Clinicians Should Consider Specific Factors When Determining Optimal Therapy Sequencing for CLL
In order to optimize therapeutic sequencing among patients with chronic lymphocytic leukemia (CLL), clinicians should consider five patient characteristics, according to a presentation at the 35th Annual Chemotherapy Foundation Symposium (November 9-11, 2017; New York, NY).
According to Kanti R Rai, MD, The Feinstein Institute for Medical Research (North New Hyde Park, NY), optimizing treatment for patients with CLL requires sequencing based consideration of a regimented order of patient characteristics. Among the five patient aspects that must be taken into consideration include 17 p deletion or TP53 abnormalities, IgVH mutation status, age, previous treatment status, and performance status.
Dr Rai explained that 17p mutation status must first be identified for treatment-naïve patients. Prior research has shown that patients with the 17p deletion or TP53 mutation often do not respond to chemoimmunotherapy. For patients with the 17p deletion or TP53 mutation who achieve a response, the duration of response tends to be brief. Additionally, patients with the IgVH mutation have a significantly worse prognosis.
For patients who do not have the 17p deletion, Dr Rai explained that clinicians should then consider patient age (relative to 65 years) and performance status (whether the patient is fit, less fit, or unfit based on scores from ECOG or Karnofsky measurements). CLL occurs at a higher rate in older patients who have a greater number of comorbidities. Older patients’ ability to withstand the toxicities of treatment must also be taken into consideration.
Dr Rai further explained that younger patients who are deemed fit and without the 17p deletion and with mutated IgVH should be given chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab as an initial therapy. On the contrary, older patients with similar characteristics should be given bendamustine plus rituximab, or obinutuzumab plus chlorambucil.
Those who are less fit and without the 17p deletion should initiate bendamustine plus rituximab, or ibrutinib as a frontline therapy, followed by obinutuzumab plus chlorambucil as a second-line therapy. Unfit patients with comorbidities with or without the 17p deletion should be given ibrutinib or obinutuzumab plus chlorambucil, while unfit patients with the 17p deletion or with TP53 abnormalities should begin treatment with ibrutinib, Dr Rai concluded.—Zachary Bessette