Role of Real-World Data and Sequencing in CLL

John Fox, MD, MHA: As payers, we’ve historically used randomized clinical trials to help inform our coverage decisions. But frankly, at least in many states—and over half the states—there are FDA mandates to cover FDA-approved cancer drugs, even for non—FDA-approved indications. Most health plans have also said that we’re going to follow the NCCN guidelines in making our coverage decisions. So, randomized clinical trials from the basis of the NCCN guidelines and from the basis of the FDA approval—how do we use real-world data? Interestingly, in the CLL space, there have been real-world data that show that patients on maximum doses of ibrutinib can be weaned off those high doses and potentially reduce the risk(s) of development of resistance and, at the very least, reduce the toxicities associated with the drug without any impact on progression-free survival. So, that’s the kind of real-world evidence that will help us understand when we can wean the dose or maybe even stop the dosages of medications.

With the plethora of treatment options, from chemotherapy alone to chemotherapy with anti-CD20 therapies to the advent of PI3K, BTK, BCR-2 therapies, the question is, how do you sequence these things? Frankly, we just don’t have enough data to help us understand how these should be sequenced. And because of that, that’s really left to the provider and perhaps NCCN, to help decide what the proper sequencing is. One of the challenges is that although ibrutinib may be first-line therapy for treatment-naïve and relapsed remitted patients, the key question is, once you’ve relapsed on ibrutinib, where do go next?

There are a number of different treatment options, and we’re going to have to rely on clinical trials to help us decide which therapies are optimal in that setting. But I would say at this point, we’re really leaving it to the physician and the experts to decide how to best sequence. Some of that may be determined by the risk factors that patients have. FCR may be just fine for low-risk patients under age 65 without comorbidities, but, again, that’ll be something that the physician and patient have to decide.

The advent of OCM, or the Oncology Care Model, through CMMI has changed the dynamics a little bit in the fact that now providers are also acting as payers; they’re under a fixed budget, or an episode payment. So, it will be interesting to see how providers sequence therapies, especially if they’re at risk, and they have the choice between a regimen that may cost $50,000 a year and one that costs $150,000 or $200,000 a year. So, that’s going to change the dynamics significantly. And where that goes, we’ll have to wait and see.