COLUMVI CONCENTRATE FOR SOLUTION FOR INFUSION 1MG/ML [SIN16968P]

Product Info

COLUMVI CONCENTRATE FOR SOLUTION FOR INFUSION 1MG/ML

[SIN16968P]

Indication

2.1 THERAPEUTIC INDICATION(S)
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 not candidates for autologous stem cell transplant (ASCT).

Columvi 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. (See 3.1.2 Clinical / Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

Dosing

2.2 DOSAGE AND ADMINISTRATION
General
Columvi therapy should only be administered under the supervision of a healthcare professional experienced in the treatment of cancer patients and who has access to appropriate medical support to manage severe reactions associated with cytokine release syndrome (CRS). 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. See Section 2.4.1 Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Pre-treatment with Obinutuzumab
All patients must receive a single 1000 mg dose of obinutuzumab on Cycle 1 Day 1 (7 days prior to initiation of Columvi treatment); see Table 2, Table 3 and Delayed or Missed Doses. This is to deplete circulating and lymphoid tissue B cells and thereby reduce the risk of CRS.

Obinutuzumab should be administered as an intravenous infusion at 50 mg/h. The rate of infusion can be escalated in 50 mg/h increments every 30 minutes to a maximum of 400 mg/h.

Refer to the obinutuzumab prescribing information for complete information on premedication, preparation, administration, and management of adverse reactions of obinutuzumab.

Premedication and Prophylactic Medications
Cytokine release syndrome prophylaxis
Columvi should be administered to well-hydrated patients. Premedication to reduce the risk of CRS (see Section 2.4.1 Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) is outlined in Table 1.

Infection prophylaxis
Prophylaxis is recommended to reduce the risk of infection (see Section 2.4 Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Consider prophylaxis for cytomegalovirus (CMV), herpes, pneumocystis jirovecii pneumonia, and other opportunistic infections in patients at increased risk (see Section 2.6.1 Description of selected adverse reactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Recommended Dosage
Columvi dosing begins with a step-up dosing schedule (which is designed to decrease the risk of CRS), leading to the recommended dose of 30 mg.

Columvi Monotherapy Dose Step-Up Schedule
Columvi must be administered as an intravenous infusion according to the dose step-up schedule leading to the recommended dosage of 30 mg (as shown in Table 2), after completion of pre-treatment with obinutuzumab on Cycle 1 Day 1. Each cycle is 21 days.

Columvi Dose Step-up Schedule in Combination with Gemcitabine and Oxaliplatin
Columvi must be administered as an intravenous infusion according to the dose step-up schedule leading to the recommended dosage of 30 mg (as shown in Table 3), after completion of pre-treatment with obinutuzumab on Cycle 1 Day 1. Administer Columvi in combination with gemcitabine and oxaliplatin at Cycles 1–8 and as monotherapy at Cycles 9–12. Each cycle is 21 days.

Monitoring after infusion

• When Columvi is given as monotherapy, patients must be monitored for signs and symptoms of potential CRS during infusion and for at least 10 hours after completion of the infusion of the first Columvi dose (2.5 mg on Cycle 1 Day 8).

• When Columvi is given in combination with gemcitabine and oxaliplatin, patients must be monitored for signs and symptoms of potential CRS during all Columvi infusions and for 4 hours after completion of infusion of the first Columvi dose (2.5 mg on Cycle 1 Day 8).

• Patients who experienced Grade ≥ 2 CRS with their previous infusion should be monitored after completion of the infusion. See Table 4.

• Refer to section 2.6.1. Description of selected adverse drug reactions from clinical trials, Cytokine Release Syndrome – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

All patients must be counselled on the risk, signs, and symptoms of CRS and advised to contact the healthcare provider immediately should they experience signs and symptoms of CRS.

Duration of Treatment
Treatment with Columvi monotherapy is recommended for a maximum of 12 cycles or until disease progression or unmanageable toxicity, whichever occurs first.

Treatment with Columvi in combination with gemcitabine and oxaliplatin is recommended for 8 cycles, followed by 4 cycles of Columvi monotherapy for a maximum of 12 cycles of Columvi in total or until disease progression or unmanageable toxicity, whichever occurs first.

Delayed or Missed Doses
During step-up dosing (weekly dosing):

• Following pre-treatment with obinutuzumab, if the Columvi 2.5 mg dose is delayed by more than 1 week, then repeat pre-treatment with obinutuzumab.

• Following Columvi 2.5 mg dose, if there is a Columvi treatment-free interval of 2 to 4 weeks, then repeat glofitamab 2.5 mg dose and resume the planned step-up dosing.

• Following Columvi 2.5mg dose, if there is a Columvi treatment-free interval of more than 4 weeks, then repeat pre-treatment with obinutuzumab and Columvi step-up dosing (see Cycle 1 in Table 2 and Table 3).

• Following Columvi 10 mg dose, if there is a Columvi treatment-free interval of 2 weeks to 6 weeks, then repeat the last tolerated Columvi dose and resume the planned step-up dosing.

• Following Columvi 10 mg dose, if there is a Columvi treatment-free interval of more than 6 weeks, then repeat pre-treatment with obinutuzumab and Columvi step-up dosing (see Cycle 1 in Table 2 and Table 3).

After Cycle 2 (30 mg dose):

• If there is a Columvi treatment-free interval of more than 6 weeks between cycles, then repeat pre-treatment with obinutuzumab and Columvi step-up dosing (see Cycle 1 in Table 2 and Table 3), and then resume the planned treatment cycle (30 mg dose).

Preparation and Administration of Columvi
Preparation
Columvi must be diluted by a healthcare professional using aseptic technique, prior to intravenous administration. See Section 4.2 Special Instructions for Use, Handling, and Disposal – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Administration

• Columvi must be administered as an intravenous infusion through a dedicated infusion line.

• Columvi must not be administered as an intravenous push or bolus.

• Columvi must not be mixed with other drugs.

Dose Modifications
No dose reductions of Columvi are recommended.

Management of Cytokine Release Syndrome
Cytokine release syndrome should be identified based on the clinical presentation (see Section 2.4 Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Patients should be evaluated for other causes of fever, hypoxia, and hypotension, such as infections or sepsis. If CRS is suspected, it should be managed according to the CRS management recommendations based on American Society for Transplantation and Cellular Therapy [ASTCT] consensus grading in Table 4.

Management of Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Management recommendations for neurologic toxicity, including ICANS, are summarized in Table 5. At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding Columvi based on the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care.

2.2.1 Special Dosage Instructions
Pediatric use
The safety and efficacy of Columvi in pediatric patients have not been established.

Geriatric use
No dose adjustment of Columvi is required in patients ≥ 65 years of age. (See Section 2.5 Use in Special Populations and Section 3.2.5 Pharmacokinetics in Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.)

Renal Impairment
No dose adjustment of Columvi is required in patients with mild or moderate renal impairment (CrCL 30 to < 90 mL/min). Columvi has not been studied in patients with severe renal impairment. (See Section 2.5 Use in Special Populations and Section 3.2.5 Pharmacokinetics in Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.)

Hepatic Impairment
No dose adjustment is required in patients with mild hepatic impairment (total bilirubin > upper limit of normal [ULN] to ≤ 1.5 × ULN or aspartate transaminase [AST] > ULN). No specific studies in patients with moderate or severe hepatic impairment have been conducted with Columvi. (See Section 2.5 Use in Special Populations and Section 3.2.5 Pharmacokinetics in Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.)

Contraindications

2.3 CONTRAINDICATIONS
Columvi is contraindicated in patients with a known hypersensitivity to glofitamab or any of the excipients.

Refer to obinutuzumab-specific contraindications in the obinutuzumab prescribing information.