Reid Merryman, MD, on High-Risk Follicular Lymphoma: New Data on Epcoritamab, Rituximab, and Lenalidomide
2023 ASCO Annual Meeting
Reid Merryman, MD, of Dana-Farber Cancer Institute, discusses his findings on the regimen of epcoritamab plus rituximab and lenalidomide for patients with high-risk follicular lymphoma. Regardless of whether their disease progressed within 24 months of first-line chemoimmunotherapy, this regimen showed antitumor activity and a manageable safety profile in patients with relapsed or refractory disease. Epcoritamab, a subcutaneous T-cell–engaging bispecific antibody, may abrogate the negative effects of high-risk features (Abstract 7506).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
At ASCO this year I presented updated results from Epcoritamab plus R2 for patients with relapsed or refractory follicular lymphoma. Each of those three drugs, rituximab, lenalidomide, and epcoritamab, has different modes of action. It was hypothesized that lenalidomide with its immunomodulatory properties might enhance the activity of epcoritamab.
In this study, patients received R2 over 12 cycles using standard dosing and two different doses of epcoritamab were tested, two different dose schedules. In arm 2A, patients received more frequent epcoritamab dosing, dosed weekly for the first three cycles, every two weeks for cycles four through seven, and every four weeks thereafter. Whereas an arm 2B, less frequent epcoritamab dosing was used every week for the first two cycles, and every four weeks thereafter.
In total 111 patients were treated and they had received a median of one prior line of therapy. Notably, patients had many high risk features in this cohort. Approximately 60% of patients had Stage 4 disease. About 40% of patients had progression of disease within the first two years of chemoimmunotherapy treatment, so-called POD24 patients, and approximately 60% of patients had a high risk FLIPI score.
The safety profile for this combination was similar to previous reports. The most common side effects included cytokine release syndrome, infections, and neutropenia. CRS was seen in about half of patients, but was primarily low grade with only 2% of patients having Grade 3 or higher CRS. CRS occurred over a predictable timeline. Almost all CRS occurred over the first two cycles, and most CRS occurred after the first full dose of epcoritamab, which was given on cycle one, day 15. Notably, CRS resolved in all patients and no patients discontinued epcoritamab based on cytokine release syndrome.
Among all patients the overall response rate was 98%, and the complete metabolic response rate was 87%, both of which are very high for this disease setting. Notably, all patients did well, including those with high risk features like POD24, primary refractory disease or high FLIPI scores. With almost a median of one year of follow-up, the one-year progression-free survival was 78% and the one-year duration of complete response was 89% suggesting that these responses are durable, at least so far. Responses seem to be durable for all patient subgroups, including those with POD24.
I think our data suggests that this combination leads to deep and so far quite durable responses with a manageable safety profile. Based on this encouraging data, there's an ongoing randomized Phase 3 trial comparing R2 to R2 plus epcoritamab among patients with relapsed or refractory follicular lymphoma. More broadly, I think this trial adds to a growing number of studies that suggest that CD3/CD20 bispecific antibodies are a very potent treatment for follicular lymphoma and will likely be an important part of our treatment for FL patients in the years to come.
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Isabelle L. Ray-Coquard, MD, PhD, of Centre Léon Bérard and the University Claude Bernard Lyon Est, discuss findings from the COLIBRI trial, which showed that, for patients with cervical squamous cell carcinoma, neoadjuvant nivolumab plus ipilimumab is safe and orchestrates de novo immune responses. The 82.5% complete response rate for primary tumors 6 months after standard chemoradiation therapy suggests favorable clinical outcomes (Abstract 5501).
Carmen E. Guerra, MD, MSCE, of the University of Pennsylvania Abramson Cancer Center, discusses three key abstracts presented at ASCO: strategies to increase accrual of underrepresented populations in Alliance NCTN trials, how patient-clinician education can strengthen partnerships and improve diversity in breast and lung cancer trials, and mediators of racial and ethnic inequities in clinical trial participation among U.S. patients with cancer from 2011 to 2022 (Abstracts 6509, 6510, 6511).
Enrique Grande, MD, of The University of Texas MD Anderson Cancer Center, discusses new findings that show initial responses to induction therapy with atezolizumab plus platinum and gemcitabine did not seem to impact overall survival for patients with metastatic urothelial carcinoma. Cisplatin-treated patients appeared to derive a greater benefit with atezolizumab than did carboplatin-treated patients (Abstract 4503).
Sarah K. Tasian, MD, of Children’s Hospital of Philadelphia, summarizes three studies presented at ASCO: genomic determinants of outcome in acute lymphoblastic leukemia (ALL), a phase III trial of inotuzumab ozogamicin for high-risk B-cell ALL, and preliminary results from the first-in-child phase II trial of bosutinib in pediatric patients with newly diagnosed chronic myeloid leukemia (Abstracts 10015, 10016, and 10017).
Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Adnan Khattak, MBBS, FRACP, PhD, of Australia’s Hollywood Private Hospital & Edith Cowan University, discuss the use of the mRNA-4157 vaccine in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma, which prolonged distant metastasis–free survival compared with pembrolizumab alone. These results provide further evidence that a personalized neoantigen approach is potentially beneficial (Abstract LBA9503).