ICER Publishes Final Evidence Report and Policy Recommendations on Therapies for Multiple Myeloma

— Independent appraisal committee unanimously determined the evidence is adequate to demonstrate that CAR-T treatments ide-cel and cilta-cel both provide a net health benefit when compared to usual care; despite these benefits, for ide-cel, the only CAR-T agent having received FDA approval at this time, a majority of panelists voted that it represents "low" long-term value for money at current pricing—

— For belantamab, the majority of the committee found the evidence was not adequate to demonstrate a net health benefit, and the committee unanimously voted that belantamab's long-term value for money is "low" at current pricing —

— Policy recommendations address pricing and coverage issues while highlighting the need for all stakeholders to commit to actions that will ensure that these and other important new treatments for multiple myeloma are introduced in a way that will reduce health inequities —

BOSTON, May 11, 2021 - The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of three new treatments targeting the B-cell maturation antigen (BCMA) for heavily pre-treated patients with triple class refractory multiple myeloma (TCRMM) who have cycled through numerous previous lines of therapy:

  • idecabtagene vicleucel ("ide-cel," Abecma®, Bristol-Myers Squibb and bluebird bio), a chimeric antigen receptor (CAR) T-cell therapy that the FDA approved in March 2021 to treat TCRMM patients after four or more prior lines of therapy;
  • ciltacabtagene autoleucel ("cilta-cel," Janssen and Legend Biotech), an investigational CAR T-cell therapy for which a rolling biologic license application (BLA) seeking approval for the treatment of adults with relapsed and refractory multiple myeloma was completed in the first quarter of 2021;
  • belantamab mafodotin-blmf ("belantamab," Blenrep™, GlaxoSmithKline), which the FDA approved in August 2020 to treat TCRMM patients after four or more prior lines of therapy.

"Many people with multiple myeloma develop resistance to existing treatments, so these three new therapies with new mechanisms of action represent a very important expansion of the clinical options available to patients and oncologists," said Steven D. Pearson, MD, MSc, ICER's President. "Data are extremely limited at this time for the two CAR-Ts, and important evidence gaps remain to be filled, but having a new innovative approach become available for patients with multiple myeloma is something to celebrate.  Shadowing these new treatments are concerns that the pricing for the first approved CAR-T agent in multiple myeloma exceeds a reasonable level for its given benefit.  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.

"Belantamab appears to deliver more modest overall clinical benefit, but clinical experts believe it too will have a role in therapy.  At its current pricing, belantamab appears to meet commonly cited thresholds for cost-effectiveness, but our independent appraisal committee determined that its long-term value for money was 'low' due to questions about the magnitude of overall survival benefit and certain favorable assumptions within the economic model."

ICER's report on these therapies was reviewed at the April 2021 public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), one of ICER's three independent evidence appraisal committees.

Voting on Clinical Effectiveness and Contextual Considerations

During the public meeting, the Midwest CEPAC panelists voted unanimously (15-0) that the evidence is adequate to demonstrate that ide-cel provides a net health benefit over usual care. A majority (13-2) found the evidence adequate to demonstrate cilta-cel provides a net health benefit over usual care. Finally, a majority (10-5) found the evidence was not adequate to demonstrate a net health benefit of belantamab over usual care.

The panel also voted unanimously (15-0) that the evidence was not adequate to demonstrate a net health benefit of ide-cel compared to cilta-cel.

During their deliberations, panel members also weighed the therapies' other potential benefits, disadvantages, and contextual considerations. For both treatments, voting highlighted the following as particularly important for payers and other policymakers to note:

  • The acuity of need for treatment based on the severity of the condition being treated;
  • The patients' ability to achieve major life goals related to education, work, or family life;
  • The caregivers' quality of life and/or ability to achieve major life goals related to education, work, or family life; and
  • The patients' ability to manage and sustain treatment given the complexity of regimen.

Voting on Long-Term Value for Money

After reviewing the clinical evidence and considering the treatments' other potential benefits, disadvantages, and contextual considerations noted above, the Midwest CEPAC evaluated the long-term value for these treatments.

A majority of panelists found that ide-cel represents "low" long-term value for money. ICER's recommended health-benefit price benchmark (HBPB) range for ide-cel is $206,000-$265,000 when based on the equal value of life years gained (evLYG), and $192,000-$245,000 when based on the quality-adjusted life year (QALY), pricing levels that would require a 37-54% discount off the treatment's recently announced wholesale acquisition cost (WAC) of $419,500. ICER's HBPB calculations assume that there would be a second charge for individuals requiring retreatment, as was seen in the pivotal trial for ide-cel; if a different pricing model were to be adopted, ICER's HBPBs for ide-cel would change.

ICER did not conduct a long-term value for money vote for cilta-cel because there is no announced price for the therapy. ICER's HBPBs for cilta-cel are $350,000-$475,000 (evLYG) and $317,000-$427,000 (QALY), with the assumption that a second dose will require payment. The results for cilta-cel should be considered highly uncertain, as the evidence base is limited and much of it unpublished.

A majority of panelists found that belantamab represents "low" long-term value for money. ICER's HBPBs for belantamab are $8,400-$9,500 (evLYG) and $8,300-$9,300 (QALY) per vial, which would require no discount off the therapy's WAC of $8,277 per vial. The cost-effectiveness results for belantamab are relatively favorable due in part to patients discontinuing therapy because of side effects, as well as the high prices for the three-drug alternatives.

ICER's HBPBs are price ranges suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

Access and Affordability Alert

ICER is issuing an Access and Affordability Alert for both ide-cel and cilta-cel. Approximately 43% (ide-cel) and 50% (cilta-cel) of eligible triple- or quad-refractory multiple myeloma patients could be treated within five years before crossing the ICER potential budget impact threshold of $819 million per year. Testimony from clinical experts at the public meeting suggested that the ideal clinical uptake of the CAR-Ts would include the chance for nearly every eligible patient to receive one or the other. Given that efforts to reach this clinical target would create a short-term potential budget impact that exceeds ICER's threshold, ICER is issuing an access and affordability alert for ide-cel and cilta-cel.

The purpose of an ICER access and affordability alert is to signal to stakeholders and policy makers that the amount of added health care costs associated with a new service may be difficult for the health system to absorb over the short term without displacing other needed services, creating pressure on payers to sharply restrict access, or causing rapid growth in health care insurance costs that would threaten sustainable access to high-value care for all patients.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, and representatives from US payers and relevant pharmaceutical companies — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

  • All stakeholders have a responsibility and an important role to play in ensuring that effective new treatment options for patients with multiple myeloma are introduced in a way that will help reduce health inequities.
  • Manufacturers should seek to set prices that will foster affordability and good access for all patients by aligning prices with the patient-centered therapeutic value of their treatments.  In the setting of these new interventions for multiple myeloma, while there is considerable hope associated with the promise of the therapies, there also remains substantial uncertainty regarding their longer-term safety and effectiveness, and the platform on which they are based has been funded in part with taxpayer money.  Manufacturer pricing should also reflect these considerations in moderating launch pricing.
  • The clinical research community should move rapidly to address key gaps in evidence for treatments for multiple myeloma.  These gaps include whether patients can stop therapy while in response, how well the clinical trial populations reflect the target populations for treatment, data on preferences and patient-reported outcomes in historically disadvantaged populations, and the clinical characteristics of the disease and its affected populations that may be predictive of response.

ICER's detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER's reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER's reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER's reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER's website.

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