NCCN Guidelines Support Epcoritamab Use in Diffuse Large B-Cell Lymphoma

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Epcoritamab is a treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma that was approved by the FDA based on findings from the phase 1/2 EPCORE NHL-1 trial.

The FDA previously approved epcoritamab for relapsed/refractory DLBCL based on findings from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).

The FDA previously approved epcoritamab for relapsed/refractory DLBCL based on findings from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).

Treatment with epcoritamab-bysp (Epkinly) is now recommended in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as an option in third- and subsequent lines of treatment for patients with diffuse large B-cell lymphoma (DLBCL), according to the updated B-cell lymphoma guidelines.1

Epcoritamab was designed as a subcutaneously administered IgG1-bispecific antibody that uses a DuoBody® technology, which directs cytotoxic T cells to produce an immune response towards target cell types. The agent binds to T cells expressing CD3 and B cells expressing CD20 to attack CD20-positive cells.

“The NCCN Guidelines are a resource for treating various types of cancer and providing health care providers with information for making informed treatment decisions,” Judith Klimovsky, MD, executive vice president and chief development officer at Genmab, said in a press release on the guidelines update.2 “We are pleased that the NCCN has updated its Guidelines to include epcoritamab in a speedy manner.

According to the press release, the boxed warnings for epcoritamab note cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as potential adverse effects (AEs) associated with treatment.3 Manufacturers advise beginning treatment in accordance with a step-up dosing schedule to minimize the risk and severity of CRS and to withhold or permanently discontinue the agent if CRS events persist. Additionally, it is recommended to observe patients for neurological signs of ICANS and to withhold or discontinue treatment depending on symptom severity.

In terms of other safety information, treatment with epcoritamab may cause severe cytopenias including neutropenia, anemia, and thrombocytopenia. It is recommended to surveil complete blood counts throughout treatment and potentially consider administering prophylactic granulocyte colony-stimulating factor. Moreover, due to the possibility of embryo-fatal toxicity, patients of reproductive potential are recommended to use effective contraception while receiving epcoritamab, including for 4 months after the final dose.

The authors of the NCCN Guidelines have recommended epcoritamab as an appropriate treatment for DLBCL alongside other therapy options depending on various clinical factors.

Third-Line and Subsequent-Lines in DLBCL

The updated guidelines highlight that epcoritamab is a suitable treatment for DLBCL in the third line, as well as in subsequent lines of treatment. This indication also includes the agent as a suitable treatment for those in the aforementioned lines who experienced disease progression following transplantation or CAR T-cell therapy.

According to the guidelines, other T-cell–mediated therapies that are currently appropriate options in the third and subsequent lines include anti-CD19 CAR T-cell agents axicabtagene ciloleucel (Yescarta), lisocabtagene maraleucel (Breyanzi), and tisagenlecleucel (Kymriah). Moreover, non-T-cell–mediated therapy options that are recommended in these settings include loncastuximab tesirine-lpyl (Zynlonta) and selinexor (Xpovio), including for those with disease progression following CAR T-cell therapy or transplantation.

Role of Epcoritamab in Histologically Transformed DLBCL

The guidelines authors also issued a category 2A recommendation for epcoritamab in indolent lymphomas that have histologically transformed into DLBCL.

If there is no intention for a patient to undergo transplantation following histologic transformation and receipt of an anthracycline-based regimen, epcoritamab is considered to be the preferred treatment after a minimum of 2 lines of systemic therapy. This indication includes those who experienced disease progression after prior transplantation or CAR T-cell therapy.

Other preferred regimens for this indication include polatuzumab vedotin-piiq (Polivy) with or without bendamustine (Treanda) and rituximab (Rituxan), and tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) if a patient has previously received an anthracycline-based combination. If not previously administered, cyclophosphamide plus doxorubicin, prednisone, rituximab, and vincristine (R-CHOP) is also a recommended option in this setting.

If there is no intent for a patient to continue with transplantation, other recommended treatments include cyclophosphamide plus etoposide, vincristine, and prednisone with or without rituximab (CEOP); loncastuximab tesirine; and selinexor in the case of transformed follicular lymphoma only following at least 2 previous lines of therapy.

The recommendations for epcoritamab in the previously described contexts are based on the FDA approval of epcoritamab for relapsed/refractory DLBCL, high-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6, high-grade B-cell lymphoma not otherwise stated, and DLBCL arising from follicular lymphoma and marginal zone lymphoma.4

Epcoritamab FDA Approval and the Phase 1/2 EPCORE NHL-1 Trial

Supporting data for the FDA approval of epcoritamab and the NCCN’s subsequent recommendations in the updated guidelines came from the phase 1/2 EPCORE NHL-1 trial (NCT03625037), in which investigators evaluated the agent among patients with relapsed/refractory CD20-positive mature B-cell non-Hodgkin lymphoma including those with DLBCL.5

Epcoritamab produced an overall response rate of 61% (95% CI, 53%-69%). Investigators also reported a complete response rate of 38%. With a median follow-up of 9.8 months, the estimated median duration of response was 15.6 months (95% CI, 9.7-not reached).

Frequent any-grade treatment-emergent AEs (TEAEs) consisted of CRS (49.7%), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), diarrhea (20.4%), and injection site reactions (19.7%). Investigators also reported several high-grade toxicities such as neutropenia (14.6%), anemia (10.2%), and neutrophil count decreases (6.4%).

References

  1. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 4.2023. Accessed June 28, 2023. https://bit.ly/44VJO83
  2. Genmab announces epcoritamab added to National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for ‘B-cell lymphomas.’ News release. Genmab. June 22, 2023. Accessed June 28, 2023. https://shorturl.at/dfmBD
  3. EPKINLY (epcoritamab-bysp) injection, for subcutaneous use. Prescribing information. Genmab. 2023. https://shorturl.at/ejDHM
  4. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. News release. FDA. May 19, 2023. Accessed June 28, 2023. bit.ly/45j0zeg
  5. Genmab announces late-breaking phase 2 trial results of investigational epcoritamab (DuoBody®-CD3xCD20) in relapsed/refractory large B-cell lymphoma (LBCL) presented at European Hematology Association (EHA) Presidential Symposium. News release. Genmab. June 11, 2022. Accessed July 11, 2023. http://bit.ly/3EPMREh
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