Loncastuximab tesirine interacts in the following cases:
No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN or total bilirubin >1 to 1.5 × ULN and any AST).
Loncastuximab tesirine has not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN and any AST).
In patients with hepatic impairment, monitoring for adverse reactions is recommended.
Loncastuximab tesirine has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min). The effect of severe renal impairment, and end-stage renal disease, with or without haemodialysis, on loncastuximab tesirine pharmacokinetics is unknown. Additional monitoring for adverse reactions may be warranted in these patients when loncastuximab tesirine is administered.
Based on the results from animal studies, loncastuximab tesirine may impair male fertility. Therefore, men being treated with this medicine should be advised to consider having sperm samples preserved and stored before initiating treatment.
There are no data on the use of loncastuximab tesirine in pregnant women. No animal reproduction studies were conducted with loncastuximab tesirine. Loncastuximab tesirine may cause embryo-foetal toxicity when administered to a pregnant woman, because it contains a genotoxic compound (SG3199) and affects actively dividing cells. Loncastuximab tesirine is not recommended during pregnancy unless the potential benefit for the woman outweighs the potential risk to the foetus. Loncastuximab tesirine is not recommended in women of childbearing potential not using contraception.
Pregnancy testing is advised prior to initiating loncastuximab tesirine.
There is no data on the presence of loncastuximab tesirine or SG3199 in human milk, the effects on the breastfed child, or milk production. A risk for breast-feeding children cannot be excluded. Breast-feeding should be discontinued during treatment with loncastuximab tesirine and for at least 3 months after the last dose.
Women of childbearing potential should be advised to use effective contraception during treatment with loncastuximab tesirine and for at least 10 months after the last dose.
Because of the potential for genotoxicity, men with partners of childbearing potential should be advised to use effective contraception during treatment with loncastuximab tesirine and for at least 7 months after the last dose.
Based on the results from animal studies, loncastuximab tesirine may impair male fertility. Therefore, men being treated with this medicine should be advised to consider having sperm samples preserved and stored before initiating treatment.
Loncastuximab tesirine has no or negligible influence on the ability to drive and use machines. However, fatigue has been reported in patients taking loncastuximab tesirine and this should be taken into account when driving or using machines.
The most frequent reported adverse reactions with loncastuximab tesirine were γ-glutamyltransferase increased (35.8%), neutropenia (34.9%), fatigue (30.2%), anaemia (28.8%), thrombocytopenia (28.4%), nausea (26.5%), peripheral oedema (23.3%), and rash (20.0%).The most frequent severe adverse reactions (≥ Grade 3) were neutropenia (24.2%), γ-glutamyltransferase increased (17.2%), thrombocytopenia (15.8%), anaemia (11.6%) and infections (9.8%).
The most frequent serious adverse reactions were febrile neutropenia (3.3%), abdominal pain, dyspnoea and pleural effusion (1.9% each). Lung infection was identified as an adverse reaction associated with fatal outcome (0.5%).
The most frequent adverse reactions leading to treatment withdrawal were γ-glutamyltransferase increased (8.8%), peripheral oedema (2.8%), thrombocytopenia (1.9%), pleural and pericardial effusion (1.4% each).
The frequency of dose modification or interruption due to adverse reactions was 47.4%. The most frequent adverse reaction leading to dose reduction was γ-glutamyltransferase increased (3.3%), and the most frequent adverse reactions leading to dose delay were γ-glutamyltransferase increased (17.7%), neutropenia (11.2%) and thrombocytopenia (7.9%).
The frequencies of adverse reactions are based on 215 patients with relapsed or refractory DLBCL, who received loncastuximab tesirine alone as an intravenous infusion at the recommended initial dose (0.15 mg/kg) in two monotherapy studies, of whom 145 patients participated in the Phase 2 pivotal study ADCT-402-201 (LOTIS-2) and 70 patients participated in the Phase 1 study (ADCT-402-101). These patients were exposed to loncastuximab tesirine during a median of 45 days (range 1 to 569 days).
Unless otherwise stated, the frequencies of adverse reactions are based on all-cause adverse event frequencies in the clinical studies, where a proportion of the events for an adverse reaction may have other causes than the medicinal product, such as the disease, other medicinal products or unrelated causes.
Adverse reactions are presented according to the MedDRA system organ class (SOC) and classified, by frequency, as 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), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented by seriousness from highest to lowest.
Adverse reactions reported for loncastuximab tesirine in adult patients with relapsed or refractory DLBCL:
| MedDRA SOC | Very common | Common | Uncommon |
|---|---|---|---|
| Infections and infestations | Pneumoniaa (includes lung infection) Upper respiratory tract infection Lower respiratory tract infection | ||
| Blood and lymphatic system disorders | Anaemia Neutropenia Thrombocytopenia | Febrile neutropenia | |
| Metabolism and nutrition disorders | Decreased appetite | Fluid retention | Fluid overload |
| Nervous system disorders | Lethargy | ||
| Cardiac disorders | Pericardial effusion | Pericarditis | |
| Respiratory, thoracic and mediastinal disorders | Pleural effusion Dyspnoeab | ||
| Gastrointestinal disorders | Abdominal painc Diarrhoea Nausea Vomiting Constipation | Ascites | |
| Skin and subcutaneous tissue disorders | Rash Pruritus Erythema | Photosensitivity reaction Maculopapular rash Skin hyperpigmentation Pruritic rash Swelling face Bullous dermatitis | Pustular rash |
| Musculoskeletal and connective tissue disorders | Neck pain Pain in extremity Back pain Musculoskeletal pain Myalgia Musculoskeletal chest pain | Musculoskeletal discomfort Limb discomfort | |
| General disorders and administration site conditions | Oedema peripheral Fatigue | Face oedema Asthenia Peripheral swelling Swelling Non-cardiac chest pain | Generalised oedema |
| Investigations | γ-glutamyltransferase increased Aspartate aminotransferase increased Alanine aminotransferase increased Blood alkaline phosphatase increased |
Serious effusion and oedema occurred in patients treated with loncastuximab tesirine. Grade ≥3 oedema and effusion occurred in 5.6% of patients. Grade 3 or 4 pericardial effusion occurred in 1.4% of patients. Grade 3 pleural effusion occurred in 2.8%, Grade 3 peripheral oedema and ascites in 1.4% each, and Grade 3 peripheral swelling in 0.5% of patients. Effusion and oedema led to discontinuation of treatment in 5.1% of patients. There were no fatal events of effusion or oedema. Median time to onset for Grade ≥3 effusion and oedema was 115 days and 101 days, respectively.
Treatment with loncastuximab tesirine can cause severe myelosuppression. Grade 3 or 4 neutropenia occurred in 24.2%, Grade 3 or 4 thrombocytopenia in 15.8%, and Grade 3 or 4 anaemia in 11.6% of patients. Febrile neutropenia occurred in 3.3% of patients. Thrombocytopenia and neutropenia led to discontinuation of treatment in 1.9% and 0.5% of patients, respectively. No patients discontinued treatment due to anaemia. Median time to onset for Grade 3 or 4 neutropenia, thrombocytopenia and anaemia was 36.0 days, 28.5 days, and 22.0 days, respectively.
Fatal and serious infections, including opportunistic infections, occurred in patients treated with loncastuximab tesirine. Grade ≥3 infections occurred in 9.8% of patients with an associated fatal infection in 0.5% of patients. Infections led to discontinuation of treatment in 0.9% of patients.
Severe cutaneous reactions occurred in patients treated with loncastuximab tesirine. Grade 3 cutaneous reactions occurred in 3.7% and included photosensitivity reaction (1.4%), rash (0.9%), rash pustular (0.5%), rash maculo-papular (0.5%), and erythema (0.5%). There were no Grade 4 or Grade 5 cutaneous reactions. Three (3) patients (1.4%) discontinued loncastuximab tesirine due to Grade 1-2 cutaneous reactions, and no patients discontinued loncastuximab tesirine due to a severe cutaneous reaction. Median time to onset for Grade 3 photosensitivity reactions was 32.0 days and for Grade 3 non-photosensitivity cutaneous reactions was 56.0 days.
Serious cutaneous reactions have been reported in patients treated with loncastuximab tesirine. In clinical studies with loncastuximab tesirine oral and topical corticosteroids and anti-pruritic therapy were used to treat cutaneous reactions.
Abnormal liver function tests of severity Grade ≥3 occurred in 19.5% of patients, with Grade 3 or 4 γ-glutamyltransferase (GGT) increased in 17.2% of patients. GGT increase resulted in dose delay, dose reduction, and treatment withdrawal in 17.7%, 3.3%, and 8.8% of patients, respectively. Grade 3 alanine aminotransferase increased occurred in 2.8%, blood alkaline phosphatase increased in 1.4%, and aspartate aminotransferase increased in 0.9% of patients. Increased blood bilirubin was noted in 2.8% of patients, with Grade 3 occuring in 1.4% of patients.
The following adverse drug reactions have been identified from the post-marketing reports for loncastuximab tesirine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: telangiectasia, blister, rash vesicular (frequency unknown).
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