Columvi · 4.4 Special warnings and precautions for use · 1

HOS-100019 · has-adverse-reaction-information · PDF-Seite 15

Summary of the safety profile Columvi monotherapy The most common adverse reactions (≥ 20%) were cytokine release syndrome, neutropenia, anaemia, thrombocytopenia, and rash. The most common serious adverse reactions reported in ≥ 2% of patients were cytokine release syndrome (22.1%), sepsis (4.1%), COVID-19 (3.4%), tumour flare (3.4%), COVID-19 pneumonia (2.8%), febrile neutropenia (2.1%), neutropenia (2.1%), and pleural effusion (2.1%). Permanent discontinuation of Columvi due to an adverse reaction occurred in 5.5% of patients. The most common adverse reactions leading to permanent discontinuation of Columvi were COVID-19 (1.4%) and neutropenia (1.4%). Columvi in combination with gemcitabine and oxaliplatin The most common adverse reactions (≥ 20%) were thrombocytopenia, cytokine release syndrome, neutropenia, anaemia, nausea, peripheral neuropathy, diarrhoea, aspartate aminotransferase increased, alanine aminotransferase increased, rash, lymphopenia, pyrexia, and vomiting. The most common serious adverse reactions reported in ≥ 2% of patients were cytokine release syndrome (20.3%), pyrexia (6.4%), pneumonia (5.8%), COVID-19 (5.8%), thrombocytopenia (4.7%), respiratory tract infection (3.5%), sepsis (2.3%), febrile neutropenia (2.3%), and diarrhoea (2.3%). Permanent discontinuation of Columvi due to an adverse reaction occurred in 20.9% of patients. The most common adverse reactions leading to permanent discontinuation of Columvi were COVID-19 (11.6%), sepsis (1.2%), and pneumonitis (1.2%). Tabulated list of adverse reactions Adverse reactions occurring in relapsed or refractory DLBCL patients treated with Columvi monotherapy (n=145) in study NP30179 and from post marketing experience are listed in Table 6. Patients received a median of 5 cycles of Columvi treatment (range: 1 to 13 cycles). 15 Adverse reactions occurring in relapsed or refractory DLBCL patients treated with Columvi in combination with gemcitabine and oxaliplatin (n=172) in study GO41944 (STARGLO) are listed in Table 7. Patients received a median of 11 cycles of Columvi treatment (range: 1 to 13 cycles). The adverse reactions are listed by MedDRA system organ class and categories of frequency. The following categories of frequency have been used: 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) and not known (frequency cannot be estimated f

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HOS-100015 · has-contraindication-information · PDF-Seite 11

Hypersensitivity to the active substance, to obinutuzumab, or to any of the excipients listed in section 6.1. For specific contraindications on obinutuzumab, please refer to the obinutuzumab prescribing information.

HOS-100014 · has-indication-information · PDF-Seite 2

Columvi in combination with gemcitabine and oxaliplatin is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) who are ineligible for autologous stem cell transplant (ASCT). Columvi 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.

HOS-100017 · has-interaction-information · PDF-Seite 14

No interaction studies have been performed. No interactions with Columvi are expected via the cytochrome P450 enzymes, other metabolising enzymes or transporters. The initial release of cytokines associated with the start of Columvi treatment could suppress CYP450 enzymes. The highest drug-drug interaction risk is during the period of one week following each of the first 2 doses of Columvi (i.e., Cycle 1 Day 8 and 15) in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index (e.g., warfarin, cyclosporine). On initiation of Columvi therapy, patients being treated with CYP450 substrates with a narrow therapeutic index should be monitored. The pharmacokinetics (PK) of glofitamab are not affected by co-administration with gemcitabine or oxaliplatin.

HOS-100018 · has-pregnancy-information · PDF-Seite 14

Women of childbearing potential/Contraception Female patients of childbearing potential must use highly effective contraceptive methods during treatment with Columvi and for at least 2 months following the last dose of Columvi. Pregnancy There are no data on the use of Columvi in pregnant women. No reproductive toxicity studies have been performed in animals (see section 5.3). Glofitamab is an immunoglobulin G (IgG). IgG is known to cross the placenta. Based on its mechanism of action, glofitamab is likely to cause foetal B-cell depletion when administered to a pregnant woman. Columvi is not recommended during pregnancy and in women of childbearing potential not using contraception. Female patients receiving Columvi should be advised of the potential harm to the foetus. Female patients should be advised to contact the treating physician, should pregnancy occur. Breast-feeding 14 It is not known whether glofitamab is excreted in human milk. No studies have been conducted to assess the impact of glofitamab on milk production or its presence in breast milk. Human IgG is known to be present in human milk. The potential for absorption of glofitamab and the potential for adverse reactions in the breast-feeding child is unknown. Women should be advised to discontinue breast-feeding during treatment with Columvi and for 2 months after the final dose of Columvi. Fertility No human data on fertility are available. No fertility assessments in animals have been performed to evaluate the effect of glofitamab on fertility (see section 5.3).

HOS-100016 · has-warning-information · PDF-Seite 11

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. CD20-negative disease There are limited data available on patients with CD20-negative DLBCL treated with Columvi and it is possible that patients with CD20-negative DLBCL may have less benefit compared to patients with CD20-positive DLBCL. The potential risks and benefits associated with treatment of patients with CD20-negative DLBCL with Columvi should be considered. Cytokine release syndrome CRS, including life-threatening reactions, has been reported in patients receiving Columvi (see section 4.8). 11 The most common manifestations of CRS were pyrexia, tachycardia, hypotension, chills and hypoxia. Infusion-related reactions may be clinically indistinguishable from manifestations of CRS. Most CRS events occurred following the first dose of Columvi. Elevated liver function tests (AST and alanine transaminase [ALT] > 3  ULN and/or total bilirubin > 2  ULN) concurrent with CRS have been reported after Columvi use (see section 4.8). Patients in studies NP30179 and GO41944 (STARGLO) were pre-treated with obinutuzumab to lower the circulating and lymphoid B cells, 7 days prior to initiation of Columvi therapy. All patients should be premedicated with an anti-pyretic, antihistamine, and a glucocorticoid (see Table 1). At least 1 dose of tocilizumab for use in the event of CRS must be available prior to Columvi infusion at Cycles 1 and 2. Access to an additional dose of tocilizumab within 8 hours of use of the previous tocilizumab dose must be ensured. When Columvi is given as monotherapy, patients must be monitored during all Columvi infusions and for at least 10 hours after completion of the first infusion. When Columvi is given in combination with gemcitabine and oxaliplatin, patients must be monitored during all Columvi infusions and for 4 hours after completion of the first infusion. For complete information on monitoring, see section 4.2. Patients must be counselled to seek immediate medical attention should signs or symptoms of CRS occur at any time (see Patient card below). Patients should be evaluated for other causes of fever, hypoxia and hypotension, such as infections or sepsis. CRS should be managed based on the patient’s clinical presentation and according to the CRS management guidance provided in Table 4 (section

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