CLL: Managed Care Outlook on Clinical Trial Data

John Fox, MD, MHA: Recently, Kipps et al published a paper looking at an integrative analysis of 3 different studies: RESONATE, RESONATE-2, and the HELIOS trials, which looked at outcomes for high-risk patients, including the karyotype and mutations, etc. And what they found, interestingly, was that independent of those risk factors, patients did generally better on ibrutinib compared with anti-CD20 therapy plus chemotherapy. So, historically, we’ve always looked at those risk factors as prognostic, but in the Kipps paper, it didn’t appear that those factors were as important as they have been in the chemotherapy and anti-CD20 space.

So, what does that mean to payers? From our vantage point, it simply means that patients do generally well independent of those risk factors. And for providers and patients, that can be very important, too—knowing that they’ll have a generally good response independent of what we’ve historically considered as negative risk factors.

Recently, O’Brien published a paper looking at 5-year outcomes in patients who were initially studied with ibrutinib in their phase Ib and phase II trials. It was very interesting, because patients accumulated a complete response over time—29% of patients who were treatment-naïve achieved a complete response over time, whereas 10% of patients who had a relapse and were treated in the relapsed/refractory setting also had complete response over time.

It was also notable that patients who were treated in earlier lines of therapy, especially treatment-naïve, did much better than those patients who were treated as later second-, third-, or fourth-line treatment. Patients who had a complex karyotype did less well, especially if they were treated later. And then, finally, most of these patients were able to tolerate that therapy over 5 years. O’Brien reported that 65% of patients who started therapy were able to continue that through 5 years in the treatment-naïve setting, whereas 30% of patients in the relapsed/refractory setting were able to continue on therapy. So, although there are some toxicities associated with ibrutinib, including the onset of atrial fibrillation, most of these patients tolerated therapy very well.