This promotional website is for UK Healthcare Professionals involved in the management of haematological malignancies. Adverse event reporting information can be found below.
I
Tepkinly is licensed
for 3L+ DLBCL
Tepkinly as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B‑cell lymphoma (DLBCL) after two or more lines of systemic therapy.1
Tepkinly has a conditional marketing authorisation
- further data awaited.
You are advised to read the Prescribing Information and Summary of Product Characteristics, accessible via the links above, to evaluate patient suitability for Tepkinly.
Adverse event reporting information can be found at the bottom of this page.
Tepkinly is licensed for 3L+ DLBCL
Tepkinly as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B‑cell lymphoma (DLBCL) after two or more lines of systemic therapy.1
Tepkinly has a conditional marketing authorisation
- further data awaited.
You are advised to read the Prescribing Information and Summary of Product Characteristics, accessible via the links above, to evaluate patient suitability for Tepkinly.
Adverse event reporting information can be found at the bottom of this page.
Adverse reactions reported in patients in EPCORETM NHL-11
The safety of Tepkinly was evaluated in a non-randomised, single-arm study in 167 patients with relapsed or refractory LBCL after two or more lines of systemic therapy and included all the patients who enrolled to the 48mg dose and received at least one dose of Tepkinly. The median duration of exposure to Tepkinly was 3.7 months (range: 0 to 25). The following adverse reactions have been reported with Tepkinly during clinical studies and post marketing experience.1
For full safety information, please refer to the SmPC
Tepkinly has a generally manageable safety profile1
- 4.8% (n=8/167) of patients in EPCORETM NHL-1 trial discontinued subcutaneous Tepkinly due to adverse reactions. Discontinuations due to pneumonia occurred in 3.6% (n=6/167) of patients and CRS, ICANS or fatigue occurred in 0.6% (n=1/167) of patients each.
- Serious adverse reactions occurred in 43.7% (n=72/167) of patients.
- 2.4% (n=4/167) of patients experienced a fatal adverse reaction (ICANS in 0.6% (n=1/167) of patients and pneumonia in 1.8% (n=3/167) of patients).
Adverse reactions for Tepkinly from clinical studies are listed by MedDRA system organ class and are based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); and very rare (<1/10,000).
CRS events with Tepkinly1-3
CRS of any grade occurred in 51% (n=85/167) patients treated with Tepkinly1
Predictable: Most CRS events occurred in Cycle 1 and were associated with the first full dose of Tepkinly1
- Median time to onset of CRS from the most recently administered dose was 2 days (range 1-11 days).
- Median time to onset after first full dose was 20.2 hours (0.2-7 days)
CRS events by dosing period in the NHL-1 trial at 2-year follow-up (full cohort, N=157)3
Manageable: Treatment was discontinued in 0.6% (n=1/167) of patients due to CRS1
- Dose delays due to CRS occurred in 7.2% (n=12/167) of patients1
Resolvable: CRS resolved in 98% (n=83/85)1
- Median duration of CRS events was 2 days (range: 1-27 days)
- Hospitalisations due to CRS occurred in 28% (n=47/167) of patients
- Median time to resolution for hospitalised patients (range: <1-26 days)
No new ICANS, CRS, or clinical TLS events occurred during extended follow-up of the NHL-1 trial; median follow-up time 25.1 months (95% CI, 24.0-26.0).3
Patients should be monitored for signs and symptoms of CRS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS1
CRS was generally low grade1,2
Management of CRS while using Tepkinly1
In The NHL-1 trial, tocilizumab was used to manage CRS events in 16% (n=14/85) of patients and corticosteroids were used in 11% (n=9/85) of patients.
ICANS occurrence with Tepkinly1,4
ICANS, including fatal events, have occurred in patients receiving Tepkinly1
ICANs occurred in 6% (n=10/167) of patients in the NHL-1 trial1
Frequency of ICANS by grade in the NHL-1 trial
- The median time to first ICANS onset from the start of Tepkinly treatment was 16.5 days (range: 8-141 days)
- Dose delays due to ICANS occurred in 1.8% (n=3/167) of patients
- ICANS resolved in 90% (9/10) of patients with supportive care
- The median time to resolution of ICANS was 5 days (range: 1-9 days)
No new ICANS, CRS, or clinical TLS events occurred during extended follow-up of the NHL-1 trial; median follow-up time 25.1 months (95% CI, 24.0-26.0).3
Patients should be monitored for signs and symptoms of ICANS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of ICANS1
Epcoritamab has major influence on the ability to drive and use machines. Due to the potential for ICANS, patients receiving epcoritamab are at risk of altered level of consciousness. Patients should be advised to exercise caution (or avoid if symptomatic) while driving, cycling or using heavy or potentially dangerous machines.1
Management of ICANs while using Tepkinly1
Epcoritamab has major influence on the ability to drive and use machines. Due to the potential for ICANS, patients receiving epcoritamab are at risk of altered level of consciousness. Patients should be advised to exercise caution (or avoid if symptomatic) while driving, cycling or using heavy or potentially dangerous machines.1
Serious infections of any grade occurred in 25% (n=42/167) of patients treated with Tepkinly1
- Serious or fatal infections were observed in patients treated with epcoritamab in clinical studies
- The most frequent serious infections were COVID-19, COVID-19 pneumonia, pneumonia, sepsis, cellulitis, upper respiratory tract infection, bacteraemia, septic shock and progressive multifocal leukoencephalopathy†
Frequency of serious infections
Fatal serious infections occurred in 7 patients (4.2%)
- Median time to onset of first serious infection was 56 days (range: 4-631 days)
- Median duration of serious infection was 15 days (range 4-125 days)
- Dose delays due to serious infections occurred in 15% (n=25/167) of patients
- Treatment discontinuations due to serious infections occurred in 6% (n=10/167) of patients
- Fatal infections (Grade 5) occurred in 4.2% (n=7/167) of patients
Tepkinly must not be administered in patients with active infections
Cases of progressive multifocal leukoencephalopathy (PML), including fatal cases, have been reported in patients treated with epcoritamab who have also received prior treatment with other immunosuppressive medications. If neurological symptoms suggestive of PML occur during epcoritamab therapy, treatment with epcoritamab should be discontinued and appropriate diagnostic measures initiated.1
- Exercise caution when considering the use of Tepkinly in patients with a history of recurring or chronic infections, with underlying conditions that may predispose to infections or who have had significant prior immunosuppressive treatment.
- Patients should be monitored for signs and symptoms of infection before and after Tepkinly administration, and treated appropriately.
- In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines.
- Tepkinly must not be administered in patients with active infections.
- Cases of progressive multifocal leukoencephalopathy (PML), including fatal cases, have been reported in patients treated with epcoritamab who have also received prior treatment with other immunosuppressive medications. If neurological symptoms suggestive of PML occur during epcoritamab therapy, treatment with epcoritamab should be discontinued and appropriate diagnostic measures initiated.
Recommended dosage modifications for adverse reactions other than ICANS and CRS1
‡Based on National Cancer Institute Common Terminology Criteria for Adverse Events.
Tumour lysis syndrome (TLS)1
TLS occurred in 1.8% (n=3/167) of patients. There was one patient who experienced onset on Day 14 with resolution on Day 17. Two additional patients experienced onset on Day 8 and Day 33 and both events were ongoing at the time of death; the deaths were due to disease progression.
Patients at an increased risk for TLS are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs or symptoms of TLS, especially patients with high tumour burden or rapidly proliferative tumours, and patients with reduced renal function. Patients should be monitored for blood chemistries and abnormalities should be managed promptly.
No new ICANS, CRS, or clinical TLS events occurred during extended follow-up of the NHL-1 trial; median follow-up time 25.1 months (95% CI, 24.0-26.0).3
Tumour Flare1
Tumour flare occurred in 3.0% (n=5/167) of patients, all of which were Grade 2. The median time to onset was 17 days (range 9 to 34 days), and median duration was 15.5 days (range 1 to 50 days).
Manifestations could include localised pain and swelling. Consistent with the mechanism of action of Tepkinly, tumour flare is likely due to the influx of T-cells into tumour sites following epcoritamab administration.
There are no specific risk factors for tumour flare that have been identified; however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumour flare in patients with bulky tumours located in close proximity to airways and/or a vital organ. Patients treated with Tepkinly should be monitored and evaluated for tumour flare at critical anatomical sites.
*One patient (0.6%) experienced a fatal adverse reaction (ICANS).2
†Actual EPCORE™ NHL-1 study start date: June 26, 2018. Estimated Primary Completion Date: January 2025.5
aPneumonia includes COVID-19 pneumonia and pneumonia.
bUpper respiratory tract infection includes laryngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, rhinovirus infection, and upper respiratory tract infection.
cNeutropenia includes neutropenia and neutrophil count decreased.
dAnaemia includes anaemia and serum ferritin decreased.
eThrombocytopenia includes platelet count decreased and thrombocytopenia.
fCRS and ICANS events were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
gTumour Lysis Syndrome was graded based on Cairo-Bishop.
hAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.
iRash includes rash, rash erythematous, rash maculo-papular, and rash pustular.
jFatigue includes asthenia, fatigue, and lethargy.
kInjection site reactions include injection site bruising, injection site erythema, injection site hypertrophy, injection site inflammation, injection site mass, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, and injection site urticaria.
lPyrexia includes body temperature increased and pyrexia.
mOedema includes face oedema, generalized oedema, oedema, oedema peripheral, and peripheral swelling.
nCRS graded according to ASTCT consensus criteria.
oIf Grade 2 or 3 CRS occurs with the second full dose or beyond, administer CRS prophylaxis with each subsequent dose until Tepkinly dose is given without subsequent CRS (of any grade).
pICANS graded according to ASTCT ICANS Consensus Grading.
qICANS grade is determined by the most severe event (ICE score, level of consciousness, seizures, motor findings, raised ICP/cerebral oedema) not attributable to any other cause.
rIf patient is arousable and able to perform ICE Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point; and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.
sRiegler L et al (2019).
Abbreviations
ASTCT=American Society for Transplantation and Cellular Therapy; BiPAP=bilevel positive airway pressure; C1D1=cycle 1, day 1; C1D8=cycle 1, day 8; C1D15=cycle 1, day 15; C1D22=cycle 1, day 22; C2D1+=cycle 2, days 1+; CPAP=continuous positive airway pressure; CRS=cytokine release syndrome; DLBCL=diffuse large B-cell lymphoma; ICANS=immune effector cell-associated neurotoxicity syndrome; ICE=immune effector cellassociated encephalopathy; ICP=intracranial pressure; IV=intravenous; MedDRA=Medical Dictionary for Regulatory Activities; NHL=non-Hodgkin lymphoma; SI=serious infection; TLS=tumour lysis syndrome.
By clicking the link above, you will leave the AbbVie Pro website and be taken to the eMC PI portal website.
UK-EPCOR-240400. Date of preparation: December 2024.
Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.
Adverse events should also be reported to AbbVie on GBPV@abbvie.com
