Treatment Strategies Expanding for Elderly Patients With CLL

Jacqueline Claudia Barrientos, MD

Combinations with chemotherapy and immunotherapy have historically not been an attractive approach for elderly patients with chronic lymphocytic leukemia (CLL), due to the comorbidities these patients likely already have.

“Chemoimmunotherapy regimens, such as fludarabine, cyclophosphamide, and rituximab (Rituxan; FCR) and bendamustine and rituximab (BR) do not work well because patients get infections, myelosuppression, and require blood transfusions or hospitalizations,” Jacqueline Claudia Barrientos, MD.

Therefore, studies are investigating novel approaches hoped to be better tolerated for elderly patients with CLL. For example, venetoclax (Venclexta) is being explored in combination with rituximab versus BR for patients with relapsed/refractory disease (NCT02005471).

OncLive: Can you provide an overview of your presentation on the management of elderly patients with CLL?

In an interview with OncLive, Barrientos, an associate professor at The Feinstein Institute for Medical Research at Northwell Health, discussed the appropriate treatment strategies for elderly patients with CLL. She shared insight on the topic in a presentation during the 35th annual CFS^®.Barrientos: The most important thing to understand is that elderly patients have many comorbidities that may affect their ability to tolerate a particularly therapy in CLL. By the time that these patients require therapy, most of them have at least 4 comorbidities, such as high blood pressure, cardiac disease, or are at high risk for kidney or liver disease.

We have new data on drugs such as the BTK inhibitor ibrutinib (Imbruvica) that work well. We have long-term follow-up of 31 patients who were treatment-naïve, older than 65, and received therapy 5 years later. Only 2 patients have stopped responding, one of which had Richter’s transformation at 6 months, whereas the other had progression due to a mutated BTK around 15 months out. However, the rest are in remission 5 years later.

We discussed the updated 3-year follow-up for the registration trial where 136 patients received ibrutinib with excellent response rates. Only 3 patients stopped responding, so it is a beneficial drug that will be the go-to regimen for elderly patients, as long as they are committed to take a daily pill for a longer period of time.

We discussed some combination regimens that are in the pipeline combining ibrutinib with obinutuzumab (Gazyva), which is a new monoclonal antibody. The German CLL Study Group did a combination study with bendamustine as a debulking agent for 2 cycles followed by obinutuzumab with ibrutinib in combination. For both regimens that are in combination with ibrutinib, one-third of patients experienced 100% response rates and complete remissions. When you do combination studies, the responses have been better—which we never thought was possible, following a 90% response rate as a single agent.

I also discussed venetoclax, which is currently approved in the United States for patients with relapsed/refractory disease and 17p deletion. I showed data of the breakthrough designation that the FDA is currently evaluating for venetoclax in combination with rituximab in patients with relapsed/refractory disease. Some of these patients can stop therapy because they have achieved a deep response, complete remission, and minimal residual disease negativity. Patients will not have to take this drug forever. The majority of patients who participated in those trials were older than 65.

What are the more common comorbidities that elderly patients with CLL may have?

The new era of drugs target the signaling pathway that is overexpressed and causes cell proliferation and survival of the malignant clone. This approach is better than chemotherapy, which is tough for many patients—particularly the elderly—to tolerate.The most common comorbidity is hypertension, which should be monitored. We are seeing over time that patients treated with ibrutinib can experience hypertension. Due to that, if the blood pressure is not controlled, the patient could be at risk for other side effects.

Additionally, many patients have cardiac risk factors that require them to be on antithrombotic agents or anticoagulants. Single-agent ibrutinib can cause higher prevalence and propensity to bleed. It is important to recognize this and tell patients to stop ibrutinib before they need surgical intervention to minimize the risk for bleeding. We do not know which patients will bleed, so we have a blanket statement for everyone. If they have surgery, they should stop the drug 3 to 7 days before and after and should not initiate any new treatment without discussing it with the physician.

If a patient is on an antifungal agent, it may affect the ability to metabolize an oral agent because the dose has been metabolized by the liver.