Reducing Disease Progression, Burden for Patients With Multiple Myeloma

Multiple myeloma is a relatively rare blood cancer that effects a patient’s plasma, causing build up in the bone marrow and potentially tumor growth. Although it is rarer than most, it is the second most common blood cancer after non-Hodgkin lymphoma—effecting more than 130,000 adults in the United States.^1-3

According to data from American Society of Clinical Oncology (ASCO), an estimated 32,270 adults (17,530 men and 14,740 women) in the United States will be diagnosed with multiple myeloma in 2020. It is estimated to cause more than 12,000 deaths.¹

The exact cause of multiple myeloma is unknown, but age is the most significant risk factor for patients as it is typically developed in people older than 45 years. Men are twice as likely to be affected. It has also been found that multiple myeloma is diagnosed twice as frequently for Black patients than White.²

Diagnosis Guidelines

“The majority of patients with myeloma present with symptoms related to organ involvement, including hypercalcemia, renal insufficiency, anemia, and bone lesions (known as calcium, renal failure, anemia, and bone lesions [CRAB] symptoms).”⁴ 

A small percentage of patients with multiple myeloma present as asymptomatic but found to have abnormal blood and/or urine tests that lead to the diagnosis. According to treatment and diagnosis guidelines published by ASCO, “The diagnosis requires the presence of clonal plasma cells in the bone marrow or in a biopsy-proven bone or extramedullary plasmacytoma. The specific diagnostic criteria for active multiple myeloma have recently been updated by the International Myeloma Working Group and include the presence of clonal plasma cells plus CRAB features or one of three new biomarkers.”⁵

These additional diagnostic criteria help providers define more at-risk patient populations, start therapy options sooner, and reduce disease progression at a faster rate. 

Stages and Treatment Options

Treatment for patients with multiple myeloma varies based on the level of disease progression. Therapy options most commonly include local treatments (where tumors are treated without effecting the rest of the body), systemic treatments (including oral and intravenous drugs), stem cell transplants, and combination therapies.⁵

For patients with solitary plasmacytomas, radiation therapy has proven most successful. For these patients and patients with smoldering multiple myeloma, chemotherapy has also been utilized.⁵

“Based on how abnormal the plasma cells look under the microscope and the levels of immunoglobulins, some patients with smoldering multiple myeloma have a high risk of progressing to active myeloma,” explained the American Cancer Society. “In one study, treating these patients with lenalidomide (Revlimid) and dexamethasone before they developed symptoms or problems helped them live longer.”⁵

For patients with active, symptomatic myeloma, combination therapies, often including two or three different therapeutics have proven successful at reducing disease progression. Depending on an individual patient’s treatment plan, whether they are eligible for a stem cell transplant, and kidney function, the most commonly used drugs are bortezomib, lenalidomide, and dexamethasone.⁵ 

“Combinations containing bortezomib are especially helpful in patients with kidney problems and those whose myeloma cells contain certain high-risk chromosome abnormalities,” stated the American Cancer Society.⁵

On March 2, 2020, isatuximab-irfc, a monoclonal antibody that binds to the CD38 receptor, received FDA approval for the treatment of adults with relapsed refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

According to recent trials, isatuximab-irfc (Sarclisa) in combination with pomalidomide and dexamethasone (pom-dex) significantly reduced the risk of disease progression or death by 40% compared to pom-dex alone in a pivotal trial.³

"Most patients with multiple myeloma unfortunately relapse and become refractory to currently available therapies. Isatuximab-irfc used in combination with pomalidomide and dexamethasone offers an important new treatment option for patients in the United States living with this incurable disease," said Paul Richardson, MD, principal investigator of ICARIA-MM, and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in a press release. "The pivotal ICARIA-MM trial was the first phase 3 study of a CD38 antibody in combination with pom-dex to present results demonstrating significant clinical benefit in this setting. The study enrolled a broad population of patients with relapsed and refractory multiple myeloma that is particularly difficult to treat and with poor prognosis, which is reflective of real-world practice."³

Cost Burden

According to Sanofi, isatuximab-irfc can be administered for a 28-day treatment cycle either intravenously at 10 mg/kg, in combination with pom-dex, every week for 4 weeks and then every 2 weeks, until disease progression or unacceptable toxicity. In terms of cost burden, the US list price is $650 per 100-mg vial and $3250 per 500-mg vial.³

“For a typical patient in the U.S., between 70-80 kg (154-176 lbs), this correlates to a cost of $5,200 per infusion,” stated Sanofi in a press release. “Actual costs to patients are generally anticipated to be lower as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs.”³

Despite multiple myeloma’s rare diagnosis, it remains one of the costliest cancers to treat due to the influx of orphan drug treatments and combination therapies. 

References 

1. Multiple Myeloma-Statistics. Cancer.Net. Published July 7, 2020. Accessed October 2, 2020. https://www.cancer.net/cancer-types/multiple-myeloma/statistics
2. Centers for Disease Control and Prevention. Myeloma. CDC.gov. Accessed October 2, 2020. https://www.cdc.gov/cancer/myeloma/index.htm.
3. FDA approves Sarclisa® (isatuximab-irfc) for patients with relapsed refractory multiple myeloma. News release. Sanofi; March 2, 2020. Accessed October 2, 2020.  https://www.news.sanofi.us/2020-03-02-FDA-approves-Sarclisa-R-isatuximab-irfc-for-patients-with-relapsed-refractory-multiple-myeloma  
4. Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228-1263. doi:10.1200/jco.18.02096
5. American Cancer Society. Treating multiple myeloma. Cancer.org. Accessed October 2, 2020. https://www.cancer.org/cancer/multiple-myeloma/treating.html.