Columvi Drug Information
Generic name: GLOFITAMAB
Bispecific CD20-directed CD3 T Cell Engager [EPC]
Uses of Columvi
COLUMVI is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Dosage & Administration of Columvi
Important Dosing Information
Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter. Administer COLUMVI diluted solution via intravenous bag infusion. The 2.5 mg dose may alternatively be administered via intravenous syringe infusion.
COLUMVI should only be administered by a healthcare professional with immediate access to appropriate medical support, including supportive medications to manage severe CRS. Ensure adequate hydration before administering COLUMVI. Premedicate before each dose.
Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 1 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS. CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1. For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next COLUMVI infusion.
Recommended Dosage Pretreatment with Obinutuzumab
Pretreat all patients with a single 1,000 mg dose of obinutuzumab administered as an intravenous infusion on Cycle 1 Day 1, 7 days prior to initiation of COLUMVI (see Table 1 ) to deplete the circulating and lymphoid tissue B cells. Obinutuzumab should be administered as an intravenous infusion at 50 mg/hour. The rate of infusion can be escalated in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
Refer to the obinutuzumab prescribing information for complete dosing information. COLUMVI Step-up Dose Schedule COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment with obinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up dose schedule in Table 1.
Administer premedications for each dose of COLUMVI as described in Table 3. Monitoring for Cytokine Release Syndrome Administer the COLUMVI infusions intravenously in a healthcare setting with immediate access to medical support to manage CRS, including severe CRS. For monitoring after delayed or missed doses of COLUMVI, follow the recommendations in Table 2.
Delayed or Missed Doses If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 2, then resume the treatment schedule accordingly. For repeat of the 2.5 mg dose patients should be hospitalized during and for 24 hours after completion of the COLUMVI infusion. Table 2: Recommendations for Restarting COLUMVI After Dose Delay Administer the following premedications to reduce the risk of CRS and infusion-related reactions.
Table 3: Premedications to be Administered for COLUMVI Infusion Tumor Lysis Syndrome Prophylaxis Before starting COLUMVI, administer anti-hyperuricemics to patients at risk of tumor lysis syndrome, ensure adequate hydration status, and monitor as appropriate. Infection Prophylaxis Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation. Consider prophylaxis for cytomegalovirus infection, pneumocystis jirovecii pneumonia (PJP), and other opportunistic infections in patients at increased risk.
Dosage Modifications for Adverse Reactions
No dosage reduction for COLUMVI is recommended. Cytokine Release Syndrome Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension.
If CRS is suspected, withhold COLUMVI and manage according to the recommendations in Table 4 and current practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or life-threatening cases. Table 4: Recommendations for Management of Cytokine Release Syndrome Withhold COLUMVI and manage per current practice guidelines.
Refer to Table 2 for information on restarting COLUMVI after dose delays. Neurologic Toxicity, Including ICANS Management recommendations for neurologic toxicity, including ICANS, is 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. Table 5: Recommended Dosage Modification for Neurologic Toxicity (Including ICANS) Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline.
Consider the type of neurologic toxicity before deciding to withhold COLUMVI., See Dosage and Administration on restarting COLUMVI after dose delays. Neurologic Toxicity (including ICANS ) s Table 6: Recommended Dosage Modifications for Other Withhold COLUMVI in patients with active infection until the infection resolves. For Grade 4, consider permanent discontinuation of COLUMVI.
Preparation into an Intravenous Bag
This section describes preparation of all doses of COLUMVI into an intravenous bag. For preparation instructions for the 2.5 mg dose into an intravenous syringe, see subsection 2.6. Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion.
Dilution for Intravenous Bag Infusion Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 7 ). Select an appropriate size infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection (see Table 7 ). COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or polyolefin.
Prepare the infusion bag by withdrawing and discarding the volume from the infusion bag according to Table 7. Withdraw the required volume of COLUMVI from the vial(s) using a sterile needle and syringe and dilute into the infusion bag to a final concentration of 0.1 mg/mL to 0.6 mg/mL according to Table 7. Table 7: Dilution of COLUMVI into an intravenous infusion bag Discard any unused COLUMVI left in the vial.
Gently invert the infusion bag to mix the solution, in order to avoid excess foaming. Do not shake.
Preparation of 2.5 mg Dose into an Intravenous Syringe This section describes the alternative method of preparation of the 2.5 mg dose of COLUMVI into an intravenous syringe. For preparation instructions for all doses into an intravenous infusion bag, see subsection 2.5. Withdraw 2.5 mL of COLUMVI from the vial using a sterile needle into a second syringe (see Table 8 ).
Attach a connector to the two syringes and transfer COLUMVI into the 30 mL syringe. The final concentration of COLUMVI should be 0.1 mg/mL. Table 8: Dilution of COLUMVI into an intravenous syringe Disconnect the syringes.
Draw air into the syringe containing the COLUMVI diluted solution and close. Gently invert the syringe to mix the solution, in order to avoid excessive foaming. Do not shake.
Remove air bubbles from the syringe before administration.
Storage and Administration Storage of Diluted Product
Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be stored: Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours, or At room temperature up to 25°C (77°F) for up to 4 hours. Do not freeze the diluted infusion solution.
Discard diluted infusion solution if storage time exceeds these limits. Prime the infusion line with the diluted infusion solution. No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, PE, polybutadiene (PBD), polyetherurethane (PEU), polycarbonate (PC), silicone, polytetrafluoroethylene (PTFE), or acrylonitrile butadiene styrene (ABS), and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.
See Table 1 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours (see Table 4 ). To ensure the entire dose of COLUMVI is administered, replace the empty infusion bag or syringe with an infusion bag or syringe containing 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection connected to the same infusion line.
Continue the infusion at the same rate until the recommended infusion duration is reached according to Table 1. Do not mix COLUMVI with other drugs.
| Treatment Cycle Cycle = 21 days | Day | Dose of COLUMVI | |
|---|---|---|---|
| Day 1 | Obinutuzumab 1,000 mg | ||
| Cycle 1 | Day 8 | Step-up dose 1 | 2.5 mg |
| Day 15 | Step-up dose 2 | 10 mg | |
| Cycle 2 to 12 | Day 1 | 30 mg | |
| Treatment cycle | Day | Dose of COLUMVI | Duration of infusion | |
|---|---|---|---|---|
| Cycle 1 | Day 1 | Obinutuzumab Refer to " Pretreatment with obinutuzumab " described above. | ||
| Day 8 | Step-up dose 1 | 2.5 mg | 4 hours For patients who experience CRS with their previous dose of COLUMVI, the time of infusion may be extended up to 8 hours. | |
| Day 15 | Step-up dose 2 | 10 mg | ||
| Cycle 2 | Day 1 | 30 mg | 4 hours | |
| Cycle 3 to 12 | Day 1 | 30 mg | 2 hours If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours. | |
| Last Dose Administered | Time Since Last Dose Administered | Action for Next Dose(s) Administer premedication as per Table 3 for all patients. |
|---|---|---|
| Obinutuzumab pretreatment (Cycle 1 Day 1) | ≤ 2 weeks | Administer COLUMVI 2.5 mg (Cycle 1 Day 8) Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg dose., then resume the planned treatment schedule. |
| > 2 weeks | Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1). Then administer COLUMVI 2.5 mg (Cycle 1 Day 8) and resume the planned treatment schedule. | |
| COLUMVI 2.5 mg (Cycle 1 Day 8) | ≤ 2 weeks | Administer COLUMVI 10 mg (Cycle 1 Day 15) Patients should be hospitalized during and for 24 hours after completing infusion of the 10 mg dose if CRS occurred during the most recent 2.5 mg dose., then resume the planned treatment schedule. |
| > 2 to ≤ 4 weeks | Repeat COLUMVI 2.5 mg (Cycle 1 Day 8). Then administer COLUMVI 10 mg (Cycle 1 Day 15) and resume the planned treatment schedule. | |
| > 4 weeks | Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1) and COLUMVI 2.5 mg (Cycle 1 Day 8). Then administer COLUMVI 10 mg (Cycle 1 Day 15) and resume the planned treatment schedule. | |
| COLUMVI 10 mg (Cycle 1 Day 15) | ≤ 2 weeks | Administer COLUMVI 30 mg (Cycle 2 Day 1), then resume the planned treatment schedule. |
| > 2 to ≤ 6 weeks | Repeat COLUMVI 10 mg (Cycle 1 Day 15). Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule. | |
| > 6 weeks | Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1), COLUMVI 2.5 mg (Cycle 1 Day 8), and COLUMVI 10 mg (Cycle 1 Day 15). Then administer COLUMVI 30 mg (Cycle 2 Day 1) and resume the planned treatment schedule. | |
| COLUMVI 30 mg (Cycle 2 onwards) | ≤ 6 weeks | Administer COLUMVI 30 mg, then resume the planned treatment schedule. |
| > 6 weeks | Repeat the Cycle 1 regimen described in Table 1: obinutuzumab 1,000 mg pretreatment (Day 1), COLUMVI 2.5 mg (Day 8), and COLUMVI 10 mg (Day 15). Then administer COLUMVI 30 mg (Day 1 of next cycle) and resume the planned treatment schedule. |
| Day of Treatment Cycle | Patients requiring premedication | Premedication | Administration |
|---|---|---|---|
| Cycle 1, Day 8 and Day 15; Cycle 2; Cycle 3 | Dexamethasone 20 mg intravenously If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg intravenously. | Completed at least 1 hour prior to COLUMVI infusion. | |
| All patients | Acetaminophen 500 mg to 1,000 mg orally | At least 30 minutes before COLUMVI infusion. | |
| Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent) | Completed at least 30 minutes before COLUMVI infusion. | ||
| All subsequent infusions | All patients | Acetaminophen 500 mg to 1,000 mg orally | At least 30 minutes before COLUMVI infusion. |
| Antihistamine (diphenhydramine 50 mg orally or intravenously or equivalent) | Completed at least 30 minutes before COLUMVI infusion. | ||
| Patients who experienced any grade CRS with the previous dose | Dexamethasone 20 mg intravenously | Completed at least 1 hour prior to COLUMVI infusion. |
| Grade American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria. | Presenting Symptoms | Actions |
|---|---|---|
| Grade 1 | Temperature ≥ 100.4°F (38°C) Premedication may mask fever. Therefore, if clinical presentation is consistent with CRS, follow these management guidelines. | Withhold COLUMVI and manage per current practice guidelines. If symptoms resolve, restart infusion at a slower rate. Duration of infusion may be extended up to 8 hours, as appropriate for that cycle (see Table 1 ). Ensure CRS symptoms are resolved for at least 72 hours before next dose. Refer to Table 2 for information on restarting COLUMVI after dose delays [see Dosage and Administration (2.2) ]. Consider slower infusion rate for next dose. |
| Grade 2 | Temperature ≥ 100.4°F (38°C) with: Hypotension not requiring vasopressors and/or Hypoxia requiring low-flow oxygen Low-flow oxygen defined as oxygen delivered at < 6 L/minute, high-flow oxygen defined as oxygen delivered at ≥ 6 L/minute. by nasal cannula or blow-by | Withhold COLUMVI and manage per current practice guidelines. If symptoms resolve, restart infusion at a slower rate. Ensure CRS symptoms are resolved for at least 72 hours before next dose. For the next dose, consider a slower infusion rate, monitor more frequently, and consider hospitalization. For recurrent Grade 2 CRS, manage per Grade 3 CRS. |
| Grade 3 | Temperature ≥ 100.4°F (38°C) with: Hypotension requiring vasopressor (with or without vasopressin) and/or Hypoxia requiring high-flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask | Withhold COLUMVI and manage per current practice guidelines, which may include intensive care. Ensure CRS symptoms are resolved for at least 72 hours before next dose. Hospitalize for the next dose, monitor more frequently, and consider a slower infusion rate. For recurrent Grade 3 CRS, permanently discontinue COLUMVI. |
| Grade 4 | Temperature ≥ 100.4°F (38°C) with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or Hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation) | Permanently discontinue COLUMVI and manage per current practice guidelines, which may include intensive care. |
| Adverse Reaction | Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03., Based on ASTCT 2019 grading for ICANS. | Actions |
|---|---|---|
| Grade 1 | Continue COLUMVI and monitor neurologic toxicity symptoms. If ICANS, manage per current practice guidelines. | |
| Grade 2 | Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline. Consider the type of neurologic toxicity before deciding to withhold COLUMVI., See Dosage and Administration (2.2) on restarting COLUMVI after dose delays. Provide supportive therapy, and consider neurologic evaluation. If ICANS, manage per current practice guidelines. | |
| Neurologic Toxicity (including ICANS ) [see Warnings and Precautions (5.2) ] | Grade 3 | Withhold COLUMVI until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 7 days., Evaluate benefit-risk before restarting COLUMVI. For Grade 3 neurologic events lasting more than 7 days, consider permanently discontinuing COLUMVI. Provide supportive therapy, and consider neurology evaluation. If ICANS, manage per current practice guidelines. |
| Grade 4 | Permanently discontinue COLUMVI. Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines. |
| Adverse Reactions Based on NCI CTCAE, version 4.03. | Severity | Actions |
|---|---|---|
| Infections [see Warnings and Precautions (5.3) ] | Grades 1 – 4 | Withhold COLUMVI in patients with active infection until the infection resolves. See Dosage and Administration (2.2) on restarting COLUMVI after dose delays. For Grade 4, consider permanent discontinuation of COLUMVI. |
| Grade 1 | Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare. | |
| Tumor flare [see Warnings and Precautions (5.4) ] | Grades 2 – 4 | Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment including antihistamine and corticosteroids. Withhold COLUMVI until tumor flare resolves. |
| Neutropenia | Absolute neutrophil count less than 0.5 × 10 9 /L | Withhold COLUMVI until absolute neutrophil count is 0.5 × 10 9 /L or higher. |
| Thrombocytopenia | Platelet count less than 50 × 10 9 /L | Withhold COLUMVI until platelet count is 50 × 10 9 /L or higher. |
| Other Adverse Reactions [see Adverse Reactions (6.1) ] | Grade 3 or higher | Withhold COLUMVI until the toxicity resolves to Grade 1 or baseline. |
| Dose of COLUMVI | Size of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection infusion bag | Volume to be withdrawn and discarded from the infusion bag | Volume of COLUMVI to be added to the infusion bag | Total volume to be infused |
|---|---|---|---|---|
| 2.5 mg | 50 mL | 27.5 mL | 2.5 mL | 25 mL |
| 10 mg | 50 mL | 10 mL | 10 mL | 50 mL |
| 100 mL | 10 mL | 10 mL | 100 mL | |
| 30 mg | 50 mL | 30 mL | 30 mL | 50 mL |
| 100 mL | 30 mL | 30 mL | 100 mL |
| Dose of COLUMVI | Volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to be added to the syringe | Volume of COLUMVI to be added to the syringe | Total volume to be infused |
|---|---|---|---|
| 2.5 mg | 22.5 mL | 2.5 mL | 25 mL |
Side Effects of Columvi
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma Study NP30179 The safety of COLUMVI was evaluated in Study NP30179, a multi-cohort, multicenter, single-arm clinical trial that included 154 adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. The trial required an ECOG performance status of 0 or 1, absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CLcr) ≥ 50 mL/min, and hepatic transaminases ≤ 3 × ULN.
The trial excluded patients with active or previous central nervous system (CNS) lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic hematopoietic stem cell transplantation (HSCT). Patients received pretreatment with a single dose of obinutuzumab on Day 1 of Cycle 1 (seven days prior to start of COLUMVI). Patients received the 30 mg COLUMVI dose by intravenous infusion on Day 1 of subsequent cycles for a maximum of 12 cycles (including step-up dosing).
Each cycle was 21 days. Patients were hospitalized during and for 24 hours following completion of at least the first step-up dose. Of the 154 patients who initiated study treatment, 145 received COLUMVI; nine patients (6%) did not receive COLUMVI due to infection, progressive disease, or patient decision.
Patients received a median of 5 cycles of COLUMVI with 30% receiving all 12 cycles of COLUMVI. The main diagnoses were DLBCL, NOS and LBCL arising from follicular lymphoma. Serious adverse reactions occurred in 48% of patients who received COLUMVI.
Serious adverse reactions in ≥ 2% of patients included CRS, COVID-19 infection, sepsis, and tumor flare. Adverse reactions led to permanent discontinuation of COLUMVI in 7% of patients, including from infection, delirium, neutropenia, and CRS. Adverse reactions led to dose interruptions of COLUMVI in 19% of patients, most frequently (≥ 2%) from neutropenia and thrombocytopenia.
The most common (≥ 20%) adverse reactions, excluding laboratory terms, were CRS, musculoskeletal pain, rash, and fatigue. The most common Grade 3 to 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased. Table 9 summarizes adverse reactions observed in Study NP30179.
Table 9: Select Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179 0 Clinically relevant adverse reactions occurring in < 10% of patients who received COLUMVI included infusion-related reaction, peripheral neuropathy, pneumonia, mental status changes, vomiting, tumor lysis syndrome, febrile neutropenia, upper respiratory tract infection, sepsis, herpes zoster infection, gastrointestinal hemorrhage, tremor, myelitis, and colitis. Table 10 summarizes laboratory abnormalities in Study NP30179. Table 10: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179 Clinically relevant adverse reactions occurring in other clinical trials Immune system disorders: Hemophagocytic Lymphohistiocytosis Infections: Progressive Multifocal Leukoencephalopathy
| Adverse Reactions | COLUMVI N=145 | |
|---|---|---|
| All grades (%) | Grade 3 or 4 (%) | |
| The table includes a combination of grouped and ungrouped terms. Adverse reactions were graded using NCI CTCAE version 4.03, with the exception of CRS, which was graded per ASTCT consensus criteria in most cases. | ||
| Immune system disorders | ||
| Cytokine release syndrome | 70 | 4.1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain Includes musculoskeletal pain, back pain, bone pain, flank pain, myalgia, neck pain, and pain in extremity. | 21 | 2.1 |
| General disorders | ||
| Fatigue Includes fatigue and asthenia. | 20 | 1.4 |
| Pyrexia | 16 | 0 |
| Edema Includes edema, edema peripheral, swelling face, and face edema. | 10 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Rash Includes rash, rash pruritic, rash maculo-papular, dermatitis, dermatitis acneiform, dermatitis exfoliative, erythema, palmar erythema, pruritus, and rash erythematous. | 20 | 1.4 |
| Gastrointestinal disorders | ||
| Constipation | 14 | 0 |
| Diarrhea | 14 | 0 |
| Nausea | 10 | 0 |
| Abdominal pain Includes abdominal pain, abdominal discomfort, and abdominal pain upper. | 10 | 0 |
| Neoplasms | ||
| Tumor flare | 12 | 2.8 |
| Neurologic Disorders | ||
| Headache | 10 | 0 |
| Laboratory Abnormality | COLUMVI The denominator used to calculate the rate varied from 137 to 145 based on the number of patients with a baseline value and at least one post-treatment value. | |
|---|---|---|
| All Grades (%) | Grade 3 or 4 (%) | |
| Hematology | ||
| Lymphocytes decreased | 90 | 83 |
| Hemoglobin decreased | 72 | 8 |
| Neutrophils decreased | 56 | 26 Grade 4 neutrophil decrease occurred in 9% of patients. |
| Platelets decreased | 56 | 8 |
| Chemistry | ||
| Fibrinogen decreased | 84 | 21 |
| Phosphate decreased | 69 | 28 |
| Sodium decreased | 49 | 7 |
| Calcium decreased | 48 | 2.1 |
| Gamma-glutamyl transferase increased | 33 | 9 |
| Potassium decreased | 32 | 6 |
| Uric acid increased | 23 | 23 |
Warnings & Cautions for Columvi
Cytokine Release Syndrome COLUMVI can cause serious and fatal cytokine release syndrome (CRS). The most common manifestations of CRS included fever, tachycardia, hypotension, chills, and hypoxia. With the first step-up dose of COLUMVI, the median time to onset of CRS (from the start of infusion) was 14 hours (range: 5 to 74 hours).
Recurrent CRS occurred in 34% of all patients. Administer COLUMVI in a facility equipped to monitor and manage CRS. Initiate therapy according to the COLUMVI step-up dosing schedule to reduce the risk of CRS, administer pretreatment medications, and ensure adequate hydration.
Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg step-up dose. For subsequent doses, patients who experienced Grade ≥ 2 CRS with the previous infusion should be hospitalized during and for 24 hours after the next COLUMVI infusion. At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold or permanently discontinue COLUMVI based on severity.
If CRS is refractory to management, consider other causes including hemophagocytic lymphohistiocytosis.
Neurologic Toxicity COLUMVI can cause serious and fatal neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity (ICANS). Grade 3 or higher neurologic adverse reactions occurred in 2.1% of patients and included somnolence, delirium, and myelitis. Cases of ICANS of any grade occurred in 4.8% of patients.
Coadministration of COLUMVI with other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity. Optimize concomitant medications and hydration to avoid dizziness or mental status changes. Institute fall precautions as appropriate.
Monitor patients for signs and symptoms of neurologic toxicity, evaluate, and provide supportive therapy; withhold or permanently discontinue COLUMVI based on severity. Evaluate patients who experience neurologic toxicity such as tremors, dizziness, or adverse reactions that may impair cognition or consciousness promptly, including potential neurology evaluation. Advise affected patients to refrain from driving and/or engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurologic toxicity fully resolves.
Serious Infections COLUMVI can cause serious or fatal infections. Febrile neutropenia occurred in 3.4% of patients. COLUMVI can cause progressive multifocal leukoencephalopathy (PML), including fatal cases.
COLUMVI should not be administered to patients with an active infection. Administer antimicrobial prophylaxis according to guidelines. Monitor patients before and during COLUMVI treatment for infection, including for neurologic signs and symptoms of PML, and treat appropriately.
Withhold or consider permanent discontinuation of COLUMVI based on severity.
Tumor Flare COLUMVI can cause serious tumor flare
Manifestations include localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions. Recurrent tumor flare occurred in two (12%) of the affected patients. The median duration was 3.5 days (range: 1 to 35 days).
Patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored closely during initial therapy. Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, and institute appropriate treatment. Withhold COLUMVI until tumor flare resolves.
Embryo-Fetal Toxicity Based on its mechanism of action, COLUMVI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with COLUMVI and for 1 month after the last dose.
Drug Interactions with Columvi
For certain CYP substrates where minimal concentration changes may lead to serious adverse reactions, monitor for toxicities or drug concentrations of such CYP substrates when coadministered with COLUMVI. Glofitamab-gxbm causes the release of cytokines that may suppress the activity of CYP enzymes, resulting in increased exposure of CYP substrates.
Pregnancy Safety for Columvi
Pregnancy Risk Summary Based on its mechanism of action COLUMVI may cause fetal harm when administered to a pregnant woman. There are no available data on the use of COLUMVI in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with glofitamab-gxbm.
Glofitamab-gxbm causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on expression of CD20 on B cells and the finding of B-cell depletion in non-pregnant animals, glofitamab-gxbm can cause B-cell lymphocytopenia in infants exposed to glofitamab-gxbm in-utero. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, COLUMVI has the potential to be transmitted from the mother to the developing fetus.
Advise women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.
Pediatric Use of Columvi
Pediatric Use The safety and efficacy of COLUMVI in pediatric patients have not been established.
Clinical Studies of Columvi
Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma The efficacy of COLUMVI was evaluated in Study NP30179 (NCT03075696), an open-label, multicenter, multicohort, single-arm clinical trial that included patients with relapsed or refractory LBCL after two or more lines of systemic therapy. The trial excluded patients with active or previous CNS lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic HSCT. The cycle length was 21 days.
COLUMVI was administered for up to 12 cycles unless patients experienced progressive disease or unacceptable toxicity. The efficacy population consists of 132 patients with de novo DLBCL, NOS (80%) or LBCL arising from follicular lymphoma (20%) who received at least one dose of COLUMVI. The median number of prior lines of systemic therapy was 3 (range: 2 to 7).
Efficacy was based on objective response rate (ORR) and duration of response (DOR), as determined by an Independent Review Committee (IRC) using the 2014 Lugano criteria. Efficacy results are summarized in Table 12. The median time to first response was 42 days (range: 31 to 178 days).
Among responders, the estimated median follow-up for DOR was 11.6 months. Table 12: IRC-Assessed Efficacy in Patients with Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma 68.5
| Outcome per IRC | COLUMVI N=132 |
|---|---|
| CI = confidence interval; NE = not estimable | |
| Overall Response Rate, n (%) | 74 (56) |
| (95% CI) | (47, 65) |
| Complete Response, n (%) | 57 (43) |
| (95% CI) | (35, 52) |
| Partial Response, n (%) | 17 (13) |
| (95% CI) | (8, 20) |
| Duration of Response From date of first response (PR or CR) until disease progression or death due to any cause. | N = 74 |
| Median DOR, months (95% CI) Kaplan-Meier estimate. | 18.4 (11.4, NE) |
| 9-month estimate, % (95% CI) | 68.5 (56.7, 80.3) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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