Ebvallo

HOS-098435 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most common adverse reactions were pyrexia (31.1%), diarrhoea (26.2%), fatigue (23.3%), nausea (18.4%), anaemia (16.5%), decreased appetite (15.5%), hyponatraemia (15.5%), abdominal pain (14.6%), neutrophil count decreased (14.6%), white blood cell count decreased (14.6%), aspartate aminotransferase increased (13.6%), constipation (12.6%), alanine aminotransferase increased (11.7%), blood alkaline phosphatase increased (11.7%), hypoxia (11.7%), dehydration (10.7%), hypotension (10.7%), nasal congestion (10.7%) and rash (10.7%). The most serious adverse reactions based on post-authorisation data from ongoing clinical trials and postmarketing experience were tumour flare reaction (1%), graft-versus-host disease (4.9%), and cytokine release syndrome (1.3%). Tabulated list of adverse reactions The safety database is comprised of data from 340 patients (EBV+ PTLD and other EBV-associated diseases) from clinical studies, an expanded access protocol, and compassionate use requests. Frequencies of adverse reactions were calculated in 103 patients from the ALLELE study and Study EBV-CTL-201 for which all events (serious and non-serious) were collected. In the rest of the clinical development program, only serious events were collected. Adverse reactions reported from clinical trials and post marketing experience are presented below in Table 2. These reactions are presented by 7 system organ class and by frequency. Frequencies are defined 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); very rare (< 1/10,000). Table 2: Adverse reactions identified with Ebvallo System organ class (SOC) Adverse reaction Frequency Infections and infestations Upper respiratory tract infection Common Skin infection Common Neoplasms benign, malignant and Tumour pain Common unspecified (including cysts and Tumour flare reaction Common polyps) Blood and lymphatic system Anaemia Very common disorders Febrile neutropenia Common Immune system disorders Graft-versus-host diseasea Common Cytokine release syndro

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HOS-098431 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098430 · has-indication-information · PDF-Seite 2

Ebvallo is indicated as monotherapy for treatment of adult and paediatric patients 2 years of age and older with relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) who have received at least one prior therapy. For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate. 2

HOS-098433 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed. Immunosuppressive and cytotoxic therapies Certain concomitant or recently administered medicinal products including chemotherapy (systemic or intrathecal), anti-T-cell antibody-based therapies, extracorporeal photopheresis or brentuximab vedotin could potentially impact the efficacy of Ebvallo. Ebvallo should only be administered after an adequate washout period of such agents. For patients receiving chronic corticosteroid therapy, the dose of these drugs should be reduced as much as is clinically safe and appropriate; recommended no greater than 1 mg/kg per day of prednisone or equivalent. Ebvallo has not been evaluated in patients receiving corticosteroid doses greater than 1 mg/kg per day of prednisone or equivalent. In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate. 6 CD20-targeting antibodies Because in vitro characterisation data demonstrated the absence of CD20 expression on tabelecleucel, it is not expected that anti-CD20 antibody treatments will affect tabelecleucel activity.

HOS-098434 · has-pregnancy-information · PDF-Seite 7

Pregnancy There are no available data with tabelecleucel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with tabelecleucel. It is not known if tabelecleucel has the potential to be transferred to the foetus or can cause foetal harm when administered to a pregnant woman. Ebvallo is not recommended during pregnancy and in women of childbearing potential not using contraception. Pregnant women should be advised on potential risks for the foetus. There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with Ebvallo. Breast-feeding It is unknown whether tabelecleucel is excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding women should be advised of potential risks to the breast-fed child. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from tabelecleucel therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data on the effect of tabelecleucel on fertility.

HOS-098432 · has-warning-information · PDF-Seite 4

Traceability The traceability requirements of cell‐based advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient should be kept for a period of 30 years after expiry date of the product. Tumour flare reaction (TFR) TFR has occurred with Ebvallo use, generally within the first few days after receiving treatment. TFR presents as an acute inflammatory reaction involving tumour sites which may include a sudden and 4 painful increase in the tumour size or enlargement of disease-involved lymph nodes. TFR may mimic progression of disease. Patients with high tumour burden prior to treatment are at risk of severe TFR. Depending on the location of the tumour or lymphadenopathy, complications (e.g. respiratory distress and cognitive disorders) may arise from mass effect, including compression/obstruction of adjacent anatomic structures. Analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) or localised radiotherapy could be considered prior to Ebvallo administration for those patients in whom the location of the tumour could potentially lead to complications. Patients should be closely monitored for signs and symptoms of TFR, especially during the first cycle. Graft-versus-host disease (GvHD) GvHD has been reported after treatment with Ebvallo. This could be related to the decrease or discontinuation of immunosuppressive therapies for the treatment of PTLD rather than to a direct action of Ebvallo. The benefit of treatment with Ebvallo versus the risk of possible GvHD should be considered. Patients should be monitored for signs and symptoms of GvHD, such as skin rash, abnormal liver enzymes in the blood, jaundice, nausea, vomiting, diarrhoea and bloody stools. Solid organ transplant rejection Solid organ transplant rejection has been reported after treatment with Ebvallo. Treatment with Ebvallo may increase the risk of rejection in solid organ transplant recipients. This could be related to the decrease or discontinuation of immunosuppressive therapies for the treatment of PTLD rather than to a direct action of Ebvallo. The benefit of treatment with Ebvallo versus the risk of possible solid organ transplant rejection should be considered prior to the start of treatment. Patients should be monitored for signs and symptoms of solid organ transplant rejection. Bone marrow transplant rejection There is a pote

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