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Bispecific Antibody Epcoritamab in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma


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In a phase I/II study reported in The Lancet, Hutchings et al found that the novel bispecific antibody epcoritamab produced high response rates in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Epcoritamab works by targeting CD3 and CD20 and inducing T-cell–mediated cytotoxic activity against CD20-positive malignant B cells.

Study Details

Sixty-eight patients from sites in Denmark, the Netherlands, the United Kingdom, and Spain were enrolled in the study between June 2018 and July 2020. Patients received escalating priming, intermediate, and full doses (range = 0.0128–60 mg) of subcutaneous epcoritamab, with full doses given in 28-day cycles. Treatment at full doses continued until disease progression or unacceptable toxicity.

Responses

No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The full dose of 48 mg was identified as the recommended phase II dose. Among the 68 patients, full doses were ≤ 24 mg in 53, 48 mg in 12, and 60 mg in 3, with median durations of exposure of 8.1 weeks, 11.8 weeks, and 40.1 weeks, respectively.

Among 22 evaluable patients with diffuse large B-cell lymphoma receiving full doses of 12 to 60 mg, an objective response was observed in 15 (68%, 95% confidence interval [CI] = 45%–86%), with complete response in 10 (45%). Response deepened over time, with conversion from partial response at week 6 to complete response in five patients. Among eight patients receiving 40 mg, a response was observed in seven (88%, 95% CI = 47%–100%), with complete response in three (38%). The estimated probability of maintaining remission for ≥ 6 months was 75%.

KEY POINTS

  • Objective response was observed in 68% of patients with diffuse large B-cell lymphoma and 90% of those with follicular lymphoma.
  • All episodes of cytokine-release syndrome were grade 1 or 2.

Among 10 evaluable patients with follicular lymphoma receiving doses of 0.76 to 48 mg, objective response was observed in nine (90%, 95% CI = 55%–100%), with complete response in five (50%). Response deepened over time in three patients, who exhibited conversion from partial to complete response. Among four evaluable patients with mantle cell lymphoma receiving 0.76 to 48 mg, objective response was observed in two (50%), with complete response in one (25%).   

A rapid, deep, and sustained depletion of circulating peripheral B cells was observed, with expansion of CD4-positive and CD8-positive T cells after 6 to 8 weeks of treatment. Moderate increases in interferon γ, interleukin 6, and tumor necrosis factor α were observed.

Toxicity

Among the 68 patients, the most common adverse events of any grade were pyrexia (69%; 91% grade 1–2), cytokine-release syndrome (59%; all grade 1–2), and injection site reactions (47%; 97% grade 1). Serious adverse events occurred in 68% of patients, most commonly pyrexia (28%) and pneumonia.

Neurologic symptoms possibly related to treatment were observed in four patients, including grade 3 hypersomnia in one and grade 3 confusion and depressed level of consciousness in one. All neurologic events rapidly resolved. No treatment-related discontinuations of treatment occurred, and no treatment-related deaths were reported.

The investigators concluded, “Single-agent subcutaneous epcoritamab for treatment of patients with relapsed or refractory B-cell non-Hodgkin lymphoma merits investigation in ongoing phase II and phase III studies.”

Martin Hutchings, MD, of the Department of Haematology, Rigshospitalet, Copenhagen, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Genmab and AbbVie. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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