Authored by Dr. Brian Koffman
Bottom Line:
Epcoritamab, a bispecific antibody, led to a 50% overall and 35% complete response rate in all Richter’s transformation patients.
Who Performed the Research and Where Was it Presented:
Dr. Arnon Kater from the U. of Amsterdam in the Netherlands gave an oral presentation on behalf of an international coalition of researchers on the last day of colleagues at the 2024 European Hematology Association (EHA) Annual Meeting in Madrid.
Background:
Richter’s transformation (RT), also called Richter’s syndrome, is when chronic lymphocytic leukemia (CLL) transforms into a more aggressive lymphoma, usually CD20 + DLBCL (diffuse large B-cell lymphoma), and carries a dismal prognosis with complete response (CR) rates less than 20% with conventional therapies. Epcoritamab is a CD3xCD20 bispecific antibody administered subcutaneously that is already approved for the treatment of adults with different subtypes of relapsed or refractory (R/R) large B-cell lymphoma after ≥2 lines of systemic therapy in several countries, including the USA. It is a powerful immunotherapy that engages the T cells and directs them to attack any CD20+ cells, including CD20 + RT cells. The ongoing phase 1b/2 EPCORETM CLL1 trial is assessing the safety and efficacy of epcoritamab in CLL and RT. At the 2024 EHA Annual Meeting, the first data from a larger population with longer follow-ups was presented.
Methods and Participants:
Adults with biopsy-proven transformation to CD20+ DLBCL and a clinical history of CLL or small lymphocytic lymphoma (SLL) with ≤2 prior lines of treatment for their large B-cell lymphoma for RT received epcoritamab 48 mg in 28-day cycles until disease progression. Epcoritamab was slowly ramped up over several weeks, and steroids were used to lower the risk of CRS (cytokine release syndrome) with this potent immunotherapy. This is similar to the CRS seen with CAR-T, which also involves activated T cells.
Results:
- 35 pts with RT had received epcoritamab.
- A total of 91% of pts had ≥1 prior treatment line for CLL or RT.
- 49% had prior treatment for RT.
- Most pts (57%) had received a Bruton’s tyrosine kinase (BTK) or B-cell lymphoma 2 (BCL2) inhibitor before transformation,
- The most common prior treatment for RT was an anti-CD20 monoclonal antibody–containing chemo-immunotherapy or CIT regimen, primarily R-CHOP (in 76% of patients with previous treatment).
Adverse Events (AE):
- The most common nonhematologic treatment-emergent adverse events (TEAE) was CRS (80%).
- Thrombocytopenia (low platelets) and anemia were observed in 40% of pts each at baseline and in 40% and 34% of patients, respectively.
- CRS events primarily occurred following the first full dose, and most were low grade; only one patient (3%) had Grade 3 or serious CRS.
- Four patients had immune effector cell-associated neurotoxicity syndrome or ICANS (Grade1, n=2; Grade2, n=2); all four patients had concurrent CRS.
- Clinical tumor lysis syndrome (CTLS) occurred in 3 pts (G1–3, n=1 each). No CRS, ICANS, or CTLS events led to tx discontinuation.
- Two patients discontinued treatment due to AEs, and 3 pts had fatal TEAEs (general physical health deterioration in 2 and sepsis in 1).
Responses:
- 13 pts (37%) were still receiving epcoritamab.
- In the response-evaluable population of 26, the overall response rate (ORR) was 50%, and the CR rate was 35%.
- For those for whom epcoritamab was their first treatment for RT, the ORR was 62%, and the CR was 54%
- Median times to response and CR were short (1.4 mo and 2.4 mo, respectively)
- 53% of patients with CR remained in CR at 9 mo (75% among patients with CR without prior treatment for RT).
Discussion and Conclusion:
With half the patients responding and over a third reaching a CR, with more than ½ of those still in remission nine months later, these are encouraging results in a disease where most patients don’t live longer than a year. The results are even better when it is used as frontline therapy for RT, suggesting future ethical trial design should allow its use without forcing patients first to fail a toxic and usually ineffective CIT. It’s early, but appropriate dosing, ramp-up, CRS prophylaxis, and possible combinations with other medications to enhance its efficacy should be included in future research. This is a potent immune therapy that is not easy and not without its risks, but it can be managed in a disease that is often fatal within months.
Links
Listen to my monologue below.
Read the abstract at: SINGLE-AGENT EPCORITAMAB LEADS TO DEEP RESPONSES IN PATIENTS (PTS) WITH RICHTER’S TRANSFORMATION (RT): PRIMARY RESULTS FROM THE EPCORE CLL-1 TRIAL
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-founder, Executive VP and Chief Medical Officer
CLL Society, Inc.
