR was 63% for POD24 patients.

Additionally, the median time to response was 1.4 months; this was the same for POD24 and non–POD24 patients.

“The 1-year duration of complete response was 89% for the overall population and 90% for POD24 patients,” Merryman said. “The progression-free survival [PFS] curves look quite similar given the high response rates. Again, the curves for the overall population and POD24 patients are similar. The 1-year PFS [rate was] 78%.”

In the safety analysis, 111 patients were evaluable from cohorts 2a and 2b of EPCORE NHL-2 and findings were consistent with previous reports. Treatment-emergent adverse events (TEAEs) of grade 3 or more were seen in 76% of patients, and 41% were related to epcoritamab SC. Immune effector cell-associated neurotoxicity syndrome was seen in 2% and the median time to resolution was 5.5 days (range, 4-7).

Delays due to a TEAE were needed in 61% of patients with 29% related to epcoritamab SC. Thirteen percent of patients discontinued epcoritamab SC, 5% due to epcoritamab SC, and there were 4 fatal TEAE events all due to COVID-19.

Cytokine release syndrome (CRS) events were explored further in the analysis, which showed CRS occurrence was predictable. A majority of the events were low grade (grade 1, 34%; grade 2, 12%; grade 3, 2%), and all events were resolved. The median time to resolution was 3 days (range, 1-23), and 13% of patients were treated with tocilizumab. No patients discontinued epcoritamab SC due to CRS.

In EPCORE NHL-2, patients enrolled must have stage II, II, or IV R/R CD20 FL of grade 1, 2, or 3A. Moreover, they needed an ECOG performance status of 0 to 2, measurable disease by CT or MRI, and adequate organ function. The primary objectives include antitumor activity and safety.

The baseline characteristics of cohort 2a and 2b showed the median age was 65 years (range, 30-80) and half the population were female patients. Sixty percent of patients had Ann Arbor stage IV and 58% had FLIPI score 3 to 5 disease. The majority also had an ECOG performance status of 0 and no bone marrow involvement. There were 29% who had larger than 7 cm of bulky disease.

For these patients, the median time from diagnosis to first dose of epcoritamab was 63 months (range, 4-331), and median time from the end of their last line of therapy to their first dose was 17 months (range, 0.6-213). Most patients on the trial had 1 prior line of therapy (57%), but some had 2 (25%) or 3 or more prior lines (18%). All patients received prior anti-CD20 therapy, 93% received alkylating agents, 64% received anthracyclines, 8% received PI3K inhibition, 5% received immunomodulatory inhibitor drugs, and 2% received chimeric antigen receptor T-cell therapy.

As of the data cutoff for the pooled analysis, 73% of patients continued to receive epcoritamab SC plus R2. There was a median of 10 treatment cycles initiated (range, 1-25), and the median duration of treatment was 9 months (range, 0.3-22).

“Based on these encouraging results, epcoritamab-based combinations are being studied in an ongoing, randomized phase 3 trial, the EPCORE FL-1 trial [NCT05409066], as well as in a non-randomized POD24 cohort in the EPCORE NHL-2 trial,” Merryman concluded.

Reference

Merryman R, Belada D, Sureda A, et al. Epcoritamab + R2 regimen and responses in high-risk follicular lymphoma, regardless of POD24 status. J Clin Oncol. 2023;41(suppl 16):7506. doi:10.1200/JCO.2023.41.16_suppl.7506