Regimen may become new standard for relapsed/refractory diffuse large B-cell lymphoma
Key takeaways:
- Combining epcoritamab-bysp with standard chemotherapy significantly improved response for patients with relapsed/refractory DLBCL.
- The regimen also significantly extended survival.
The addition of epcoritamab-bysp to standard chemotherapy significantly improved response and survival for patients with relapsed or refractory diffuse large B-cell lymphoma, according to results of a phase 1b/phase 2 trial.
More than 80% of participants achieved a response, and combining epcoritamab-bysb (Epkinly; Genmab, AbbVie) — a CD3xCD20 bispecific antibody — with gemcitabine plus oxaliplatin (Gem-Ox) nearly doubled survival compared with data on other salvage therapies.
“We expected the clinical outcomes to be good but were surprised about how good they were,” Joshua D. Brody, MD, director of the lymphoma immunotherapy program at The Tisch Cancer Institute at Mount Sinai, told Healio. “CD20xCD3 bispecific antibodies plus Gem-Ox will likely become a new standard of care for patients with relapsed/refractory DLCBL.”
Background
DLBCL accounts for about 30% of all non-Hodgkin lymphoma diagnoses, according to study background.
Patients with relapsed or refractory disease who cannot receive high-dose therapy or autologous stem cell transplantation typically have poor outcomes.
Individuals who do not undergo transplant often receive an immunochemotherapy regimen of Gem-Ox and rituximab (Rituxan; Genentech, Biogen). The combination produces a 33% complete response rate, median PFS of 5 months and median OS of 10 months. One published study showed median PFS of 3.6 months and median OS of 12.9 months.
Epcoritamab-bysp has been approved for adults with relapsed or refractory DLBCL or follicular lymphoma who have had at least two lines of prior therapy.
In the EPCORE NHL-1 phase 2 trial, patients with third-line-or-later large B-cell lymphoma had an ORR of 59% and complete response rate of 41% after follow-up of more than 2.5 years.
Of patients who had a complete remission, 62% stayed in remission at 2 years.
“Immunotherapy with CD20xCD3 bispecific antibodies yields complete remissions in more than a third of patients with relapsed DLBCL and is sufficiently well tolerated that it might be safe to combine with chemotherapy,” Brody said.
Methods
The EPCORE NHL-2 phase 1b/2 trial evaluated epcoritamab-bysp in combination with Gem-Ox for adults with relapsed or refractory CD20 DLBCL who could not receive transplantation.
The trial included 103 participants (median age, 72 years; range, 20-87; 55.3% men; 75.7% white).
They received subcutaneous epcoritamab-bysp as part of 28-day cycles until disease progression or unacceptable toxicity.
Participants received epcoritamab-bysp once weekly for cycles one to three, once every 2 weeks for cycles four to nine, and once weekly for subsequent cycles.
In cycle 1, they received 0.16 mg epcoritamab-bysp on day 1, 0.8 mg on day 8 and full doses on days 15 and beyond.
During the dose-escalation portion of the study, participants received either 24 mg or 48 mg as a full dose. Everyone in the expansion part of the trial received 48 mg.
Patients also received 1,000 mg/m² intravenous gemcitabine and 100 mg/m² oxaliplatin every 2 weeks for the first four cycles.
ORR served as the primary endpoint. Complete response rate, time to response, duration of response and complete response, OS and PFS served as secondary endpoints.
Results and next steps
At median follow-up of 13.2 months (range, 1-34.6), an independent review committee calculated an 85% ORR and a 61% complete response rate.
The overall study population had a median PFS of 11.2 months (95% CI, 8-14.7) and median OS of 21.6 months.
Those who had a complete response had a median PFS of 26.7 months (95% CI, 11.7 to not reached) and did not reach a median OS.
Results showed median time to response of 1.5 months, median time to complete response of 2.6 months, median duration of response of 11.7 months and median duration of complete response of 23.6 months (95% CI, 11.7 to not reached).
Roughly 60% of participants who achieved complete response remained in response at 12 months.
At data cutoff, 43% of patients continued to receive treatment. Of those who discontinued, 31% stopped due to progressive disease and 19% stopped because of adverse events.
The most common treatment-emergent adverse events (TEAEs) included thrombocytopenia (73%), infections (72%), neutropenia (65%), anemia (59%) and cytokine release syndrome (52%).
The most common grade 3 or worse TEAEs included thrombocytopenia (59%), neutropenia (57%) and anemia (43%).
In all, 13% of patients suffered a grade 5 TEAE. COVID-19 accounted for more than one-third (38.4%) of grade 5 TEAEs.
Researchers acknowledged study limitations, including lack of a control group and limited diversity of the cohort.
“[It is] likely CD20xCD3 bispecific antibodies can be combined safely with most chemotherapies, including front-line [rituximab, doxorubicin, cyclophosphamide, vincristine and prednisolone (R-CHOP)], and this is being tested now in ongoing trials,” Brody said.
For more information:
Joshua D. Brody, MD, can be reached at joshua.brody@mssm.edu.
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