Older and younger chronic leukemia patients may need different therapy

Doctors should use different therapies when treating older and younger patients with chronic lymphocytic leukemia, according to a new study.

• People who develop chronic lymphocytic leukemia (CLL) are typically age 65 and older, but participants in CLL clinical trials are usually several years younger;
• The age of CLL patients is not usually considered when determining treatment;
• This study suggests that older and younger CLL patients require different therapy.

Age is usually not considered when determining treatment for people with CLL, but this study indicates that older people with CLL may not respond as well to the therapy used for most patients.

“Our analysis shows that optimal therapy for younger and older patients with chronic lymphocytic leukemia is likely to be different, at least when using current treatments,” says first author Dr. Jennifer Woyach, assistant professor of hematology at the OSUCCC.

“We hope this study will shape future research by highlighting the importance of enrolling older patients on clinical trials and of developing trials that specifically target older patients.”

Doctors diagnose about 15,000 new cases of chronic lymphocytic leukemia (CLL) annually in the United States, making it the most common form of leukemia. It remains incurable, and about 4,400 Americans die of the malignancy each year. CLL most often occurs in people older than age 65; the average age at diagnosis is 72. Yet, most

CLL clinical-trial participants are in their early 60s.

“Our findings apply to both routine care of CLL patients 70 years and older and to future CLL trials,” says principal investigator Dr. John Byrd, a CLL specialist and professor of medicine, of medicinal chemistry and of veterinary biosciences at the OSUCCC – James.

“The study suggests that chlorambucil is superior to fludarabine in older patients, and that CD20 antibody therapies such as rituximab are beneficial as front-line therapy for all CLL patients, regardless of age,” says Byrd, who is the D. Warren Brown Designated Chair in Leukemia Research.

“These data also show that future treatment trials for older adults with CLL should build on CD20 antibody therapies such as rituximab and ofatumumab, but not on fludarabine or alemtuzumab.”

Byrd, Woyach and their colleagues reviewed 663 CLL patients who were enrolled in four sequential CLL clinical trials evaluating front-line therapies. The researchers looked for differences in treatment outcomes between older and younger patients to identify the most effective therapy for older adults.

The four trials, all sponsored by the Cancer and Leukemia Group B (CALGB) clinical cooperative group, compared these treatments: chlorambucil versus fludarabine, fludarabine plus rituximab versus fludarabine, fludarabine with consolidation alemtuzumab, and fludarabine plus rituximab with consolidation alemtuzumab.

Key conclusions include:

• Fludarabine versus chlorambucil: Fludarabine improved progression-free survival and overall survival among patients younger than age 70 but chlorambucil tended to produce higher overall survival in patients older than 70.
• Rituximab combined with fludarabine, versus fludarabine alone, improves progression-free and overall survival in both younger and older patients.
• Alemtuzumab consolidation therapy after chemotherapy or chemoimmunotherapy does not improve progression-free or overall survival in either younger or older patients

Funding from the NIH/National Cancer Institute (grants CA31946, CA33601 and CA140158), the Leukemia and Lymphoma Society, the Harry Mangurian Foundation and the D. Warren Brown Family Foundation supported this research.

The study was published in the Journal of Clinical Oncology.