September 26, 2019
By Edan Stanley
Gary Owens, MD, president of Gary Owens Associates, shares a payer perspective on treatment options for chronic lymphocytic leukemia, and weighs the benefits and challenges of using targeted therapy with ibrutinib compared with traditional chemoimmunotherapy.
Please introduce yourself and briefly explain your background.
My name is Gary Owens. I have more than 25 years of experience in the payer world managing both pharmacy and medical benefits. For the last 12 years, I have headed my own consulting organization providing strategic and tactical advice to developers of new medical technology, including drugs, devices, and diagnostics.
What are the most significant challenges in treating chronic lymphocytic leukemia (CLL)?
Many people live a long time with CLL, but in general, it is very hard to cure and early treatment hasn't been shown to help people live longer. Because of this and because treatment can cause side effects, clinicians often advise waiting until the disease is progressing or bothersome symptoms appear, before starting treatment.
CLL prognosis also varies considerably by mutational status, with some mutations conferring a better prognosis and others a much worse prognosis. Age and overall functional status also must come into play when considering treatment for CLL. Many patients with early stage disease simply required close monitoring. In fact, there are some sub-populations of CLL patients who have a survival rate similar to unaffected individuals of the same age.
From a payer’s standpoint, the treatments for CLL were not highly managed until the last few years. This change occurred because of the introduction of several newer treatment options that included targeted therapy, incorporating the Bruton's tyrosine kinase inhibitor (ibrutinib) or the BCL2 inhibitor (venetoclax) sometimes with an anti-CD20 monoclonal antibody (rituximab, obinutuzumab). These agents are now often used in place of more traditional chemoimmunotherapy using chemotherapy (eg, fludarabine, bendamustine, chlorambucil) plus an anti-CD20 monoclonal antibody. While the targeted therapies brought advances to the treatment of CLL, they introduced higher cost to payers and ultimately to patients who need them.
Can you explain some of the benefits of using ibrutinib compared to traditional chemoimmunotherapy?
Ibrutinib is FDA approved for both previously treated as well as untreated patients. It is an oral agent and appears to be well tolerated without some of the adverse effects of cytotoxic agents. We don’t know the optimal length of therapy yet, so most clinicians treat until the disease progresses. There does appear to be an increased risk of bleeding in patients treated with this agent.
Ibrutinib compared to ofatumumab showed superior response rates, improved PFS and improved OS. It also appears to be effective in patients who have poorer prognosis due to mutational status. Finally, there are relatively few non-responders.
In terms of the Oncology Care Model, what course of treatment is more cost-effective for payers? For patients?
While a recent study presented at AMCP shows that ibrutinib may be more cost-effective than chemoimmunotherapy, I am not sure we can say yet which treatment course may be the more cost-effective. The study found that cost offsets from factors like fewer hospitalizations and emergency room services offset the relatively higher cost of the agent. However, this was just a single study and subject to the limitations of retrospective claims database studies.
I think we have to wait until there is more clinical experience and more data to determine the most cost-effective regimen. For patients, the cost of this agent may be high as it is a specialty oral chemotherapy and likely to have substantial coinsurance burdens for Medicare beneficiaries. These patients comprise the majority of patients being actively treated for CLL.
What potential changes do you anticipate in treatment for Front-line CLL?
Many clinicians have already begun to use ibrutinib first line for reasons noted already. As data evolves about using this agent in combination with anti CD-20 agents and even with chemotherapy, newer patterns of treatment will continue to evolve. CLL continues to be an area of study including CAR-T therapies targeting CD-19, combinations of newer agents and investigational BTK inhibitors. I believe the treatment of CLL will continue to evolve as new data and new technologies come to market.