Bringing Advanced Medicines for Multiple Myeloma into Reach for All

Multiple myeloma is a cancer of the bone marrow. It affects plasma cells, which are mature forms of blood cells called B-lymphocytes. In the case of multiple myeloma, abnormal plasma cells build up in the bone marrow, and can cause anemia. In addition, multiple myeloma may cause kidney problems, bone injury and fractures.  

There have been many recent advances in the treatment of multiple myeloma that are enabling people to live longer and higher quality lives with the disease. 

However, those gains have not been distributed equally. In the U.S., according to Dana-Farber research: 

• Black people and Hispanic people are more likely to have a precursor condition of multiple myeloma (an increase in bone marrow plasma cells that increases the risk of cancer) than white people. 

• Black people are twice as likely to be diagnosed with the disease compared to white people and are diagnosed at earlier ages. 

• Black people have not experienced the same survival gains as white people. 

There are many factors that contribute to these disparities. For instance, there may be inherited risk factors that increase the chances of multiple myeloma in individuals of African descent. 

However, the differences in survival largely stem from systemic racism, which has resulted in many Black Americans living with lower socioeconomic status, having less access to high quality medical care, and being less likely to be included in clinical trials. 

“There are so many new medications that are coming out that are very impactful in terms of improved survival,” says Monique Hartley-Brown, MD, MMSc, a physician in the Jerome Lipper Multiple Myeloma Center at Dana-Farber Brigham Cancer Center. “But it’s almost as if you’re putting these medicines on a floating shelf that is out of reach of many individuals.” 

At Dana-Farber, there are several efforts underway to lower that shelf so that everyone can benefit from medical advances. 

“Ultimately, our health care system is supposed to be helping all humans and not separating them out,” says Hartley-Brown. “We need to look at these differences and understand why they exist, and then we need to focus our solutions on developing systems that serve everyone.” 

Getting at the roots of disparities 

A key first step to reducing disparities is to reduce time to diagnosis of multiple myeloma and ensure patients receive the best possible first line of therapy for the form of myeloma they have, be it considered standard risk disease or high-risk disease. 

According to Hartley-Brown, studies of the diagnosis of multiple myeloma in the real world suggest that it might take more than 3 months for a patient who is suspected of having myeloma to be seen by an oncologist.  

“Delays in diagnosis and treatment can increase morbidity and mortality,” says Hartley-Brown. 

For instance, patients may develop more bone lesions, bone fractures, fatigue, abdominal pain, and kidney disease. The longer the disease progresses without treatment, the more likely it is that the patient will suffer organ damage. 

Learn more about how multiple myeloma is diagnosed at Dana-Farber. 

Learn more about how multiple myeloma is treated at Dana-Farber. 

Powerful medicine in a pill 

Hartley-Brown is working to learn more about the potential for a novel drug for multiple myeloma, called mezigdomide, to reach more patients. Mezigdomide, which is not yet approved by the U.S. Food and Drug Administration and is only available in clinical trials, is an oral medication that interferes with a complex intracellular protein system (the cereblon E3 ubiquitin ligase complex) found in myeloma cells causing changes that result in killing the myeloma cells. 

Mezigdomide alters the same complex as existing drugs for myeloma, such as pomalidomide, lenalidomide, and thalidomide, but has a different underlying mechanism and is highly potent. In an early-stage clinical trial led by Dana-Farber’s Paul Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center, it has shown positive results in patients with relapsed, refractory disease. Iberdomide, also a once daily pill with a similar mechanism of action, has also shown favorable treatment benefit to patients with advanced recurrent myeloma. 

“An oral drug is much easier for community oncologists to prescribe and offer patients in rural areas or areas where patients don’t have access to an advanced healthcare system or academic cancer center,” says Hartley-Brown. 

To increase the number of people who have access to these medicines, and to ensure they are being tested on a representative population of people with multiple myeloma, Hartley-Brown is working to involve as many community cancer centers as possible in clinical trials of these agents. 

This work involves collaborations with cancer institutions nationally. It also involves deep conversations with physicians who serve diverse populations of patients with multiple myeloma to understand how patients feel about participating in clinical trials and what factors might make them more likely to do so.  

“It’s a learning process and a process of growth,” says Hartley-Brown. “When we improve the participation of BIPOC [black, indigenous, and people of color] patients in these myeloma treatment trials, it will help us be sure the treatment outcomes are applicable to a diverse population. The clinical trial patient population these medicines are evaluated in should reflect the population in the real world.” 

Outpatient clinics for CAR T-cell therapy 

Among the many advances in medicines for multiple myeloma are cell therapies, such as an immunotherapy called CAR T-cell therapy. CAR T-cell therapies involve the collection a patient’s own immune cells, engineering of those cells in the laboratory to boost their cancer fighting abilities, and re-infusion of the cells into the patient. 

CAR T-cell therapies have shown excellent results in patients with multiple myeloma, but the therapy typically involves a stay as an in-patient at a specialized center that can provide the therapy. This type of cell therapy is currently only available at large academic cancer centers, such as Dana-Farber. 

Outpatient options for CAR T-cell therapy are becoming more common – including at Dana-Farber – as doctors have learned more about how to manage the serious side effects that can occur with the treatment. However, this option still requires that the patient be nearby for an extended period. Furthermore, CAR T-cell therapy is expensive and might not be feasible for all patients. 

“CAR T is an example of a medicine on that floating shelf. It is out of reach for many people,” says Hartley-Brown. “Expanding outpatient CAR T and working on cost-effectiveness could help improve access.” 

Learn more about receiving outpatient CAR T-cell therapy at Dana-Farber. 

Outpatient clinics for bispecific antibody therapies 

Bispecific antibody therapies are medicines that are often injected under the skin into the subcutaneous fat and activate the immune system against multiple myeloma while also causing direct myeloma cell death. The drug is an antibody that connects to both myeloma cells and to T cells, bringing them closer together so that T cells be more active and attack the cancer cells. 

“Unlike CAR T-cell therapies, bispecific antibodies aren’t on as high of a floating shelf,” says Hartley-Brown. “But they are not as simple as an infused therapy or an oral medicine.” 

One complication with bispecific antibodies is that they can result in side effects that require immediate and specialized intervention. While more sites, including Dana-Farber, are offering outpatient bispecific antibody therapy, patients still must be monitored closely and be in close range of a center that has experience managing the side effects. 

Toward a medical system that serves all 

The changes required to build a health system that serves all require more inclusive research. For example, until recently, the normal ranges for infection-fighting blood cells called neutrophils only reflected normal values for a subset of the general population. 

A genetic alteration that is more common among people of African descent, called Duffy Null status, results in lower numbers of circulating neutrophils in the blood. Those lower numbers have only recently been recognized to be within the normal range.  

It is critical to adjust the normal range to include lower neutrophil counts so that patients are not inadvertently excluded from clinical trials and patients do not have treatments, such as chemotherapy, stopped prematurely.  

Adjusting these criteria, says Hartley-Brown, is an example of how the work of improving health care for all involves “a lot of meeting of the minds, discussion, and chipping away at things.” 

“We all see the need, and we are working on many fronts towards a common goal,” she says.