Impact of Novel Agents on Coverage Decisions in CLL

John L. Fox, MD, MHA: The RESONATE trial provided new information on a new class of drugs: Bruton’s tyrosine kinase inhibitors for the management of patients with CLL, both in the induction phase and in relapse. RESONATE studied ibrutinib, or Imbruvica, with chlorambucil versus chlorambucil alone, very analogous to the study that was done with obinutuzumab plus chlorambucil versus chlorambucil alone. But, what was notable about the RESONATE trial is that it provided an all-oral therapy regimen for a condition that previously had been treated primarily with IV therapies. But, interestingly, the outcomes of the RESONATE trial weren’t dramatically different than what you saw with obinutuzumab plus chlorambucil. Both had hazard ratios for overall response rates or progression-free survival that were in the 80th percentile. And so, it provided another option for providers and for patients who wanted an oral therapy. I think that’s the main take home from RESONATE, that ability to provide that all-oral regimen.

The advent of oral combination therapies for the treatment of CLL provides new therapeutic regimens for both patients and providers. How will managed care companies oversee that? Will we have preferences for the cost of care? Certainly, we are concerned about the cost. Today, most health plans have guidelines that are in place, at least prior-authorization guidelines, to ensure that the drugs that are being used, or the combination therapies that are being used, are consistent or adherent to the NCCN guidelines. But, today, most health plans don’t have preferred agents in place. We don’t require one drug over another in almost any cancer type, and that would include in the CLL space. But, given the dramatic costs and the differences in cost between some of these regimens, the question is when will the straw break the camel’s back? What’s very interesting is with the advent of the CMMI, or Center for Medicare & Medicaid Innovation, and their oncology care model, will that drive providers’ behaviors in choosing different therapies? So, for example, obinutuzumab plus chlorambucil costs about $50,000 for a 24-week induction, and then you’re done. For patients who are getting Imbruvica, or ibrutinib, plus chlorambucil, that’s induction therapy plus maintenance until progression. This is a dramatic cost difference, $160,000 a year. So, while we, as a health plan today, aren’t ready to take that plunge and require one therapy over another, it’s certainly going to be imperative for physicians to consider the cost and the outcome differentials in the future, especially as they become increasingly accountable both for costs and outcomes.

So, how will ibrutinib be incorporated into the treatment pathways? It has an indication—and almost every clinical subset has an indication for the frail and elderly—for those over 70 years old, or those younger than 70 years old with complications. It has indications for those under 70, and has an indication for patients who have a high-risk p17 deletion. I think if providers wanted a drug that they could go to in almost any clinical circumstance, that certainly has the broadest number of indications. Although, I would say that there still are other therapeutic options that exist for those under age 70 who don’t have comorbidities. FCR (fludarabine/cyclophosphamide/rituximab) is still a standard of care, and is dramatically cheaper. I can’t imagine that a physician would use that, nor would we, as a health plan, allow it. I think the increasing number of studies that are available to demonstrate the efficacy of ibrutinib will certainly expand its use, and potentially as a first-line agent.