View source for Epcoritamab-bysp

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|authorTag={{VSRN}}
|genericName=Epcoritamab
|aOrAn=a
|indicationType=treatment
|indication=Epcoritamab-bysp is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy.This indication is approved under accelerated approval based on response rate and durability of response.
|hasBlackBoxWarning=Yes
|adverseReactions=The most common (≥20%) adverse reactions are cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea.The most common Grade 3 to 4 laboratory abnormalities (≥10%) are decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
|blackBoxWarningTitle=Cytokine Release Syndrome And Immune Effector Cell-associated Neurotoxicity Syndrome
|blackBoxWarningBody=Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving EPKINLY. Initiate treatment with the EPKINLY step-up dosing schedule to reduce the incidence and severity of CRS. Withhold EPKINLY until CRS resolves or permanently discontinue based on severity.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including life-threatening and fatal reactions, can occur with EPKINLY. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold EPKINLY until ICANS resolves or permanently discontinue based on severity.
|fdaLIADAdult=Epcoritamab-bysp is available in the following dosage form(s) and strength(s):

Injection: 4 mg/0.8 mL in a single-dose vial. [ref] Dilute prior to use

Injection: 48 mg/0.8 mL in a single-dose vial; supplied as a ready-to-use solution that dose not need dilution prior to administration. 

Cycle and Day of Treatment
Dose of Epcoritamab-bysp
Cycle 1 day 1 (step-up dose 1)-   0.16 mg

Cycle 1 day 8 (step-up dose 2)-  0.8

Cycle 1 day 15 (first full dose)-    48 mg

Cycle 1 day 22-                              48 mg

Cycles 2 and 3 days 1, 8, 15, and 22-    48 mg

Cycles 4 to 9 days 1 and 15-                 48 mg

Cycle 10 and beyond day 1-                   48 mg
|contraindications=None
|warnings=Cytokine Release Syndrome

Epcoritamab can cause cytokine release syndrome (CRS), including serious or life-threatening reactions. 

Cytokine release syndrome occurred in 51% of patients receiving epcoritamab-bysp at the recommended dose in the clinical trial, with Grade 1 CRS occurring in 37%, Grade 2 in 17%, and Grade 3 in 2.5% of patients. Recurrent CRS occurred in 16% of patients. Of all the CRS events, most (92%) occurred during Cycle 1. In Cycle 1, 9% of CRS events occurred after the 0.16 mg dose on Cycle 1 Day 1, 16% after the 0.8 mg dose on Cycle 1 Day 8, 61% after the 48 mg dose on Cycle 1 Day 15, and 6% after the 48 mg dose on Cycle 1 Day 22. 

The median time to onset of CRS from the most recent administered epcoritamab-bysp dose across all doses was 24 hours (range: 0 to 10 days). The median time to onset after the first full 48 mg dose was 21 hours (range: 0 to 7 days).  CRS resolved in 98% of patients and the median duration of CRS events was 2 days (range: 1 to 27 days). 

In patients who experienced CRS, the signs and symptoms included pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia. 

Initiate therapy according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS following epcoritamab accordingly. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate.  Withhold or discontinue epcoritamab based on the severity of CRS. 

Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution. 

Immune Effector Cell-associated Neurotoxicity Syndrome

Epcoritamab can cause life-threatening and fatal immune effector cell-associated neurotoxicity syndrome (ICANS). 

ICANS occurred in 6% (10/157) of patients receiving epcoritamab-bysp at the recommended dose in the clinical trial, with Grade 1 ICANS in 4.5% and Grade 2 ICANS in 1.3% of patients. There was one (0.6%) fatal ICANS occurrence. Of the 10 ICANS events, 9 occurred within Cycle 1 of epcoritamab-bysp treatment, with a median time to onset of ICANS of 16.5 days (range: 8 to 141 days) from the start of treatment. Relative to the most recent administration of epcoritamab-bysp, the median time to onset of ICANS was 3 days (range: 1 to 13 days). The median duration of ICANS was 4 days (range: 0 to 8 days) with ICANS resolving in 90% of patients with supportive care.  Clinical manifestations of ICANS included, but were not limited to, confusional state, lethargy, tremor, dysgraphia, aphasia, and non-convulsive status epilepticus. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. 

Monitor patients for potential ICANS following epcoritamab. [ref] At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue epcoritamab per recommendations and consider further management per current practice guidelines.

Patients who experience signs or symptoms of ICANS or any other adverse reactions that impair cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution. 

Infections

Epcoritamab can cause serious and fatal infections.

In the clinical trial, serious infections, including opportunistic infections, were reported in 15% of patients treated with epcoritamab-bysp at the recommended dose with Grade 3 or 4 infections in 14% and fatal infections in 1.3%.  The most common Grade 3 or greater infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.

Monitor patients for signs and symptoms of infection prior to and during treatment with epcoritamab-bysp and treat appropriately. [ref] Avoid administration of epcoritamab in patients with active infections.  Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis prior to initiating treatment with epcoritamab; consider initiating prophylaxis against herpes virus prior to starting the drug. 

Withhold or consider permanent discontinuation of epcoritamab based on severity. 

Cytopenias

Epcoritamab can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. 

Among patients who received the recommended dosage of epcoritamab-bysp in the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 32%, decreased hemoglobin in 12%, and decreased platelets in 12% of patients. [ref] Febrile neutropenia occurred in 2.5%. 

Monitor complete blood counts throughout treatment. [ref] Based on the severity of cytopenias, temporarily withhold or permanently discontinue epcoritamab. Consider prophylactic granulocyte colony-stimulating factor administration as applicable. 

Embryo-fetal Toxicity

Based on its mechanism of action, epcoritamab may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. [ref] Advise females of reproductive potential to use effective contraception during treatment with epcoritamab and for 4 months after the last dose.
|clinicalTrials=The most common (≥20%) adverse reactions are cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea.  The most common Grade 3 to 4 laboratory abnormalities (≥10%) are decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets
|drugInteractions=It isessential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

For certain cytochrome P-450 (CYP) substrates, minimal changes in the concentration may lead to serious adverse reactions. [ref] Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with epcoritamab-bysp. 

Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of epcoritamab-bysp on Cycle 1 Day 1 and up to 14 days after the first 48 mg dose on Cycle 1 Day 15, and during and after CRS.
|administration=Injection, for subcutaneous use
|clinicalStudies=The efficacy of EPKINLY was evaluated in EPCORE NHL-1 (Study GCT3013-01; NCT03625037), an open-label, multi-cohort, multicenter, single-arm trial in 157 patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. The study excluded patients with CNS involvement of lymphoma, allogeneic HSCT or solid organ transplant, ongoing active infection, and any patients with known impaired T-cell immunity. Patients received EPKINLY monotherapy as a subcutaneous injection according to the following 28-day cycle schedule:

Cycle 1: EPKINLY 0.16 mg on Day 1, 0.8 mg on Day 8, 48 mg on Days 15 and 22
Cycles 2-3: EPKINLY 48 mg on Days 1, 8, 15, and 22
Cycles 4-9: EPKINLY 48 mg on Days 1 and 15
Cycles 10 and beyond: EPKINLY 48 mg on Day 1
Patients continued to receive EPKINLY until disease progression or unacceptable toxicity. In the setting of a suspected tumor flare reaction, continued treatment was permitted.

The efficacy population includes 148 patients with DLBCL, not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma. Of the 148 patients, the median age was 65 years (range: 22 to 83), 62% were male, 97% had an ECOG performance status of 0 or 1, and 3% had an ECOG performance status of 2. Race was reported in 125 (84%) patients; of these patients, 61% were White, 20% were Asian, and 0.7% were Native Hawaiian or Other Pacific Islander. There were no Black or African American or Hispanic or Latino patients treated in the clinical trial as reported. The diagnosis was DLBCL NOS in 86%, including 27% with DLBCL transformed from indolent lymphoma, and high-grade B-cell lymphoma in 14%. The median number of prior therapies was 3 (range: 2 to 11), with 30% receiving 2 prior therapies, 30% receiving 3 prior therapies, and 40% receiving 4 or more prior therapies. Eighteen percent had prior autologous HSCT, and 39% had prior chimeric antigen receptor (CAR) T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29% of patients were refractory to CAR T-cell therapy.
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