Authored by Dr. Brian Koffman
Bottom Line:
Epcoritamab, a novel subcutaneous (an under-the-skin injection) CD3xCD20 bispecific antibody, resulted in a 62% response rate in high-risk, difficult-to-treat relapsed or refractory (R/R) CLL patients that so far appears to be durable.
Who Performed the Research and Where Was it Presented:
Dr. Arnon Kater, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, Netherlands, presented the results at iwCLL 2023 (international workshop on CLL) in Boston, MA.
Background:
Despite the progress in CLL therapies, new therapies are needed for patients for whom Bruton’s tyrosine kinase inhibitors (BTKi) and venetoclax have failed. These patients are often difficult to treat with high-risk prognostic markers, including TP53 aberrations and/or unmutated IGHV. Epcoritamab is a novel subcutaneous (SC) bispecific T cell engaging (BITE) monoclonal antibody that binds to CD3 on the surface of T cells, and CD20 found on CLL and normal B-cells, bringing the T cell next to the targeted CLL cells marked for destruction. As such, it is an immune therapy similar to CAR-T but is available “off the shelf” and is not made up of cells but antibodies. The FDA has already approved it for R/R diffuse large B-cell lymphoma (DLBCL). The EPCORE CLL-1 study presented at ASH 2021 showed encouraging efficacy and manageable safety in R/R CLL and Richter’s syndrome. These data are the results of an expansion of that trial.
Methods and Participants:
Twenty-three patients were enrolled. The average age was 72, and 74% were males. 70% were IGHV unmutated, and 65% were TP53 aberrant. Patients averaged four prior lines of therapy. All patients had been treated with a BTKi and prior chemotherapy, and 83% had a BCL-2 such as venetoclax. They are a tough group to treat.
Epcoritamab was ramped up over three weeks to its full dose of 48 mg given SC and given with steroid prophylaxis for cytokine release syndrome (CRS), commonly seen in immune therapies. Shots were infused weekly x 12, then biweekly for another 12 doses, and then every four weeks until intolerance progression. The primary endpoint was the overall response rate (ORR), but complete response (CR), time to response, and safety and tolerability were also studied.
Results:
- Adverse events:
- 100% had CRS, with most being grade 2 (73.9), but there were no grade 4 CRS or CRS-related deaths. 100% had CRS with the first full-strength dose of 48 mg, but it was not uncommon to be seen at other doses and to be recurrent.
- Other common adverse events (AE) were:
- Low platelets (60.1%)
- Anemia (56.5%)
- Low neutrophils (39.1)
- Edema or swelling (47.8%)
- Diarrhea (43.4%)
- Fatigue (43.4%)
- Pneumonia (30.4%), including one treatment-related death.
- Most AEs were mild.
- There were three deaths: 2 from pneumonia, though only one was considered treatment, and one from squamous cell carcinoma of the skin.
- Results:
- Overall responses were seen in 13 patients (62%)
- Complete responses were seen in 7 patients (33%)
- Partial responses were found in 6 patients (29%)
- Stable disease was the outcome in 4 patients (19%)
- Only one patient (5%) had progressive disease.
- Response rates were similar regardless of the patient’s risk characteristics
- The median time to respond was 1.9 months, and to CR was only 3.6 months.
Conclusions:
In a difficult-to-treat, high-risk population of patients with R/R CLL, most of whom had been double-exposed, epcoritamab SC showed encouraging activity.
Responses were seen quickly and often (ORR 62%; CR rate 33%) and appear durable, with an estimated 83% of responders remaining in response at nine months, the length of the follow-up.
Safety was manageable, and what is expected with T-cell–engaging strategies; there were no new safety worries discovered. CRS events were seen in all patients but were mostly low-grade; all were relatively short-lived, and despite being unpleasant to go through, none led to discontinuation. Epcoritamab seems like a promising new option for patients with few options.
Links and Resources:
Watch Dr. Brian Koffman’s monologue on the abstract:
Stay strong. We are all in this together.
Brian Koffman MDCM (retired), MS Ed
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society
