Jacqueline Claudia Barrientos, MD
Physician, CLL Research and Treatment Program
North Shore-LIJ Cancer Institute
New Hyde Park, NY
The treatment landscape for patients with chronic lymphocytic leukemia (CLL) is rapidly changing, with the emergence of four new therapeutic options for this malignancy in recent months.
In November 2013, the FDA approved obinutuzumab (Gazyva) in combination with chlorambucil for patients with previously untreated CLL. Earlier this year, ibrutinib (Imbruvica) was approved for patients who have had at least one prior therapy, and more recently gained an indication for therapy in patients with 17p deletion (including treatment-naïve patients).
In addition, ofatumumab (Arzerra) in combination with chlorambucil gained an indication for patients with previously untreated CLL who are not candidates for fludarabine-based therapy. And most recently, idelalisib (Zydelig) in combination with rituximab was approved for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to other existing medical conditions.
Jacqueline Claudia Barrientos, MD, has conducted research into emerging CLL compounds and is a practicing physician at North Shore–LIJ Cancer Institute in New Hyde Park, New York, a component of the North Shore–LIJ Health System. She discussed some of the considerations confronting oncology specialists treating patients with CLL in light of the new options available.OncologyLive: What are the standard treatments for patients with relapsed or refractory CLL, and on what basis do you choose between them?Barrientos
: Today, the standard of care for initial therapy in young and fit CLL patients is a combination with a purine analog and a monoclonal antibody, such as fludarabine + cyclophosphamide + rituximab (also known as FCR). Unfortunately, most patients with CLL are elderly with multiple comorbidities and are not able to tolerate such intensive regimens.
If a patient achieves a long period of remission after the initial treatment (eg, 4 years or more), it would be reasonable to consider using the same chemoimmunotherapy used previously. However, most physicians often choose a different regimen, such as bendamustine + rituximab (BR), which has been shown to have good activity in relapsed disease with a good safety profile, because it is a “gentler combination” that is easier to tolerate. The monoclonal antibody ofatumumab is also used as a single-agent therapy in relapsed disease, since the drug has been shown to have activity in fludarabine-refractory and alemtuzumab-refractory patients. The choice of therapy depends on the patient’s comorbidities and preference. Alemtuzumab used to be an option for relapsed CLL, but its use has fallen out of favor due to increased risk of infections (like cytomegalovirus reactivation).
The Bruton tyrosine kinase inhibitor ibrutinib was recently approved as monotherapy for the treatment of relapsed CLL and in patients with 17p deletion. Ibrutinib has excellent activity in relapsed or refractory disease, including among patients with high-risk disease, such as those with the dreaded 17p deletion. The drug is well tolerated even in patients with multiple comorbidities with minimal toxicities that include diarrhea, fatigue, and infection. Most importantly, ibrutinib has significant clinical activity in patients who have failed multiple prior regimens, and the drug is showing durable remissions never before seen in this cohort of patients with multiple prior lines of therapy.1What outcome measures are the most useful for assessing treatment response in patients with relapsed/refractory CLL?
Ideally, the best regimen to choose is the one where the patient will have the best response for the longest period of time with the lowest level of toxicities. Even though chemoimmunotherapeutic approaches have been the standard treatment options for patients with relapsed disease, the recent approval of new targeted agents (that are better tolerated with excellent responses and long remission durations) will likely lead to many patients living longer.How do patients’ status with regard to genetic risk factors, such as del(17p13.1), affect the choice of treatment?
The best single agent available for patients with 17p deletion is ibrutinib. Data presented at this year’s American Society of Clinical Oncology meeting showed that median progression-free survival for this particular patient population was 28 months,1
and this is the best remission duration that I have seen for any agent, approved or in clinical trials.