Areas of Consensus and Differences Among a Panel of Experts on the Optimal Use of Newly Approved Agents to Treat Multiple Myeloma (MM): Results from an Annually Updated Online Decision Support Tool

Background

In 2015, the FDA approved 5 new agents and/or combination regimens for the treatment of patients with relapsed/refractory (R/R) MM. In addition, new clinical data support using new regimens in the first-line setting. This rapid expansion of available treatment options has greatly increased the complexity of treatment decisions for patients in this disease setting. Clinical practice guidelines list multiple preferred treatment options for MM and can be challenging to apply to specific patients with a mixture of presenting features. Since 2013, we have developed and updated an MM online decision support tool designed to provide clinicians with expert guidance on optimal treatment for defined patient scenarios. An analysis of the tool over the years has shown that experts rapidly integrate new data and available agents into practice whereas many tool users do not. Here we report data from the most recent version (2016) of this tool, capturing the impact of the rapid expansion of new therapies on expert treatment recommendations.

Methods

In June 2016, a panel of 5 experts provided treatment recommendations for 688 case scenarios across 3 settings: induction, maintenance, and R/R disease. These distinct scenarios were defined by key patient and disease characteristics that the experts considered important when making treatment choices, including: eligibility for autologous stem cell transplantation, results of chromosome analysis (cytogenetics/FISH), ECOG performance status, previous therapy and response, and preexisting comorbidities. To use the tool, these patient and disease factors and the intended treatment for that specific patient were entered through drop-down menus to display the expert choices for that case. Users were then asked to indicate the impact of the expert recommendations on planned treatment.

Results

We compared expert recommendations from the 2 most recent versions of our MM tool, compiled in March 2015 and June 2016, to assess the impact of the new data and FDA approvals on treatment patterns. The experts are generally not recommending these agents as induction or maintenance therapy. Three out of 5 experts recommended carfilzomib/lenalidomide/dexamethasone as induction therapy for preexisting peripheral neuropathy (PN) and 1 expert recommended ixazomib-based regimens as induction and maintenance therapy for patients with high-risk cytogenetics and both renal insufficiency and PN. The new agents did have a substantial impact on expert recommendation in the R/R setting. In the 2016 tool, the type of previous therapy was the primary factor affecting expert selections, whereas the number of previous lines of therapy (1-3 vs >3) had minimal impact in the R/R setting. For example, in patients refractory to previous proteasome inhibitor (PI) therapy, regimens containing either elotuzumab (30%) or daratumumab (25%) were selected frequently by experts with pomalidomide-containing regimens recommended in another 40% of these specific cases. In the 2016 tool, the use of lenalidomide/dexamethasone alone without a newly approved agent was not recommended by any expert in the R/R setting, although it had been recommended by experts in 25% of R/R case scenarios in the 2015 tool. For patient scenarios refractory to previous immunomodulatory drugs and PIs, the experts recommended daratumumab-based regimens in 67.5% of the cases in the 2016 tool whereas the use of carfilzomib/pomalidomide/dexamethasone fell from 45% in 2015 to 10% of the cases in 2016. None of the experts recommended regimens with panobinostat as their preferred choice in any patient scenario in either 2015 or 2016.

Conclusions

Expert opinions regarding optimal MM therapy continue to evolve with new evidence and FDA approvals. Our data show that newly approved therapies are having a large impact on expert recommendations for specific case scenarios in the relapsed/refractory MM setting. A detailed and updated analysis of expert and user data that captures practice trends in this rapidly evolving environment will be presented.