Multiple Myeloma Treatment Is a Success Story. The Price Is Complex Treatment Decisions — and High Costs | AMCP Annual 2025

The most used words to describe the treatment paradigm for patients with multiple myeloma were complicated and complex, according to a poll during a session on managing multiple myeloma at the annual meeting of the Academy of Managed Care Pharmacy (AMCP) in Houston.

The complexity comes from a wealth of highly effective, multidrug regimens that have gained FDA approval in a relatively short amount of time. Insinuating further complexity into labyrinth of clinical choices is the relatively limited amount of data available on the optimal sequences for these drugs. The criteria for who is eligible for a stem cell transplant also remains up to debate. On top of the clinical issues are layers of financial ones because many of the new multiple myeloma agents have five- and six-figure price tags.

Laura R. Bobolts, Pharm.D.

When turning to the National Comprehensive Cancer Network (NCCN) guidelines, there is still uncertainty noted one of the panelist at the session, Laura R. Bobolts, Pharm.D. By her count, there were 12 primary treatments available for transplant-ineligible disease and 10 for the transplant-eligible. In the relapsed/refractory setting after one to three prior therapies, the number of available therapies jumps to 50.

"It's fantastic for patients, but it just shows how complex it is, because if you pick one of those 50, then which other one 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."

The other panelists at the education session were Melissa Pozotrigo, Pharm.D., a colleague of Bobolts’ at OncoHealth and Susan Wojcicki, Pharm.D., clinical pharmacy lead at Humana.

Complex disease = complex treatment

Bobolts provided an overview of multiple myeloma, noting it is a cancer of the plasma cells that typically impacts the elderly, with a median age of 69 years at diagnosis. Multiple myeloma is classically identified using calcium elevation, renal failure, anemia and lytic bone lesions — CRAB features, for short — that are hallmarks of the damage caused by the malignant cells in the bone marrow, Bobolts noted.

Multiple myeloma begins as a premalignant disease, which is also typically asymptomatic, known as monoclonal gammopathy of undetermined significance (MGUS). 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, there will be approximately 36,000 new cases of multiple myeloma diagnosed in 2025 and slightly more than 12,000 deaths related to the disease. Despite being the 14th most common cancer, representing 1.8% of new cancers in the United States, according to the National Cancer Institute Surveillance, Epidemiology, and End Result (SEER) data, it sits in the top three for payer spend, Bobolts noted, reflecting the high cost of treatment for the disease — and its success as more lines of treatment have opened up and with patients living longer to receive them.

The pace of innovation has increased substantially in recent years, with several new therapies gaining approvals. The frontline treatment paradigm has shifted toward combinations containing several novel agents. With this transition, the cost of care has also increased, Bobolts said.

The Medicare spend 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 FDA-approved CAR-T therapies, which include Abecma (idecabtagene vicleucel) and Carvykti (ciltacabtagene autoleucel), and the bispecific antibody therapies, Tecvayli (teclistamab), Elrexfio (elranatamab) and Talvey (talquetamab) according to Bobolts

"The economic impact of multiple myeloma is significant, because of 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 five-year survival rate for multiple myeloma has steadily increased

Source: National Cancer Institute SEER data

As these treatments for multiple myeloma have improved, the long-term survival rate continues to climb making the disease begin to resemble a chronic condition. SEER data now the median overall survival for multiple myeloma at 8.6 years, Bobolts noted, with the death rate dropping by 56% in 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 treatments that were once single agents are now being deployed in regimens of four. With this shift, spending on 14 long-used drugs has skyrocketed. Data in study published in the journal Blood in 2023showed that annual Medicare spend for multiple myeloma increased from $2 billion for 14 common therapies in 2013 to $10.2 billion in 2021.

Treatment trends

One of the current trends in multiple myeloma treatment is treatment when the disease of 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 in smoldering multiple myeloma has largely been unexplored, noted Humana’s Wojcicki.

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 that 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 settings. Studies have assessed Revlimid (lenalidomide) 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 category, a clinical trial is a viable prospect, Wojcicki noted. She added that NCCN guidelines also still recommend a clinical trial as a preferred option for those with high-risk smoldering multiple myeloma.

When moving into those with active multiple myeloma, the frontline regimen of choice has quickly become so-called quadruplet therapy, which consist of an anti-CD38 monoclonal antibody add to the standard “triplet” treatment: a proteasome inhibitor, an immunomodulatory agent and corticosteroid. Following this induction therapy, patients are then considered for transplant and a maintenance treatment period. This can repeat, with many even being considered now for two stem cell transplants, Bobolts noted.

The use of minimal residual disease (MRD) has also gained in popularity as a way of risk-adapting therapy. MRD is the measurement of microscopic remnants of disease following treatment. The use of this marker remains in the early phases but was recently validated as a surrogate end point by the FDA's Oncologic Drugs Advisory Committee.

"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 earlier lines of therapy, she 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.

Bispecific antibody therapies, which attack tumor cells by attaching immune cells to tumor cells that then spur an attack the tumor cell, are a relative new addition to the multiple myeloma armamentarium. They are now approved for later treatment, following four or more prior lines of therapy. Tecvayli and Elrexfio attach to the B-cell maturationantigen (BCMA) on the tumor cell and the cluster of differentiation 3 (CD3) protein complex on the T cell to help elicit an immune response. Talvey works a little differently, attaching to the anti–G protein–coupled receptor family C group 5 member D GPRC5D on the tumor cell and CD3 on T cells.

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, for example, are exploring the combination of teclistamab and talquetamab for patients with relapsed/refractory multiple myeloma, noted Pozotrigo. Early results from a study of that combination reported in the New England Journal of Medicine in January 2025 showed promise. Pozotrigo noted 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 teclistamab 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 belantamab, which was pulled from the market. Subsequent data showed utility for the agent in combination settings. Development of the other 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 approval 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 which can take up to four weeks, explained Pozotrigo. In contrast, off-the-shelf, or allogenic, 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 in development, code named ALLO-715 and P-BCMA-ALLO1. "We have to see that data looks really matures," 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."