Introduction and Multiple Myeloma Background
SARCLISA Indication and ICARIA-MM Study Design
ICARIA-MM Results: Safety and Efficacy
SARCLISA Dosing and Administration
SARCLISA Patient Support and Summary
Important Safety Information
Question and Answer
Indication and Important Safety Information
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SARCLISA (isatuximab-irfc) is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients.
WARNINGS AND PRECAUTIONS
Infusion-related reactions (IRRs) have been observed in 39% of patients treated with SARCLISA. All IRRs started during the first SARCLISA infusion and resolved on the same day in 98% of the cases. The most common symptoms of an IRR included dyspnea, cough, chills, and nausea. The most common severe signs and symptoms included hypertension and dyspnea.
To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone. Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade 1 or 2 reactions, interrupt SARCLISA infusion and provide appropriate medical support. If symptoms improve, restart SARCLISA infusion at half of the initial rate, with supportive care as needed, and closely monitor patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally. In case symptoms do not improve or recur after interruption, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if a grade 3 or higher IRR occurs and institute appropriate emergency medical management.
SARCLISA may cause neutropenia. Neutropenia (reported as laboratory abnormality) occurred in 96% of patients and grade 3-4 neutropenia occurred in 85% of patients treated with SARCLISA, pomalidomide, and dexamethasone (Isa-Pd). Febrile neutropenia occurred in 12% of patients and neutropenic infections, defined as infection with concurrent grade ≥3 neutropenia, occurred in 25% of patients treated with Isa-Pd. The most frequent neutropenic infections included those of upper respiratory tract (10%), lower respiratory tract (9%), and urinary tract (3%).
Monitor complete blood cell counts periodically during treatment. Consider the use of antibiotics and antiviral prophylaxis during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay SARCLISA dose until neutrophil count recovery to at least 1.0 × 109/L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended.
Second Primary Malignancies
Second primary malignancies were reported in 3.9% of patients in the SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) arm and in 0.7% of patients in the pomalidomide and dexamethasone (Pd) arm, and consisted of skin squamous cell carcinoma (2.6% of patients in the Isa-Pd arm and in 0.7% of patients in the Pd arm), breast angiosarcoma (0.7% of patients in the Isa-Pd arm), and myelodysplastic syndrome (0.7% of patients in the Isa-Pd arm). With the exception of the patient with myelodysplastic syndrome, patients were able to continue SARCLISA treatment. Monitor patients for the development of second primary malignancies.
Laboratory Test Interference
Interference with Serological Testing (Indirect Antiglobulin Test)SARCLISA binds to CD38 on red blood cells (RBCs) and may result in a false positive indirect antiglobulin test (indirect Coombs test). In ICARIA-multiple myeloma (MM), the indirect antiglobulin test was positive during SARCLISA treatment in 67.7% of the tested patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment. Before the first SARCLISA infusion, conduct blood type and screen tests on SARCLISA-treated patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with SARCLISA has already started, inform the blood bank that the patient is receiving SARCLISA and SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices.
Interference with Serum Protein Electrophoresis and Immunofixation Tests
SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the accuracy of the determination of complete response in some patients with IgG kappa myeloma protein.
The most common adverse reactions (≥20%) were neutropenia (laboratory abnormality, 96% Isa-Pd vs 92% Pd), infusion-related reactions (38% Isa-Pd vs 0% Pd), pneumonia (31% Isa-Pd vs 23% Pd), upper respiratory tract infection (57% Isa-Pd vs 42% Pd), and diarrhea (26% with Isa-Pd vs 19% Pd). Serious adverse reactions occurred in 62% of patients receiving SARCLISA. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients.
USE IN SPECIAL POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with Pd, advise lactating women not to breastfeed during treatment with SARCLISA.