Multiple Myeloma Continues to Pose Management Challenges for Payers

Multiple myeloma, an incurable blood disease that starts in the bone marrow and can be a relatively rare cancer, has an array of products available to treat it, and new agents — including the first gene therapy for the disease — continue to gain FDA approval. However, as the therapies are different types of drugs, management of the space can be challenging.

Winston Wong, Pharm.D., president of W-Squared Group, points out that about 20 therapies are available to treat multiple myeloma. As of April, the National Institutes of Health listed more than 200 clinical trials, many for gene therapies, he adds. “Thus, the already crowded and complicated field of treatment options is only going to get more crowded,” he tells AIS Health, a division of MMIT.

“The evolution of multiple myeloma treatments reflects our greater understanding of the various pathways that mediate the disease,” he explains. “While induction regimens have remained rather consistent over the years, the majority of the recently approved treatment options are in the maintenance and resistant/relapsing stages of treatment.”

According to Mesfin Tegenu, CEO and chairman of RxParadigm, Inc., the evolution in treatments over the past couple of decades has extended “median patient survival by three-fold to about 10 years. This has been in large part because of our understanding of the disease and the ongoing clinical studies that have aided in discovering new targeted therapies. However, a patient’s genetic complexity, variability and tumor progression, as well as the rise in cases over the years, continue to showcase the ongoing need for novel therapies.”

“The recently approved treatment options pretty much have their niche populations defined within the approved indication, indicating first-line through fifth-line treatments,” says Wong. “The newer agents are becoming more defined as to when the medication is approved for as it pertains to stages of the disease, as well as after which lines of therapy. Therefore, payers will usually manage to the approved indication, even if they have an aggressive clinical pathway program in place.”

Managing the disease is a challenge to payers, Tegenu says, “from the varying options for treatment based on patient risk stratification to therapies covered under the medical vs. pharmacy benefits that are used in treatment of multiple myeloma. While every patient treatment may vary, standard triple therapy treatment continues to be a combination of immunomodulatory drugs, proteasome inhibitors and anti-CD38 antibodies. One standard induction therapy option is RVd (lenalidomide, bortezomib, dexamethasone) based on its effectiveness and improvements in overall survival. Preferred therapies will be based on risk stratification of disease by eligibility for HCT [i.e., hematopoietic cell transplantation], genetics and patient comorbidities.”

As payers struggle to control costs for multiple myeloma, “contracting with specialty pharmacies will play a significant role in cost containment,” asserts Tegenu. “Meanwhile, drugs that pay under the medical benefit will need to be appropriately managed.”

Patients often are treated with a combination of therapies, which has “added to the complexity of managing this disease,” he says. The National Comprehensive Cancer Network bases its preferred initial treatment regimens on whether people are eligible for a transplant, whether they have been treated before and whether they need maintenance therapy. “Additionally, they offer many other regimen options to choose from, which has required payers to comb through clinical trial data and studies to thoroughly evaluate the results and determine how the disease should be managed.

“With triple drug regimen being the mainstay of initial treatment and ongoing rise of variability in therapeutic options currently and in development, cost will inherently rise,” he continues. “Therefore, payers will need to consider the costs of different treatment options but also their ability to improve overall survival.”

“The current multiple myeloma drugs fall into various drug classes, including proteasome inhibitors, immunomodulatory drugs, alkylating agents, corticosteroids, histone deacetylase inhibitors, bisphosphonates and monoclonal antibodies,” explains Wong. “Looking at the approved indications, there is not much overlap. We are also dealing with a condition where refractory and relapse is common. There is not a strong KOL [i.e., key opinion leader] consensus as to the sequence of medications that should be used for treatment. Treatment selection is largely based upon the patient’s clinical presentation, the financial/logistical desires of the patient and then lastly, the experience of the treating oncologist. All of these factors make standardizing treatment sequences by payers difficult.”

Therefore, he says, “management is limited to identifying the appropriate patient population for any particular medication that is consistent with the approved indication. Medication differentiation is only at the highest therapeutic class level.”

Payer management of multiple myeloma also needs to include its potential comorbidities. Wong points out that “there is increasing evidence of serious cardiovascular side effects associated with the proteasome inhibitors and immunomodulatory drugs in patients with underlying cardiovascular risk factors or disease. Cardiotoxicities include cardiomyopathy, heart failure, hypertension, arrhythmias and thromboembolism.”

And because the incidence of multiple myeloma increases with age, occurring mostly among people in their late sixties and early seventies, “it is common to see comorbid conditions such as neuropathy, infection risk, anemia, VTE [i.e., venous thromboembolism] and renal failure that may impact the management of the disease, from HCT eligibility to treatment regimens,” adds Tegenu.

The FDA has approved two new treatments — including the first chimeric antigen receptor T-cell (CAR-T) therapy for multiple myeloma — and an additional indication for a third since late February.

On Feb. 26, the FDA granted accelerated approval to Oncopeptides AB’s Pepaxto (melphalan flufenamide) with dexamethasone for adults with relapsed or refractory multiple myeloma who have received at least four lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent and one CD38-directed monoclonal antibody. It is the first FDA-approved anticancer peptide-drug conjugate.

FDA Approved First CAR-T for Condition

On March 26, the FDA approved Bristol Myers Squibb and bluebird bio, Inc.’s Abecma (idecabtagene vicleucel) for the same use. It is a B-cell maturation antigen (BCMA)-directed therapy and the first CAR-T agent in the class. The price for the one-time dose is $419,500.

On March 31, the FDA gave Sanofi’s Sarclisa (isatuximab-irfc) a second indication in combination with carfilzomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. The therapy already had approval in combination with pomalidomide and dexamethasone for adults with relapsed or refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

Abecma’s approval is significant, sources tell AIS Health. “CAR-T therapies are considered standard of care for certain hematological malignancies as a result of their specificity to each patient’s immune system,” says Tegenu. “While longer follow-up data will be needed, Abecma will continue to trail behind other therapeutic options during the course of disease treatment, as its use will be dependent on the progression of a patient’s disease, resistance to multiple alternative therapies and access. In those patients who no longer are receiving high response rates from standard treatment regimens, Abecma will help to extend their survival further. Initial studies have shown significant length of remission for these previously relapsed patients.”

“The significance of Abecma as the first CAR-T for multiple myeloma is high,” maintains Wong. “It represents the first use of successful gene therapy technology in multiple myeloma, representing a 72% overall response rate, with a 28% complete response, of which 65% of the CR remained in CR for at least 12 months. Clinical outcomes of this magnitude have not been seen with any other therapy in the relapsed/refractory stage. Of note is that Abecma is the first, but not the last, gene therapy product, as many other gene therapies are in the pipeline.”

The next such product to potentially receive FDA approval is Johnson & Johnson and Legend Biotech Corp.’s ciltacabtagene autoleucel (cilta-cel), also a BCMA-directed antibody, which could be approved in the second half of this year.

“Current treatments available may result in remission, [but] these patients continue to relapse, and there’s currently no cure,” said Lynn Nishida, R.Ph., chief pharmacy officer and managing partner at Trend HealthCare Partners, during a Feb. 11 webinar. “Both CAR-T products by Bristol and J&J aim to address these patients who have gone through multiple treatment options. The results in their clinical trials are really intriguing as well.” Long-term follow-up data from cilta-cel showed a 100% overall response rate and an 86% CR at a median of 11.5 months, she said.

“The key to the success of these products will be how long of a duration that they can keep someone in remission and their complete response, as well as the side-effect profile,” said Nishida, which includes cytokine-release syndrome and neurotoxicity events. However, she noted, patients can be closely monitored and managed appropriately.

Nishida said that Abecma initially will compete with GlaxoSmithKline’s Blenrep (belantamab mafodotin-blmf), the first BCMA-directed antibody in multiple myeloma. The FDA gave it accelerated approval on Aug. 5, 2020, for the treatment of adults with relapsed or refractory multiple myeloma after at least four lines of therapy, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. Dosing is weight-based, and based on an average weight of 175 pounds, its monthly cost is around $24,000.

Tegenu also expects competition from the emerging class of bispecific T-cell engagers (BiTEs), which have “a different mechanism of action that does not pose the challenges of requiring individualized cell-based therapies. The ease of manufacturing an ‘off-the-shelf’ access potentially increases the availability of these agents to a larger patient population. However, these therapies have a short half-life and require infusion over a period of time.”

In May, the Institute for Clinical and Economic Review (ICER) released a Final Evidence Report on Abecma, Blenrep and cilta-cel that found the first two drugs were low long-term value at their current prices.

ICER President Steven Pearson, M.D., said in a statement that while “these three new therapies with new mechanisms of action represent a very important expansion of the clinical options available to patients and oncologists,…manufacturers should restrain their pricing and work with payers to ensure that payment mechanisms and overall benefit coverage can help patients from all walks of life get affordable access to these treatments.”

“The treatment landscape for multiple myeloma has evolved quite rapidly over the years, as it historically focused on palliative care to now highly intensive triple- to even quadruple-based treatment regimens that have significantly prolonged the duration of remission and overall survival,” says Tegenu. “Treatment options for multiple myeloma are complex, ranging from variations in combination of therapy to route of administration,” including intravenous, subcutaneous and oral choices. “Current therapy options do not offer the same route of administration for all drugs. Now with the introduction of T-cell and bispecific T-cell engagers, it will be interesting to see how payers will manage these high price-tagged therapies.”

Contact Nishida at, Tegenu at and Wong at

This story was reprinted from AIS Health’s monthly publication RADAR on Specialty Pharmacy.

© 2024 MMIT
Angela Maas

Angela Maas

Angela has an extensive background of editing, reporting and writing for trade and consumer publications. She has written Radar on Specialty Pharmacy (formerly called Specialty Pharmacy News) since she joined AIS Health in 2005 and has broad knowledge of the various issues at play within the space. Before joining AIS Health, she was managing editor at Employee Benefit News and Employee Benefit News Canada and managing editor at HemAware (a hemophilia publication), Lupus Living and Momentum (a multiple sclerosis publication). She has a B.A. in English and an M.A. in British literature from Arizona State University.

Related Posts

April 18

Medicare-Negotiated Drugs May Not Get Favorable Coverage In Part D: Will CMS Intervene?

Read More
April 18

Older Drug Gets New Indication for Use in Aggressive Cancer

Read More
April 18

Budgets Propose Eliminating Interchangeability Status for Biosimilars

Read More


Sign up for publications to get unmatched business intelligence delivered to your inbox.

subscribe today