Personalized Selection of Upfront Therapy in CLL - Episode 9

Diagnostic Factors and Treatment Changes in CLL

John Fox, MD, MHA: Probably the most critical thing in establishing a treatment regimen for a patient is to understand the risk factors associated with each individual patient. As I mentioned earlier, patients who have 11q or 17p deletions and those who have complex karyotypes and the IGHV gene are at much higher risk of progression and early mortality. So, paying for those tests to understand which therapy is most appropriate for that patient is critical. Remarkably—or maybe not—the cost of that diagnostic intervention is a pittance in comparison with the cost of the therapies. So, it’s in everyone’s interest—the patients, providers, and the payers—to ensure that we understand what those risk factors are to ensure that we have the patient on the most appropriate therapy.

For example, for very low-risk patients—those under age 65 who don’t have any deletions, who have a normal karyotype, who don’t have multiple mutations and IGHV—those patients may be appropriate for FCR, or fludarabine/cyclophosphamide/Rituxan (rituximab). Whereas those who have more complex risk factors, such as multiple comorbidities and/or unmutated IGHV and 17p deletions—those patients might be more appropriate for molecularly targeted therapies, such as Imbruvica.

The evolution of the NCCN guidelines has really helped payers and providers alike identify what the optimal therapy is for a given patient. For example, in first-line treatment-naïve patients with CLL, historically, we’ve used a combination of chemotherapy and Rituxan. There now are a number of different therapies approved, including ibrutinib alone. But just as importantly, the NCCN has helped identify what the preferred regimens are and then what the alternate therapies are. So, it has gone from what I called a “13-line highway” to where you could use any of those, and they didn’t specify which were optimal, to now 2 or 3 or 4 preferred regimens in first-line treatment-naïve patients. And then, likewise in relapsed/refractory patients, first-line therapy could include ibrutinib alone or a combination of newer agents such as Zydelig (idelalisib)/rituximab or venetoclax/Rituxan.

More complicated then—or maybe less so complicated—are patients who have 17p deletions where ibrutinib is the only category 1 NCCN recommendation, followed by some of the Rituxan-containing regimens, with venetoclax or Zydelig after that.