Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial

Thiéblemont, Catherine; Phillips, Tycel; Ghesquières, Hervé; Cheah, Chan Yoon; Clausen, Michael Roost; Cunningham, David; Rok, Young; Feldman, Tatyana; Gasiorowski, Robin; Jurczak, Wojciech; Kim, Tae Min; Lewis, David; Poel, Marjolein van der; Poon, Michelle; Stirner, Mariana Cota; Kilavuz, Nurgul; Chiu, Christopher; Chen, Menghui; Sacchi, Mariana; Elliott, Brian; Ahmadi, Tahamtan; Hutchings, Martin; Lugtenburg, Pieternella J.

doi:10.1200/jco.22.01725

Cited by 251 publications

(140 citation statements)

References 27 publications

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“…In phase 2 expansion cohorts of DLBCL patients, both glofitamab and epcoritamab have demonstrated CR rates of 39%, and the vast majority are durable [101,125]. Combination regimens are currently under investigation (including in firstline treatment), and as the CD3/CD20 bispecifics are arguably the most active single agents ever tested in DLBCL, they are likely to change the DLBCL treatment landscape in the years to come.…”

Section: Diffuse Large B-cell Lymphomamentioning

confidence: 99%

Novel precision medicine approaches and treatment strategies in hematological malignancies

et al. 2023

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Genetic testing has been applied for decades in clinical routine diagnostics of hematological malignancies to improve disease (sub)classification, prognostication, patient management, and survival. In recent classifications of hematological malignancies, disease subtypes are defined by key recurrent genetic alterations detected by conventional methods (i.e., cytogenetics, fluorescence in situ hybridization, and targeted sequencing). Hematological malignancies were also one of the first disease areas in which targeted therapies were introduced, the prime example being BCR::ABL1 inhibitors, followed by an increasing number of targeted inhibitors hitting the Achilles’ heel of each disease, resulting in a clear patient benefit. Owing to the technical advances in high‐throughput sequencing, we can now apply broad genomic tests, including comprehensive gene panels or whole‐genome and whole‐transcriptome sequencing, to identify clinically important diagnostic, prognostic, and predictive markers. In this review, we give examples of how precision diagnostics has been implemented to guide treatment selection and improve survival in myeloid (myelodysplastic syndromes and acute myeloid leukemia) and lymphoid malignancies (acute lymphoblastic leukemia, diffuse large B‐cell lymphoma, and chronic lymphocytic leukemia). We discuss the relevance and potential of monitoring measurable residual disease using ultra‐sensitive techniques to assess therapy response and detect early relapses. Finally, we bring up the promising avenue of functional precision medicine, combining ex vivo drug screening with various omics technologies, to provide novel treatment options for patients with advanced disease. Although we are only in the beginning of the field of precision hematology, we foresee rapid development with new types of diagnostics and treatment strategies becoming available to the benefit of our patients.

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Section: Diffuse Large B-cell Lymphomamentioning

confidence: 99%

Novel precision medicine approaches and treatment strategies in hematological malignancies

et al. 2023

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“…Many bsAbs are in development and expected to be approved in the near future. Glofitamab and epcoritamab, both CD20/CD3 bsAbs, were shown to be effective for heavily pretreated large B cell lymphomas [ 153 , 154 ], and talquetamab, directed against GPRC5D in myeloma, has demonstrated efficacy in relapsed multiple myeloma [ 155 ]. There are also six CAR T therapies currently approved for clinical use, including four anti-CD19 CAR T (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) therapies to treat B cell malignancies, and two anti-BCMA CAR T (idecabtagene vicleucel and ciltacabtagene autoleucel) therapies for relapsed/refractory multiple myeloma, as well as many others being tested against new targets and in other cancers.…”

Section: Special Populations and Treatment-related Hlhmentioning

confidence: 99%

Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis

Lee

Logan

2023

Cancers

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Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe, dysregulated inflammation driven by the inability of T cells to clear an antigenic target. When associated with malignancy (mHLH), the HLH syndrome is typically associated with extremely poor survival. Here, we review the diagnosis of secondary HLH (sHLH) syndromes in adults, with emphasis on the appropriate workup and treatment of mHLH. At present, the management of HLH in adults, including most forms of mHLH, is based on the use of corticosteroids and etoposide following the HLH-94 regimen. In some cases, this therapeutic approach may be cohesively incorporated into malignancy-directed therapy, while in other cases, the decision about whether to treat HLH prior to initiating other therapies may be more complicated. Recent studies exploring the efficacy of other agents in HLH, in particular ruxolitinib, offer hope for better outcomes in the management of mHLH. Considerations for the management of lymphoma-associated mHLH, as well as other forms of mHLH and immunotherapy treatment-related HLH, are discussed.

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“…For patients not candidates for CAR T cell therapy or those who progress afterward, outcomes have been exceedingly poor, however, bispecific antibodies have emerged as a very efficacious option in this setting with a manageable safety profile. To date, two products have been approved for use, epcoritamab has been granted accelerated approval by the FDA based on results from a single arm phase 1/2 study [7 ▪▪ ], while glofitamab has been approved in Canada based on a single arm phase 2 study [8 ▪ ].…”

Section: Large B Cell Lymphomamentioning

confidence: 99%

Update on bi-specific monoclonal antibodies for blood cancers

Shouse

2023

Current Opinion in Oncology

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Purpose of review The purpose of this review is to present updates in the field of bispecific antibodies focusing on those agents that have been recently approved for multiple myeloma, follicular lymphoma and diffuse large B cell lymphoma. Recent findings Teclistamab, the β-cell maturation antigen -targeted bispecific antibody has shown efficacy and tolerability in the fourth line setting for multiple myeloma. Mosunetuzumab, the CD20-targeted bispecific antibody has shown excellent response rates and durability in third line and beyond follicular lymphoma. Epcoritamab and glofitamab have both shown excellent response rates in heavily pretreated patients with diffuse large B cell lymphoma including those with prior chimeric antigen receptor T cell therapy. The toxicity is significant but manageable for both agents. Epcoritamab is approved by the FDA in the United States, while glofitamab is approved for use in Canada for patients with diffuse large B cell lymphoma refractory to 2 or more prior lines of therapy. Summary Bispecific antibodies represent a novel therapeutic resource that is poised to dramatically change the treatment landscape of many hematologic malignancies, but so far, initial successes include multiple myeloma, follicular lymphoma, and diffuse large B cell lymphoma, where several agents have been recently approved.

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Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial

Cited by 251 publications

References 27 publications

Novel precision medicine approaches and treatment strategies in hematological malignancies

Novel precision medicine approaches and treatment strategies in hematological malignancies

Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis

Update on bi-specific monoclonal antibodies for blood cancers

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