Isatuximab Demonstrates Significant PFS Among Patients With Multiple Myeloma

Multiple myeloma, a relatively uncommon blood-related cancer which affects plasma cells, will be diagnosed in approximately 34,470 adults in the United States this year.^1,2 About 1 in 132 (0.76%) people will get multiple myeloma in their lifetime.

Further, the American Cancer Society³ estimates 12,640 deaths to occur related to multiple myeloma—7090 in men and 5500 in women.

Multiple myeloma is characterized by its attack on healthy plasma cells, causing them to change or grow exponentially which can lead to bone lesions and other symptoms.¹ When abnormal plasma cells grow, they can suppress the growth of other cells in the bone marrow, such as red and white blood cells, and platelets, reducing a patient’s natural immunities.¹

The plasma cells make an abnormal protein (antibody) known by several different names, including monoclonal immunoglobulin, monoclonal protein (M-protein), M-spike, or paraprotein,³ which can be detected via blood and urine tests to make a complete diagnosis.¹

The associated economic burden of multiple myeloma on both patients and the health care system is considered substantial as treatments often have to be specifically targeted and the tendency for a patient to relapse or become resistant to certain therapies

Treatment regimens are typically determined by a multidisciplinary team and are dependent on whether a patient is experiencing symptoms—what stage their cancer has progressed to—and their overall health. As there is no cure, primary goals of multiple myeloma treatment are to eliminate the abnormal cells, control tumor growth, limit pain, and manage quality of life.

Treating multiple myeloma includes induction therapy, consolidation, and maintenance therapy.¹ Typical medication types include: chemotherapy, targeted therapy, immunomodulatory drugs, steroids, bone-modifying drugs, and immunotherapy.

Per the National Comprehensive Cancer Network Guidelines, chemotherapy combined with targeted therapy or steroids is often recommended. However, “researchers have showed genetic abnormalities or epigenetic aberrations that affect the patterns of DNA methylation and histone modifications of genes, mainly tumor suppressors, play a vital role in drug resistance in multiple myeloma resistance.”⁴

Because of the resistance factors, patients may change medications or therapy regimens several times throughout the cancer care journey, with doctors running tests on specific cancer cells to determine the most effective treatment.

Targeted therapy options for multiple myeloma include: proteasome inhibitors (bortezomib, carfilzomib, and ixazomib); histone deacetylase inhibitors (Panobinostat); nuclear export inhibitors (Selinexor), B-cell maturation antigen targeting agents; and monoclonal antibodies (elotuzumab, daratumumab, isatuximab-irfc, and other combinations).⁴

With the tendency to cause resistance to medications, demonstrated clinical benefit of therapy options for third or potentially fourth line options are critical to improving patient outcomes.

On April 1, 2021, the FDA approved monoclonal antibody isatuximab-irfc in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who previously received 1 to 3 prior lines of therapy.^5-7

The approval for isatuximab-irfc was based on a multicenter, multinational, randomized, open-label, two-arm, phase 3 IKEMA trial of 302 patients which resulted in a 45% reduction in disease progression.⁵

New progression free survival (PFS) data, published in May 2022,⁶ shows “isatuximab in combination with carfilzomib and dexamethasone demonstrated a median progression free survival (mPFS) of 35.7 months (HR 0.58; 95% CI: 25.8 to 44.0; n=179), compared to 19.2 months in patients treated with carfilzomib and dexamethasone alone (95% CI: 15.8 to 25.1; n=123), as evaluated by an Independent Review Committee.”

The updated analysis shows median PFS increased from 19.2 months to 35.7 months when isatuximab was added to carfilzomib and dexamethasone.⁶

Additionally, “A PFS analysis following the [FDA’s] recommendations on censoring rules, as applied in the approved US prescribing information, showed an median PFS of 41.7 months for [isatuximab] added to [carfilzomib and dexamethasone] compared to 20.8 months in patients treated with [carfilzomib and dexamethasone] alone (HR 0.59; 95% CI: 27.1 to Not Calculable [NC]),” according to Sanofi in a press release.⁶

The phase 3 trials evaluating isatuximab in combination with current standards of treatment for multiple myeloma are ongoing.