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Health & Medicine for Senior Citizens

Seniors with Chronic Lymphocytic Leukemia Do Poorly on Therapy Designed for Younger Patients

People who develop chronic lymphocytic leukemia (CLL) are typically age 65 and older, but participants in CLL clinical trials are usually several years younger

Dec. 12, 2012 – Although most people are age 65 or older – senior citizens – when they develop chronic lymphocytic leukemia (CLL), most of the clinical trials use younger participants. And, age is not usually considered when treatment is determined. A new study says this is a mistake – the therapies should be different for older CLL patients and younger ones, although the disease is incurable.

 

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This study, led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), indicates that older people with CLL may not respond as well to the therapy used for most patients.  It was published Dec. 10 in the Journal of Clinical Oncology.

 “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 – James.

“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.

About Chronic Lymphocytic Leukemia

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood cells.

These cells crowd out the healthy blood cells, making it hard for blood to do its work. In chronic lymphocytic leukemia (CLL), there are too many of a specific type of white blood cell called a lymphocyte.

CLL is the second most common form of leukemia in adults. It often occurs during or after middle age and rarely occurs in children.

From 2005-2009, the median age at diagnosis for chronic lymphocytic leukemia was 72 years of age. Approximately 0.0% were diagnosed under age 20; 0.2% between 20 and 34; 1.6% between 35 and 44; 9.0% between 45 and 54; 20.9% between 55 and 64; 26.5% between 65 and 74; 27.8% between 75 and 84; and 14.0% 85+ years of age.

The age-adjusted incidence rate was 4.2 per 100,000 men and women per year.

From 2005-2009, the median age at death for chronic lymphocytic leukemia was 79 years of age. Approximately 0.0% died under age 20; 0.1% between 20 and 34; 0.4% between 35 and 44; 2.9% between 45 and 54; 10.7% between 55 and 64; 20.8% between 65 and 74; 35.1% between 75 and 84; and 29.9% 85+ years of age.

The 4 Common Types of Leukemia

Chronic lymphocytic leukemia (or chronic lymphoblastic leukemia, CLL) accounts for about 7,000 new cases of leukemia each year. Most often, people diagnosed with the disease are over age 55. It almost never affects children.

Acute lymphocytic leukemia (or acute lymphoblastic leukemia, ALL) accounts for about 3,800 new cases of leukemia each year. It is the most common type of leukemia in young children. It also affects adults.

Chronic myeloid leukemia (or chronic myelogenous leukemia, CML) accounts for about 4,400 new cases of leukemia each year. It affects mainly adults.

Acute myeloid leukemia (or acute myelogenous leukemia, AML) accounts for about 10,600 new cases of leukemia each year. It occurs in both adults and children.

>> More on Chronic Lymphocytic Leukemia (National Library of Medicine)

“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.

Other researchers involved in this study were Amy S. Ruppert and Susan Geyer of Ohio State; Kanti Rai and Jonathan Kolitz of North Shore-Long Island Jewish Medical System; Martin S. Tallman, Memorial Sloan-Kettering Cancer Center; Thomas S. Lin, GlaxoSmithKline; Frederick R. Appelbaum, Fred Hutchinson Cancer Research Center; Andrew R. Belch, Cross Cancer Institute, Edmonton, Alberta, Canada; Vicki A. Morrison, University of Minnesota and Veterans Affairs Medical Center; and Richard A. Larson, University of Chicago.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S. News & World Report.

 

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