June 9, 2016 – The Institute for Clinical and Economic Review (ICER) has released a Final Evidence Report and Meeting Summary, titled Treatment Options for Relapsed or Refractory Multiple Myeloma: Effectiveness, Value, and Value-Based Price Benchmarks. The final report, which reviews the comparative clinical effectiveness and value of treatment options for multiple myeloma, incorporates a summary of votes taken on the evidence during a public meeting of the Midwest Comparative Effectiveness Public Advisory Council, as well as key policy recommendations stemming from discussion with a panel of experts during the meeting. The Final Report and Meeting Summary is accompanied by a “Report-at-a-Glance” document, which summarizes the key points of the evidence review and economic model, as well as the voting results and policy recommendations.

ICER’s report focuses on adults with multiple myeloma whose disease has not responded to at least one previous line of treatment (i.e., refractory) or has relapsed following such treatment, are not currently on maintenance treatment, and are not being considered for stem cell transplant. A version of the report was the subject of public deliberation at the May 26, 2016 inaugural meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) in St. Louis, MO.

A key goal of ICER’s reports is to ensure that patients, providers, insurers, and policymakers have the information they need to support efforts to improve the quality and value of care.

In his introductory remarks to the proceedings in St. Louis, ICER President Steven D. Pearson, MD, MSc noted “We are all here today because we share a common vision of a future. It’s a future in which better evidence allows more personalized and tailored treatments for patients with multiple myeloma.” He also states, “We all want that, and we want it in a way that can prove sustainable for patients, for those who pay for insurance, and for broader society.”

During the public comment portion of the meeting, patients raised serious concerns about the report and how the results would be used.  Later in the meeting, as part of the policy roundtable segment, patient representative Yelak Biru noted, “I want to commend ICER for creating this forum where we can talk about cost and not just the efficacy of a particular drug or combination of drugs.” A full recording of the meeting can be found here.

Highlights of the meeting, as summarized in the Final Evidence Report, include:

Comparative Clinical Effectiveness and Value

When voting on the evidence for the clinical effectiveness of the treatment regimens under review, the Midwest CEPAC voted with near unanimity that, for both second- and third-line therapies, the addition of carfilzomib (CFZ), elotuzumab (ELO), or ixazomib (IX) to the combination of lenalidomide (LEN) and dexamethasone (DEX) provides greater net health benefit than LEN+DEX alone. However, evidence was considered inadequate to discern a difference in effect between the three combinations due to a lack of head-to-head trials and findings of network meta-analyses suggesting relatively comparable improvements in progression-free survival across treatment regimens. A majority of the Council voted that, for third-line therapy, the evidence was not adequate to demonstrate a net health benefit of adding Panobinostat (PAN) to bortezomib (BOR) and DEX, as compared to BOR+DEX alone, and that current evidence was inadequate to demonstrate a net health benefit of daratumumab (DARA) when used earlier than its FDA labeled indication for patients who have previously tried at least three different therapies.

The Council votes on the long-term care value of these treatment regimens were divided between “low” and “intermediate” value, with a majority of the Council favoring “intermediate” value for all second-line combinations (CFZ, ELO, or IX +LEN+DEX).   For third-line combinations, a majority of the Council considered ELO+LEN+DEX to be low care value, and the combination of either CFZ or IX with LEN+DEX to represent intermediate care value. Votes were evenly split between low care value and intermediate care value for the combination of PAN+BOR+DEX.

Policy Recommendations

During the meeting, the Council discussed the policy implications of their evidence votes with a panel of patient representatives, clinical experts in the field of myeloma, and those from payer and pharmacy benefit manager organizations.  Several key policy themes emerged from this discussion, which are detailed in full in the final report. Among the key recommendations are the following:

  • Insurers should avoid interpreting the lack of evidence distinguishing effectiveness among multiple myeloma therapies as a rationale for step therapy or “fail first” coverage policies. Many patients with multiple myeloma may cycle through all or most of the available treatments, and there is substantial variation in the mechanisms of action and the patient values that guide consideration of the trade-offs between extended survival and the varying side effect profiles of the available therapies.
  • The clinical research community—including researchers, funding agencies, manufacturers, and patients—should work together to design and conduct clinical research to address evidence gaps and provide the most valuable information possible about treatment choices and timing for specific patient populations
  • Patient organizations should be given a leadership role in efforts to change the way clinical trials are designed to advocate for rigorous study in real-world populations. As part of this effort, patient organizations should seek to reduce the barriers that impede high participation in clinical trials.
  • Manufacturers should consider the extension to both survival and time on treatment in the pricing strategies for new therapies, and should take the lead in designing mechanisms to discount all components of a treatment regimen, as advances in therapies for multiple myeloma often involve increasing the number of drugs a patient is taking during a treatment course. Manufacturers should also work to improve the quality of evidence available around the time of drug approval to better inform treatment decisions.
  • When clinically appropriate, clinicians should consider sequencing treatment regimens for patients by commencing treatment with the most cost-effective regimen. Risk-bearing provider groups should also identify mechanisms to manage costs across the health system to avoid too narrow a focus on drug costs within individual classes or patient populations.

The final report, along with the Report-at-a-glance, are available on the ICER website.