Tepkinly is now
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 now 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 EPCORE^TM 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 months).¹

For full safety information, please refer to the NI SmPC

The most common adverse reactions (≥ 20%) of any grade were:

• CRS
• Fatigue
• Neutropenia
• Injection site reactions
• Musculoskeletal pain
• Abdominal pain
• Pyrexia
• Nausea
• Diarrhoea

Serious adverse reactions occurred in 52% (n=87/167) of patients. The most frequent serious adverse reaction (≥ 10%) was cytokine release syndrome (31%, n=52/167).
4.2% (n=7/167) of patients experienced a fatal adverse reaction (ICANS in 0.6% (n=1/167) of patients, viral infections in 1.8% (n=3/167) of patients and pneumonia in 1.8% (n=3/167) of patients).

Tepkinly has a generally manageable safety profile¹

6.6% of patients discontinued subcutaneous Tepkinly due to adverse reactions¹

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 Incidence
CRS Management

CRS events in the EPCORE^TM NHL-1 trial^1,2

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)

Frequency of CRS events by dosing period¹

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 100% (n=85/85)¹

Median duration of CRS events was 2 days (range: 1-27 days)

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 grade^1,2

Management of CRS while using Tepkinly¹

^vDexamethasone should be administered at 10-20 mg per day (or equivalent).
^wTocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg per dose). Repeat tocilizumab after at least 8 hours as needed. Maximum of 2 doses in a 24-hour period.
^aaDexamethasone should be administered at 10-20 mg intravenously every 6 hours.

See bottom of this page for other footnotes.

ICANS Incidence
ICANS Management

ICANS occurrence in EPCORE™ NHL-1 trial^1,3

ICANs occurred in 6% (n=10/167) of patients¹

Frequency of ICANS by grade

The median time to first ICANS onset from the start of Tepkinly treatment was 16.5 days (range: 8-141 days)
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)

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

Management of ICANS while using Tepkinly¹

^aeDexamethasone should be administered at 10 mg intravenously every 12 hours.
^afDexamethasone 10-20 mg intravenously every 12 hours.
^agDexamethasone 10-20 mg intravenously every 6 hours.

See bottom of this page for other footnotes.

Serious Infections
Serious Infections Management

Serious infections of any grade occurred in 25% (n=42/167) of patients treated with Tepkinly¹

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 from start of epcoritamab treatment was 56 days (range: 4-631 days)
Median duration of serious infection was 15 days (range 4-125 days)
Fatal infections (Grade 5) occurred in 4.2% (n=7/167) of patients

Administration of Tepkinly should be avoided in patients with clinically significant active systemic infections.

As appropriate, prophylactic antimicrobials should be administered prior to and during treatment with Tepkinly.
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.

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.

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 2025.⁴
^aViral infection includes asymptomatic COVID-19, COVID-19, cytomegalovirus infection, cytomegalovirus infection reactivation, gastroenteritis viral, herpes simplex, herpes zoster, and oral herpes.
^bPneumonia includes COVID-19 pneumonia and pneumonia.
^cUpper respiratory tract infection includes laryngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, rhinovirus infection, and upper respiratory tract infection.
^dFungal infection includes candida infection, oesophageal candidiasis, and oral candidiasis.
^eSepsis includes bacteraemia, sepsis, and septic shock.
^fNeutropenia includes neutropenia and neutrophil count decreased.
^gAnaemia includes anaemia and serum ferritin decreased.
^hThrombocytopenia includes platelet count decreased and thrombocytopenia.
ⁱLymphopenia includes lymphocyte count decreased and lymphopenia.
^jCRS and ICANS adverse reactions were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
^kTumour Lysis Syndrome was graded based on Cairo-Bishop.
^lCardiac arrhythmias include bradycardia, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, and tachycardia.
^mAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.
ⁿRash includes rash, rash erythematous, rash maculo-papular, and rash pustular.
^oMusculoskeletal pain includes back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain, pain in extremity, and spinal pain.
^pFatigue includes asthenia, fatigue, and lethargy.
^qInjection 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.
^rPyrexia includes body temperature increased and pyrexia.
^sOedema includes face oedema, generalised oedema, oedema, oedema peripheral, and peripheral swelling.
^tBlood sodium decreased includes blood sodium decreased and hyponatraemia.
^uCRS graded according to ASTCT consensus criteria.
^xLow-flow oxygen is defined as oxygen delivered at < 6 L/minute.
^yRiegler L et al. (2019).
^zHigh-flow oxygen is defined as oxygen delivered at ≥ 6 L/minute.
^abICANS graded according to ASTCT ICANS Consensus Grading.
^acICANS 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.
^adIf patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (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.

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.

References

Tepkinly NI Summary of Product Characteristics.
Thieblemont C et al. J Clin Oncol. 2022; 41(12): 2238-47.
Thieblemont C et al. J Clin Oncol. 2022; 41(12): 2238-47. (Supplementary material).
First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma (EPCORE™ NHL-1). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03625037 (Accessed March 2024).