Multiple Myeloma Treatment: The Price of Success

Editor's note: This is expanded version of an article that was posted as part of coverage of the 2025AMCP Annual Meeting.

The treatment of multiple myeloma is often described as complicated or complex. The description is apt and reflects the fact that the treatment of this cancer of plasma cells is one of contemporary oncology’s success stories. The complexity comes from the wealth of highly effective multidrug regimens that have gained FDA approval in a relatively short amount of time and the many lines of therapy. Adding even more complexity to the picture is the still limited amount of data available on the optimal sequences for the many drugs. The labyrinth of clinical issues also has daunting financial dimensions to it. Many of the new multiple myeloma agents have five- and six-figure price tags. The total cost of treating someone with multiple myeloma over the course of their illness can easily climb into the millions of dollars.

Laura R. Bobolts, Pharm.D.

At an educational session on multiple myeloma at the Academy of Managed Care Pharmacy (AMCP) annual meeting in April in Houston, Laura R. Bobolts, Pharm.D., said that there are 12 primary treatments for patients with multiple myeloma who are eligible for stem cell transplant, which involves replacing diseased stem cells in the bone marrow with healthy ones, and 10 for those who are not eligible for such transplants. For patients whose disease is classified as relapsed/refractory after one to three prior therapies, the armamentarium expands to 50 drugs.

“It’s fantastic for patients, but it just shows how complex it is because if you pick one of those 50, then which of the 50 do you pick next?” said Bobolts, senior vice president, clinical strategy and growth at OncoHealth, a digital healthcare company for patients with cancer. “That’s really a challenge for us to make sure that patients are receiving the best treatment.”

Top 3 in ‘spend’

Multiple myeloma is a cancer of blood plasma cells that typically affects older people; the median age of those who are diagnosed is 69. Multiple myeloma is classically identified by elevated calcium levels in the blood, renal failure, anemia and lytic bone lesions — CRAB features, for short. It typically begins as a premalignant disease, which is usually asymptomatic, known as monoclonal gammopathy of undetermined significance. From there, it may progress to what is commonly known as smoldering multiple myeloma, which is also asymptomatic but represents a more advanced form of the premalignant disease. This stage then progresses further to active symptomatic multiple myeloma.

According to the American Cancer Society’s “Cancer Facts and Figures 2025” report, there will be approximately 36,000 new cases of multiple myeloma diagnosed this year and slightly more than 12,000 deaths related to the disease. It is the 14th most common cancer, representing 1.8% of new cancers in the U.S., according to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data. Even so, it is among the top three cancers as far as payer expenditures are concerned, noted Bobolts, a ranking that is the direct result of the plethora of therapies and their prices.

The pace of innovation has increased substantially in recent years. In July 2024, the FDA approved a combination of Darzalex Faspro (daratumumab and hyaluronidase) with Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone for patients who are eligible for stem cell transplant. Two months later, the drug regulators gave the green light to Sarclisa (isatuximab) in combination with the same three agents for patients who are not eligible for a stem cell transplant. Both Darzalex Faspro and Sarclisa target the CD38 protein on the surface of multiple myeloma cells. The FDA also approved Abecma (idecabtagene vicleucel), a second chimeric antigen receptor T cell (CAR-T) treatment for multiple myeloma, last year.

The flurry of new drugs has made multiple myeloma an expensive disease for payers. Medicare expenditures on multiple myeloma therapy increased from $2.55 per member per month (PMPM) in 2018 to $5.20 PMPM in 2023, Bobolts told the AMCP audience. The drugs most responsible for the expense are the CAR-T therapies, which include Carvykti (ciltacabtagene autoleucel) as well as Abecma and the bispecific antibody therapies Tecvayli (teclistamab), Elrexfio (elranatamab) and Talvey (talquetamab), according to Bobolts

“The economic impact of multiple myeloma is significant because the costs are so high,” said Bobolts. “This puts a burden on our patients. We really need to do a better job of finding solutions to help our patients, whether it’s using financial navigators or different care management tools to get the patients to the right resources to help make sure that they can pay for these medications.”

The new drugs have helped people with multiple myeloma live longer, so what was once an unsparing, lethal disease has begun to resemble a chronic condition that is managed with multiple drugs. SEER data now show that the median overall survival for multiple myeloma is 8.6 years, Bobolts noted, and that the death rate has dropped by 56% over the past 25 years. As a result, there are now approximately 180,000 people in the U.S. living with multiple myeloma, according to SEER data.

The longer survival times have also led to patients staying on their treatments for longer. Additionally, the treatment regimens that used to depend on one drug now consist of three or four, such as the combinations that include Darzalex Faspro and Sarclisa. With this shift, spending on long-used drugs has skyrocketed. Data from a study published in the journal Blood in 2023 showed that annual Medicare spend for multiple myeloma increased from $2 billion for 14 common therapies in 2013 to $10.2 billion in 2021. Findings reported in the journal Oncology and Therapy in 2022 showed that the total healthcare cost to treat patients with multiple myeloma who had received four or more lines of therapy was just over $750,000 over a 21-month period.

Treatment trends

One of the current trends in multiple myeloma treatment is treatment when the disease is asymptomatic, particularly for those with smoldering multiple myeloma. Although this new paradigm offers hope for patients, it represents a fresh set of challenges for treatment sequencing. In many scenarios, this treatment delivered for smoldering multiple myeloma is best guided by risk, although the exact criterion for assessing risk remains somewhat unclear. Additionally, the assessment of quality-of-life measures following treatment of smoldering multiple myeloma has largely been unexplored, Susan Wojcicki, Pharm.D., clinical strategy pharmacy lead at Humana, said at the AMCP meeting.

Susan Wojcicki, Pharm.D.

“Consideration for the treatment of high-risk smoldering myeloma should be individualized. Every patient should be considered separately. The risk versus the benefits should be considered, and there should be a conversation with those who are afflicted with this disease,” said Wojcicki. “This should include the treatment risk with the therapies and quality of life considerations. The question we need to continue to ask ourselves in oncology and hematology is whether this is overtreatment or undertreatment.”

Active monitoring is still broadly used for those with lower-risk smoldering multiple myeloma. Consideration of active therapy begins as patients move into the intermediate and high-risk categories. Studies have assessed Revlimid and Darzalex (daratumumab) in these scenarios. The most recent data for this approach came from the AQUILA study, which showed an improvement in survival and a delay in multiple myeloma progression with Darzalex.

For those in the low-risk group, a clinical trial is a viable prospect, Wojcicki noted. She added that National Comprehensive Cancer Network guidelines recommend a clinical trial as a preferred option for those with high-risk smoldering multiple myeloma. For patients with full-fledged active multiple myeloma, the frontline regimen of choice has become quadruplet therapy, which is Darzalex or Sarclisa added to triplet therapy, which consists of a proteasome inhibitor, such as Velcade, Kyprolis (carfilzomib) or Ninlaro (ixazomib); an immunomodulatory agent, such as Revlimid or Pomalyst (pomalidomide); and a corticosteroid. Following this “induction therapy, patients are then considered for stem cell transplant, followed by a maintenance treatment period. Some patients are even considered for two stem cell transplants, Bobolts noted.

How clinicians and researchers measure the response to the growing array of treatments is also changing. Using very sensitive polymerase chain reaction, flow cytometry or next-generation sequencing techniques, they look for minute numbers of myeloma cells in the bone marrow. These tests can establish whether there is minimal residual disease (MRD) by detecting just one cancer cell amid 10,000 to 100,000 normal cells. Some researchers want to use MRD to assess the efficacy of drugs in clinical trials. Last year, the FDA’s Oncologic Drugs Advisory Committee voted unanimously in favor of using MRD as a surrogate end point in accelerated approvals of multiple myeloma drugs.

“MRD status is going to transform how we understand this disease, how we treat this disease, how we bring drugs to market,” said Wojcicki. “Monitoring MRD is integral to understanding the treatment efficacy and optimizing future therapeutic strategy.”

In the relapsed/refractory setting, CAR-T has been moving its way into the earlier lines of therapy, Wojcicki noted. It was initially approved following four or more prior lines of therapy but is now indicated in some cases following just one prior line of therapy.

The bispecific antibody therapies are a relatively new development. They are now approved for later treatment, following four or more prior lines of therapy. Tecvayli and Elrexfio attach to the B-cell maturation antigen (BCMA) on the tumor cell and the CD3 protein complex on the T cell to help elicit an immune response. Talvey works a little differently, attaching to the GPRC5D protein on the tumor cell and CD3 on the T cell.

Melissa Pozotrigo, Pharm.D.

As is typically the case with multiple myeloma treatment research, scientists are studying new combinations. Investigators conducting the RedirecTT-1 study are exploring the combination of Tecvayli and Talvey for patients with relapsed/refractory multiple myeloma, noted Melissa Pozotrigo, Pharm.D., a senior clinical oncology pharmacist at OncoHealth, who was on the AMCP panel with her colleague Bobolts and Wojcicki. Early results from a study of that combination reported in the New England Journal of Medicine in January 2025 showed promise. Pozotrigo commented on the formidable cost. “This combination of therapy will be very interesting from a cost perspective. It will be interesting to see how this affects the treatment paradigm because these are two costly agents,” she said.

Another study is looking at Tecvayli at a fixed duration, with continuation of therapy based on response criteria. In the LimiTec study, those with a very good partial response or better after six to nine months will have the option to continue therapy in favor of active monitoring for up to 24 months. MRD will also be assessed as part of this study.

More choices

The multiple myeloma treatment decision trees may soon bristle with more branches, with two additional therapies awaiting FDA approval this summer. The first is the possible reintroduction of Blenrep (belantamab mafodotin), which was pulled from the market in 2022. GSK announced in November 2024 that the FDA had accepted its application for Blenrep in combination with other drugs (Velcade, Pomalyst) and is scheduled to make a decision in July 2025. Development of another agent, Regeneron’s linvoseltamab, a CD3/BCMA bispecific antibody, hit a snag with a complete response letter from the FDA. With manufacturing issues potentially addressed, Regeneron issued a news release in February 2025, saying a decision is expected in July 2025.

“Off-the-shelf” CAR-T is one of the frontiers of multiple myeloma treatment. Abecma and Carvykti require collecting T cells from the patient, shipment to an off-site manufacturing facility, genetic engineering of those T cells, shipment back, and then infusion, an expensive, bespoke process that can take up to four weeks, explained Pozotrigo. In contrast, off-the-shelf, or allogeneic, CAR-T involves using T cells from donors that would be stored and ready for use. Theoretically, off-the-shelf CAR-T would speed up treatment and perhaps be less costly.

Pozotrigo mentioned two off-the-shelf CAR-T treatments in development, ALLO-715 and P-BCMA-ALLO1. “We have to see that the data looks really mature,” she said. “I think it does offer an exciting possibility for patients who are not able to wait for the products. They would now be able to have something off the shelf. I think this is very exciting and has the potential to benefit a huge subset of patients.”

Peter Wehrwein contributed reporting.