Review on Epcoritamab: A New FDA-Approved Medicine for Adult Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma

Ansari Owais Ahmad*, Pradeep Kumar Mohanty, Pradeep Kumar Yadav

SOP, LNCT University, J.K. Town, Kolar Road, Bhopal, Madhya Pradesh 462042.

*Correspondence: owais9235@gmail.com; Tel.: (8624817498)

INTRODUCTION

An illness known as cancer develops when some body cells proliferate out of control and infect other parts of the body. With billions of cells making up the human body, cancer may begin practically anywhere. Human cells normally divide and develop to create new cells as the body requires them. New cells replace old ones when they die as a result of aging or injury. Sometimes this carefully regulated system breaks down, allowing damaged or abnormal cells to multiply and spread when they shouldn't. These cells have the ability to create masses of tissue called tumors. [1]

Cellular DNA alterations, or mutations, are the root cause of cancer. The DNA of a cell is arranged into several unique genes, each of which contains a set of instructions governing the development and division of the cell as well as the functions it should do. [2]

Depending on what kind of cancer it is, there are several treatment options. Treatment options for cancer include surgery, chemotherapy, radiation treatment, immunotherapy, targeted therapy, bone marrow or stem cell transplantation, and hormone therapy. [3]

Diffuse large B-cell lymphoma (DLBCL):

Diffuse large B-cell lymphoma (DLBCL) is a malignancy that affects B cells, which are lymphocytes that are involved in antibody production. Mutations in B cells result in diffuse large B-cell lymphoma. The most prevalent non-Hodgkin lymphoma globally is diffuse large B cell lymphoma (DLBCL), accounting for 30–40% of cases across various geographical locations. About 60–70% of patients with diffuse large B-cell lymphoma survive for five years. The course of treatment for B cell lymphomas is contingent upon the molecular subtype, illness kind (aggressive or indolent), and staging. [4][5]

The FDA has authorized Epkinly (epcoritamab-bysp) injection for the management of adult patients with high-grade B cell lymphoma following two or more lines of systemic therapy, as well as patients with diffuse large B-cell lymphoma (DLBCL) that has relapsed or is refractory, unless otherwise noted. This includes DLBCL resulting from indolent lymphoma.

Epcoritamab:

A monoclonal antibody anticancer drug called epcoritamab is used to treat diffuse large B-cell lymphoma. Epcoritamab-bysp received accelerated approval from the Food and Drug Administration on May 19, 2023, for the treatment of diffuse large B-cell lymphoma (DLBCL) that has relapsed or is refractory, including DLBCL resulting from indolent lymphoma and high-grade B-cell lymphoma following two or more lines of systemic therapy.

In 148 patients with relapsed or refractory B-cell lymphoma following two or more lines of systemic treatment, including at least one anti-CD20 monoclonal antibody-containing therapy, epcoritamab was assessed in the EPCORE NHL-1 (NCT03625037) study. [6]

The overall response rate (ORR), which stood at 61%, was the effectiveness outcome measure. 38% of those patients were able to respond completely.

EPCORE NHL-1 (NCT03625037) was an open-label, multi-cohort, multicenter, single-arm experiment that assessed epcoritamab-bysp, a bispecific CD20-directed CD3 T-cell engager, in patients with recurrent or refractory B-cell lymphoma. The efficacy population comprised 148 patients with high-grade B-cell lymphoma following two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy, and relapsed or refractory DLBCL, not otherwise specified, including DLBCL resulting from indolent lymphoma.

Epcoritamab is a bispecific IgG1 antibody that binds to CD20 on B-cells and CD3 on T-cells at the same time. Because it can bind to both CD20 and CD3, epcoritamab facilitates T-cell activation and expansion, which in turn triggers T-cell-mediated destruction of CD20+ malignant B cells. An aggressive form of cancer called diffuse large B-cell lymphoma (DLBCL) is often treated with many rounds of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients with recurrent or refractory DLBCL have dismal prognosis, despite the fact that this regimen is successful in up to 60% of patients. With few discontinuations, controllable side effects, sustained complete responses, and high response rates are all associated with Epcoritamab usage in this patient category.

Adults with relapsed or refractory diffuse large B-cell lymphoma, particularly those resulting from indolent lymphoma, and high-grade B-cell lymphoma following two or more lines of systemic therapy, should be treated with epcoritamab. Cytokine release syndrome, weariness, musculoskeletal discomfort, injection site responses, pyrexia, stomach pain, nausea, and diarrhea are among the most frequent side events.

Epcoritamab-bysp is administered subcutaneously (into the skin) by a physician or nurse in a hospital or other medical setting. The injection is commonly made into the lower abdomen or thigh. It is often administered on days 1, 8, 15, and 22 during cycles 1-3, on days 1 and 15 during cycles 4–9, and on day 1 every month after that. [7]

Clinical Pharmacology: [8] [9]

Mechanism of action:

A bispecific IgG1 antibody that has been humanized, epcoritamab binds to CD20 on B-cells and CD3 on T-cells. Epcoritamab can identify and bind two distinct targets, the CD3 receptor expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells and healthy B-lineage cells, in contrast to other monoclonal antibodies that target a single receptor on the surface of lymphocytes. Epcoritamab stimulates the production of proinflammatory cytokines and selective T-cell-mediated cytotoxic activity, which leads to the lysis of CD20+ malignant B-cells. This is achieved by targeting both receptors.

Pharmacodynamics

Epcoritamab usage may result in decreased B-cell circulating numbers. Circulating B-cells fell to undetectable levels and remained diminished for the duration of therapy when individuals with detectable B-cell levels received the prescribed amount of epcoritamab following the first complete dose of 48 mg. At dosages equivalent to or more than 0.04 mg, epcoritamab may also temporarily increase circulating cytokines such as TNF-α, IFN-γ, IL-6, IL-10, and IL-2. Cytokine levels rose 24 hours after the first dosage of epcoritamab on cycle 1 day 1 and peaked after the first 48 mg dose on cycle 1 day 15. On cycle 1 day 22, cytokine levels stabilized prior to the administration of the subsequent 48 mg full dosage.

Epcoritamab usage has been linked to immunological effector cell-associated neurotoxicity syndrome, which can be lethal as well as cytokine release syndrome. Moreover, infections, cytopenias, and embryo-fetal damage might result from it.

Pharmacokinetics

Unless otherwise noted, pharmacokinetic (PK) parameters are given as geometric mean (CV%) and were assessed at the authorized recommended dose of 48 mg. AUC (area under the concentration-time curve) for epcoritamab-bysp rose across the whole dose range of 1.5 to 60 mg, or 0.03125 to 1.25 times the suggested recommended dosage, more than proportionately.  The maximal concentration of epcoritamab-bysp (11.1 mcg/mL [41.5%]) is reached following the Q2W regimen's first dose, or the 11th dose of 48 mg during Cycle 4's first dosage.

Absorption

After the first complete dosage and the completion of the weekly dosing regimen (end of Cycle 3) treatment doses, the median (range) Tmax of epcoritamab-bysp was 4 (0.3 to 7) days and 2.3 (0.3 to 3.2) days, respectively.

Distribution

25.6 L (82%), is the apparent total volume of distribution.

Metabolism
Catabolic processes are anticipated to metabolize epcoritamab-bysp into tiny peptides.

Elimination

At the conclusion of Cycle 3, the half-life of the whole dosage of epcoritamab-bysp (48 mg) was about 22 days (58%) and the apparent total clearance was approximately 0.53 L/day (40%).

Specific Populations

Age (20 to 89 years), sex, race (White or Asian), and mild to severe renal impairment (calculated using the Cockcroft-Gault method, with a creatinine clearance [CLcr] of 30 to less than 90 mL/min), and mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN and any AST) did not show any clinically significant differences in the PK of epcoritamab-bysp after bodyweight adjustments were taken into consideration. We do not know how the PK of epcoritamab bysp is affected by severe renal impairment (CLcr 15 to < 30 mL/min), end-stage renal disease (CLcr < 15 mL/min), or moderate to severe hepatic impairment (total bilirubin > 1.5 times ULN and any AST).

Body Weight

When compared to patients with a body weight (BW) of 65 to less than 85 kg, patients who received the indicated dosage of EPKINLY had a Cycle 1 median average concentration that was 13% lower in the higher BW group (85 to 144 kg) and 37% higher in the lower BW group (39 to 65 kg).

Preclinical studies: [10] [11]

Methods:

To assess the effect on T cells and target cells, pre-treatment with SOC components (LEN, CPA, DOX, VINC, or PRD) was given to healthy donor T cells (effector cells) and/or B-NHL tumor cell lines expressing CD20. The same SOC was incubated with pre-treated T and B-NHL cells in the presence of epcoritamab. Flow cytometry was used to measure the related T-cell activation and T-cell mediated cytotoxicity. In order to evaluate potential antagonistic effects, bendamustine or GEMOX was administered together with epcoritamab during the T-cell activation and cytotoxicity experiment.

Results

Epcoritamab demonstrated strong and specific T-cell-mediated cytotoxic activity against malignant B cells that were CD20-positive (CD20+) in preclinical trials. Differentiating epcoritamab from traditional CD20 monoclonal antibodies (mAbs) that cause T-cell cytotoxicity through Fc-mediated effector functions, the formation of the epcoritamab/CD20/CD3 trimer results in the activation and expansion of T cells as well as T-cell-mediated killing of CD20+ malignant B cells. Epcoritamab had notably greater efficacy at lower doses in vitro when compared to three other CD3xCD20 bsAb analog constructions; effective concentrations at half maximum cytotoxic activity against B-cell lymphoma cell lines and endogenous B cells varied from 0•2 to 3•5 pM. This resulted in the notable observation that epcoritamab maintained its anti-tumor action in vivo when an analog of rituximab was present. An in vivo investigation in cynomolgus monkeys supports the subcutaneous (SC) administration of epcoritamab by showing a comparable degree of sustained B-cell depletion with SC and intravenous (IV) treatment. Crucially, SC administration also produced cytokine levels that peaked later and at a lower level, indicating that using the SC route of delivery may lessen the chance of developing severe CRS. Both newly diagnosed patients and malignant B cells extracted from B-NHL patients who had previously received CD20 antibody treatment showed cytotoxic activity in response to epcoritamab.

Overall, these results prompted the start of a phase 1/2 dose-escalation and expansion trial of SC epcoritamab in patients with R/R B-NHL, which is now a first-in-human (FIH) study (NCT03625037). We provide results from the phase 1 dose-escalation portion of this ongoing investigation, where the main goals were to ascertain the phase 2 dosage recommendation (RP2D) and the maximum tolerated dose (MTD).

Phase 1 and 2 Trial:

Study Design and Patients:

Phase I/II, single-arm, multicenter, open-label, dose-escalation/expansion trial (EPCORE NHL-1; GCT3013-01; ClinicalTrials.gov identifier: NCT03625037) for patients with refractory, progressing, or relapsed mature B-cell lymphoma.

Patients met the eligibility requirements if they had a documented CD201 mature B-cell neoplasm (diffuse large B-cell lymphoma [DLBCL] or other aggressive non-Hodgkin lymphoma, such as primary mediastinal LBCL, high-grade B-cell lymphoma, or follicular lymphoma grade 3B) and were at least 18 years old with a performance status of 0 to 2. Relapsed or resistant illness, treatment with a minimum of two previous lines of systemic therapy, including a minimum of one anti-CD20-containing regimen, and previous failure or ineligibility for autologous stem-cell transplantation were additional inclusion criteria. Refractory disease was defined as progression occurring either during therapy or within six months of therapy completion, whereas relapsed disease was defined as recurrence occurring at least six months after therapy ended. Patients qualified if there has been more than 30 days since their last CAR T-cell treatment. A minimum life expectancy or an absolute leukocyte count were not necessary. The Data Supplement provides complete inclusion and exclusion criteria (available only online).

Subcutaneous epcoritamab was administered to the patients using a cycle 1 step-up dosage schedule that included a 0.16-mg priming dose once on day 1, a 0.8-mg intermediate dose once on day 8, and full 48-mg doses once on day 15 and every day after that until the illness progressed or the level of toxicity was intolerable. Epcoritamab was injected weekly in cycles 1-3, every two weeks (days 1 and 15) in cycles 4–9, and every four weeks starting in cycle 10. There was no first-line B-cell-depleting medication used. Prednisolone 100 mg oral (or intravenous equivalent) was given 30-120 minutes prior to each epcoritamab dose (once daily on days 1-4 for the priming dose, once daily on days 8-11 for the intermediate dose, once daily on days 15-18 for the first full dose, and once daily on days 22-25 for the second full dose) as part of the prophylactic treatment for cytokine release syndrome (CRS) during cycle 1. Moreover, on days 1, 8, 15, and 22 of cycle 1, acetaminophen 650–1,000 mg orally and diphenhydramine 50 mg orally or intravenously (or equivalent) were given once daily. Corticosteroids were administered with epcoritamab for four days, or until the occurrence of resolution of CRS, if grade 2 or higher CRS was observed following the fourth dosage of epcoritamab during cycle 1.For the first complete dosage of epcoritamab, 24-hour inpatient monitoring was necessary to guarantee patient safety and to further diagnose CRS.
Before the study began, the Protocol (available only online) was authorized by institutional or central ethics committees, as well as review boards particular to the study location. The International Council for Harmonization's E6 (R2) recommendations on good clinical practice and the Declaration of Helsinki's tenets were followed in the conduct of the study. Before being enrolled, all patients read and signed informed consent papers. [12]

End Points and Assessments [13] [14] [15] [16]
The independent review committee's (IRC) overall response rate (ORR) utilizing the Lugano criteria was the main outcome. The following were secondary end points: OS, progression-free survival (PFS), time to response per IRC, duration of response (DOR), complete response (CR) rate, and length of CR. Analysis of subgroups was predetermined. Furthermore, circulating tumor DNA was used to measure minimum residual disease (MRD) using the clonoSEQ MRD test (Adaptive Biotechnologies, Seattle, WA; Data Supplement). Adverse occurrences (AEs) and test abnormalities were examples of safety end goals. The investigator determined whether an adverse event was related to the therapy.

The MRD evaluation, physical examination, and imaging evaluations (computed tomography, magnetic resonance imaging, and obligatory fluorodeoxyglucose positron emission tomography) were performed at weeks 6, 12, 18, 24, 36, and 48, and then every 24 weeks after that.

The National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, was used to rate the severity of AEs, while the Medical Dictionary for Regulatory Activities, or MedDRA, version 24.1, was used to code them. American Society for Transplantation and Cellular Therapy criteria were used to assess CRS and immunological effector cell-associated neurotoxicity syndrome (ICANS). Cairo-Bishop's criteria were used to assess cases of clinical tumor lysis syndrome. The Data Supplement provides an overview of other evaluations, such as pharmacokinetics, antidrug antibodies, and patient-reported outcomes.

Statistical Analysis [16]

There were two phases to the enrollment process; the first stage included the enrollment of 28 DLBCL patients. A preliminary study was carried out after a maximum of twelve weeks of follow-up for about twenty-five DLBCL patients. Since the futility ending criteria were not satisfied, a further 100 DLBCL patients were added in the second stage of the study, up to 30 of whom had severe non-Hodgkin lymphomas of different kinds. The percentage of patients who experienced a partial response (PR) or the best overall response (CR) was called the ORR. Before the start of the subsequent antilymphoma therapy, the best overall response according to the response criteria was compiled. IRC-assessed response according to Lugano criteria was the main method used to analyze ORR for the whole analytic population, which included all patients who had at least one dosage of epcoritamab. We computed the ORR and the matching 95% precise CI. PFS was defined as the amount of time from cycle 1 day 1 to the first recorded progression of the illness or, if it happened sooner, the date of death from any cause. Before the commencement of further antilymphoma therapy, patients who were still alive and had not seen any illness progression at the cutoff date were excluded at the time of the last evaluable disease evaluation. PFS was censored on day 1 of cycle 1 for patients who were still alive but had an incomplete or nonexistent baseline tumor evaluation. Kaplan-Meier estimates (median time and 95% CI) were used to examine time-to-event end points (DOR, PFS, and OS), and the number and percentage of patients who experienced an incident or censoring were reported. The whole analysis set (all patients who received at least one dosage of epcoritamab) was used for efficacy analyses, and the full analysis set was also used for safety studies. For PFS by MRD status, a groundbreaking analysis was carried out up to cycle 3 day 1 (day 60, taking into account 6 3-day window). SAS software version 9.4 (SAS Institute, Inc., Cary, NC; Data Supplement) was used to analyze the data.

Patients and Treatment Exposure [16]

Enrolled at 54 worldwide locations and treated with epcoritamab were 157 patients between June 19, 2020, and the data cutoff date of January 31, 2022. After 106 patients had a median follow-up of 10.7 months, the study was stopped for 83 (52.9%) reasons: disease progression, 11 (7.0%) AEs, decision to undergo allogeneic transplantation, patient withdrawal, four (2.5%), and one (0.6%) after achieving a PR for CAR T-cell therapy. Patients had a median of three previous lines of treatment (range: 2–11); 96 patients (61.1%) had primary refractory illness, and 119 patients (75.6%) had not responded to two or more lines of therapy in a row. The median interval from the first diagnosis was 19 months, or 1.6 years. Sixty-one patients (38.9%) who had previously undergone CAR T-cell therapy experienced progressive disease (PD) within six months of the treatment. Epcoritamab treatment was administered to the patients for a median of five cycles (15 doses) (range, 1-20). 51 patients (32.5%) were still taking study therapy as of the data cutoff date, and 56.1% of them were still receiving it during the follow-up period.

Phase 3 Clinical trials: [17]

This is a phase 3 worldwide, multi-center, open-label randomized study of epcoritamab, also known as GEN313. This randomised trial aims to assess the effectiveness of epcoritamab (GEN3013, DuoBody®-CD3xCD20) in patients with relapsed, refractory diffuse large B-cell lymphoma who have not responded to or are not qualified for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) in comparison with the investigator's recommended chemotherapy. During the trial's treatment phase, participants are not allowed to switch up their chemotherapy.

The medicine that will be tested in the trial is an antibody, epcoritamab, commonly known as EPKINLY™ and GEN3013. This study's primary goal is to assess effectiveness, as epcoritamab's safety and tolerance have previously been investigated in human research. In order to assess this, epcoritamab will be administered to half of the eligible subjects, while the other half will receive chemotherapy of the investigator's choosing. Epcoritamab will be examined in R/R DLBCL patients who did not respond to a prior autologous stem cell transplant (ASCT) or do not match the criteria for ASCT.

Effectiveness: [18] [19] [20] [21] [22]

Epkinly was assessed in patients with relapsed or refractory B-cell lymphoma participating in the open-label, multi-cohort, multicenter, single-arm EPCORE NHL-1 (NCT03625037) experiment. The efficacy population comprised 148 patients with high-grade B-cell lymphoma following two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy, and relapsed or refractory DLBCL, not otherwise specified, including DLBCL resulting from indolent lymphoma.

Overall response rate (ORR), as defined by Lugano 2014 criteria and evaluated by an Independent Review Committee, served as the primary efficacy outcome measure. A complete response was obtained by 38% of patients, yielding an ORR of 61% (95% CI: 53, 69). Based on respondents' median follow-up of 9.8 months, the projected median response length was 15.6 months (95% CI: 9.7, not reached).

The FDA may approve medications for severe disorders if there is an unmet medical need and a treatment is demonstrated to have an effect on a surrogate or intermediate endpoint that is reasonably expected to anticipate a therapeutic benefit to patients. Epkinly is approved under this method. A Phase 3 randomized study comparing Epkinly to standard of care chemo immunotherapy regimens in patients with relapsed or refractory DLBCL is in underway in an effort to establish the therapeutic efficacy of the drug. The main result of the study is overall survival.

Subcutaneous injections of EPKINLY monotherapy were administered to patients in accordance with the following 28-day cycle schedule:
Cycle 1: 48 mg on Days 15 and 22, 0.8 mg on Day 8, and 0.16 mg on Day 1.
Cycles 2-3: Days 1, 8, 15, and 22 of EPKINLY 48 mg
Cycles 4–9: On Days 1 and 15, EPKINLY 48 mg
Cycles 10 and up: Day 1 EPKINLY 48 mg

Figure 1: Results of Epcoritamab's effectiveness (per IRC; Lugano criteria) in patients with LBCL. For patients with LBCL,

Displays the best percentage change in the sum-of-product perpendicular diameters of the target lesions. Patients who have already had CAR T-cell treatment are indicated with asterisks.

Displays the DOR Kaplan-Meier curve. In the DLBCL population, the results were comparable (data not shown).

Displays the PFS Kaplan-Meier plot. Using the Mantel-Byar technique, an ad hoc PFS analysis revealed a hazard ratio (95% CI) of 0.11 (0.04 to 0.25) for patients with CR against nonresponders, and 0.47 (0.26 to 0.86) for patients with PR over nonresponders. After six weeks of therapy, thirty-six patients either had a worsening of their condition (n = 28) or passed away (n = 8). End of data period: January 31, 2022. CAR is for chimeric antigen receptor; CR stands for complete response; DOR stands for duration of response; IRC stands for independent review committee; LBCL is a large B-cell lymphoma; PD stands for progressing disease; PFS stands for progression-free survival; PR stands for partial response; and SD stands for stable disease.

Epcoritamab ADR: [23] [24] [25] [26]

Cytokine release syndrome, weariness, musculoskeletal discomfort, injection site responses, pyrexia, stomach pain, nausea, and diarrhea are the most frequent (≥20%) side effects. Reduced white blood cell count, reduced hemoglobin, decreased platelet count, decreased neutrophil count, and decreased lymphocyte count are the most frequent Grade 3 to 4 laboratory abnormalities (≥ 10%).

Cytokine Release Syndrome (CRS)

While receiving EPKINLY therapy, CRS is frequently seen and has the potential to be fatal. Fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, difficulty breathing, chills, a rapid heartbeat, anxiety, headache, disorientation, shaking (tremors), issues with balance and mobility, such as difficulty walking, are some of the signs and symptoms of CRS.

Low quantities of blood cells:

During EPKINLY therapy, low blood cell counts are frequent and can potentially be severe or life-threatening. The following low blood cell counts might be brought on by EPKINLY:

Neutropenia is the low count of white blood cells. Your risk of infection may rise if your white blood cell count is low.

Low levels of red blood cells (anemia). A low red blood cell count can lead to fatigue and dyspnea.

Thrombocytopenia, or low platelet levels. Anemia or bleeding issues may be brought on by low platelet levels.

NONCLINICAL TOXICOLOGY [23]

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Studies on the carcinogenicity or genotoxicity of epcoritamab-bysp have not been carried out.
To yet, no specific research has been done to assess how epcoritamab-bysp affects fertility.
CONCLUSION

It was concluded, the FDA has allowed endorsement for Epkinly (epcoritamab-bysp) infusion for the administration of grown-up patients with high-grade B cell lymphoma taking after two or more lines of systemic treatment, as well as patients with diffuse huge B-cell lymphoma (DLBCL) that has backslid or is hard-headed, unless something else famous. This incorporates DLBCL coming about from slothful lymphoma. Epcoritamab, a bispecific CD20-directed CD3 T-cell engager, appeared tall reaction rates and solid total reactions in patients with backslid or hard-headed DLBCL, with sensible unfavorable occasions.

Epcoritamab is a bispecific antibody that targets CD20 on B-cells and CD3 on T-cells, promoting the release of proinflammatory cytokines and the lysis of malignant B-cells. It can cause low levels of circulating B-cells, transient elevation of cytokines, and potential side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The pharmacokinetic parameters of epcoritamab show increased exposure with higher doses and a half-life of approximately 22 days. There are no clinically significant differences in pharmacokinetics based on age, sex, race, mild to moderate renal impairment, or mild hepatic impairment. Body weight may affect the concentration of epcoritamab.

Epkinly, a drug approved under the accelerated approval pathway, showed promising results in a trial for patients with relapsed or refractory B-cell lymphoma, with an overall response rate of 61% and a median duration of response of 15.6 months. A Phase 3 trial is currently underway to confirm its clinical benefit compared to standard of care chemo immunotherapy regimens

In conclusion, the main adverse reactions of Epcoritamab include cytokine release syndrome, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea; while the most common Grade 3 to 4 laboratory abnormalities are decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets. Additionally, Epcoritamab can cause cytokine release syndrome with symptoms like fever, dizziness, trouble breathing, and low blood cell counts which can lead to an increased risk of infection, tiredness, shortness of breath, bruising, or bleeding problems.

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18.  Research C for DE and. FDA approves treatment for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA [Internet]. 2023 Jun 8; Available from: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-and-high-grade-b-cell

19.  ESMO. FDA Grants Accelerated Approval to Epcoritamab-bysp for Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma [Internet]. www.esmo.org. [cited 2024 Feb 17]. Available from: https://www.esmo.org/oncology-news/fda-grants-accelerated-approval-to-epcoritamab-bysp-for-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-and-high-grade-b-cell-lymphoma

20.  AM TAPSP 5/22/2023 10:21:00 ALU 5/22/2023 11:17:07. FDA Grants Accelerated Approval to Epcoritamab-bysp for Relapsed or Refractory B-Cell Lymphoma - The ASCO Post [Internet]. ascopost.com. [cited 2024 Feb 17]. Available from: https://ascopost.com/news/may-2023/fda-grants-accelerated-approval-to-epcoritamab-bysp-for-relapsed-or-refractory-b-cell-lymphoma/

21.  DailyMed - EPKINLY- epcoritamab-bysp injection, solution EPKINLY- epcoritamab-bysp injection, solution, concentrate [Internet]. dailymed.nlm.nih.gov. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7836711-b677-412d-bf2d-0f7c8444103a

22.  These highlights do not include all the information needed to use EPKINLY safely and effectively. See full prescribing information for EPKINLY. EPKINLYTM (epcoritamab-bysp) injection, for subcutaneous use Initial U.S. Approval: 2023 [Internet]. dailymed.nlm.nih.gov. [cited 2024 Feb 16]. Available from: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d7836711-b677-412d-bf2d-0f7c8444103a

23.  These highlights do not include all the information needed to use EPKINLY safely and effectively. See full prescribing information for EPKINLY. EPKINLYTM (epcoritamab-bysp) injection, for subcutaneous use Initial U.S. Approval: 2023 [Internet]. dailymed.nlm.nih.gov. [cited 2024 Feb 16]. Available from: https://dailymed.nlm.nih.gov/dailymed/medguide.cfm?setid=d7836711-b677-412d-bf2d-0f7c8444103a#:~:text=Low%20blood%20cell%20counts%20are

24.  Genentech: Press Releases | Sunday, Dec 10, 2023 [Internet]. www.gene.com. [cited 2024 Feb 16]. Available from: https://www.gene.com/media/press-releases/15015/2023-12-10/new-data-for-genentechs-columvi-and-luns

25.  What is 3L+ Follicular Lymphoma | LUNSUMIOTM (mosunetuzumab-axgb) [Internet]. lunsumio. [cited 2024 Feb 16]. Available from: https://www.lunsumio.com/about/what-is-follicular-lymphoma.html

26.  EPKINLYTM (epcoritamab-bysp) Approved by U.S. Food and Drug Administration as the First and Only Bispecific Antibody to Treat Adults with Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL) - Genmab A/S [Internet]. Genmab A/S. 2023 [cited 2024 Feb 16]. Available from: https://ir.genmab.com/news-releases/news-release-details/epkinlytm-epcoritamab-bysp-approved-us-food-and-drug