FDA Approves Isatuximab Combination for Previously Treated Multiple Myeloma

The FDA approved isatuximab-irfc (Sarclisa), in combination with pomalidomide (Pomalyst) and dexamethasone (Ozurdex), for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. 

Isatuximab received orphan drug designation, and the approval was based on the results of a clinical trial involving 307 patients with relapsed and refractory multiple myeloma who received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor. 

“Targeting cells has led to the development of important oncology treatments. While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release. “In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy.” 

In the trial, half of the patients were given isatuximab in combination with pomalidomide and low-dose dexamethasone and the other half received only pomalidomide and low-dose dexamethasone. The efficacy of isatuximab was based on progression-free survival (PFS), and those who received isatuximab in combination with pomalidomide and low-dose dexamethasone demonstrated improvement in PFS with a 40% reduction in the risk of disease progression or death compared to the participants who only received pomalidomide and dexamethasone. 

In the isatuximab combination arm, patients also had an overall response rate (ORR) of 60.4%. Comparatively, the patients who only received pomalidomide and low-dose dexamethasone had an overall response rate of 35.3%. 

Common adverse events for patients taking isatuximab were neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia. 

Isatuximab was also found to cause IV infusion-related reactions. Should patients report grade 3 or higher reactions, the FDA indicated that the infusion should be permanently discontinued, and healthcare professionals should institute proper medical management. Additionally, given that isatuximab can cause neutropenia, health care professionals should monitor a patient’s complete blood cell count periodically during treatment, as well as monitor patients with neutropenia for signs of infection. 

In a controlled clinical trial group of patients with multiple myeloma receiving isatuximab, higher incidences of second primary malignancies were observed; therefore, healthcare professionals should monitor patients for the development of a second primary malignancy when taking isatuximab. 

Moreover, laboratory test interference may occur with isatuximab. The FDA recommended that blood banks be informed that patients are receiving isatuximab because the drug could interfere with certain tests that done specifically by blood banks for patients needing a blood transfusion. Health care professionals should also type and screen patients prior to starting treatment. Further, isatuximab may interfere with the assays used to monitor M-protein, which might impact the determination of complete response. 

According to the FDA, pregnant women should be advised that isatuximab may cause harm to a developing fetus and should not be taken while pregnant. Additionally, women planning to become pregnant should use effective contraceptives during and for at least 5 months after treatment.

References:

FDA Approves New Therapy for Patients with Previously Treated Multiple Myeloma [news release]. Published March 2, 2020. fda.gov/news-events/press-announcements/fda-approves-new-therapy-patients-previously-treated-multiple-myeloma. Accessed March 2, 2020.