Newer Therapies Make Inroads Against Adult Leukemias

Christopher N. Bredeson, MD, MSc, FRCPC, is a Medical College of Wisconsin Associate Professor of Medicine with tenure (Neoplastic Diseases, Bone Marrow Transplant), and Director of Hematological Malignancies. He practices at the Froedtert & Medical College Neoplastic Diseases and Related Disorders clinic.

In Researchers Are Changing Leukemia Treatments and Outcomes, Dr. Bredeson discussed types of leukemia and the remarkable progress of leukemia research, particularly in finding new treatments for children. Here, Dr. Bredeson describes recent advances in the treatment of three types of leukemia that affect adults.

Acute Myeloid Leukemia
Although acute myeloid leukemia (AML) occurs in people of all ages, "the majority of patients are in their 60s or older," notes Dr. Bredeson. "There are some new medications being studied that I believe hold promise to improve the management of elderly patients with AML."

Older adults have a harder time tolerating traditional chemotherapy, and Dr. Bredeson says their rate of response to traditional chemo isn't satisfactory. "With chemotherapy, less than half of people in their 60s will go into remission with their disease coming under control," he notes.

The problem is that chemotherapy kills every dividing cell, both good and bad, resulting in side effects - such as nausea, fatigue, and increased risk of infection - that can create additional problems for people who are already ill.

Newer therapies work in a different way and typically have fewer debilitating side effects, Dr. Bredeson explains. "They address some of the abnormalities in the chromosomes. By somewhat sophisticated methods, laboratory researchers have figured out some of what is wrong in the bone marrow and how to attempt to reverse those processes. The therapies basically try to turn on genes that have been turned off.

"The theory is that if you can turn on genes that tell the cell what to do properly, you can make cells that have gone bad become more normal. Or, you can turn on signals that tell the cells to kill themselves, which is what bad cells are supposed to do. These therapies were developed initially for what we used to call pre-leukemia, or MDS (Myelodysplastic Syndrome). "One is called Dacogen (decitabine) and the other is called Vidaza (azacitidine). They have been used in studies of certain older patients with AML with promising results.

"Another type of new agent for leukemia called vorinostat (brand name Zolinza) is being developed to turn on good genes that have been turned off in leukemia cells by a different mechanism. We recently opened a trial combining vorinostat with decitabine to treat older patients with MDS and AML."

Chronic Myeloid Leukemia
"Chronic Myeloid Leukemia (CML) is a very interesting illness," says Dr. Bredeson. "It is a stem cell disorder, meaning that one of the very early cells in the bone marrow has gone wrong, but it has gone wrong in a very specific way related to a very specific rearrangement of chromosomes. It turns on a signal in the cell; we don't understand exactly why it makes the cells behave abnormally, but we know that if we block that signal the disease comes under control.

"There have been great advances in treatment for CML. Gleevec (imatinib) - a drug that is now very well known after coming on the market within the last five years - is a small molecule that blocks the signal that is produced by malignant cells. This drug has changed CML from an acute illness for which the only good therapy was to have a bone marrow transplant, to an illness that in the vast majority of patients is now well managed by taking a pill. In addition to imatinib, there are 2 other targeted therapies for CML that have been more recently approved, dasatinib (Sprycel) and nilotinib (Tasigna).

"This has revolutionized the management of a particular leukemia and brought a lot of focus and interest to what we call 'targeted therapy'. Drugs in targeted therapy are really great for older patients who wouldn't be candidates for transplant because of illness, physical conditions or just age. The majority of people who get CML are over the age of 60, and we didn't really have a specific therapy for them.

"Now we have this great therapy that so far has kept people's disease under control for quite a long period of time. I don't know that anybody uses the word 'cure', but if you're in your 70s and you can control something for five or ten years that's a reasonable start."

Dr. Bredeson notes that bone marrow transplantation still has a role for younger patients, patients who have more aggressive forms of the disease, or those who don't respond to the newer medications.

Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia (CLL) is also a disease of the older population; the median age of onset is in the 60s so the vast majority of patients are seniors. Symptoms of the disease can vary significantly between individuals, Dr. Bredeson says.

"Not everyone with CLL is the same. Some have a very indolent, slowly progressing disease that is found most often by chance through an unrelated blood test. These patients may not need treatment for three or five or ten years. Other patients have a very aggressive form of CLL where the cells are turning over much more quickly; these patients need to be treated."

As with AML and CML, "There have been significant developments in CLL treatment," Dr. Bredeson notes. "There has been progress in identifying markers that help the clinician decide whether the CLL is going to be indolent or more aggressive. And there has been some development of new therapies that have probably changed the natural history of the disease. Although the disease is still thought to be incurable, there are more options to manage it so that overall people with CLL will live longer with a good quality of life.

"That's been accomplished in part through newer types of targeted therapy - antibody therapies - that have been developed, such as Rituxan (rituximab) and Campath (alemtuzumab)."

The Goal of Cure
Although these are less intensive therapies may be more broadly applicable, Dr. Bredeson says it is important to remember that for many patients the potential for cure of their disease remains an attainable goal. As the "baby boom" generation enters their 60s, many of them remain in good general health, allowing for the possibility of curative therapy with "reduced intensity" stem cell transplants for some older leukemia patients.

Medical College Disease Specialists
Dr. Bredeson notes that the Medical College is fortunate to have specialist on hand to deal with theses diseases. "The care of patients with leukemia is changing rapidly with the introduction of new therapies. In order to best manage these illnesses it is important for the physician to focus on that patient population.

"At Froedtert & Medical College of Wisconsin, we have physicians who lead care teams focused on the treatment of patients with leukemia. Along with Timothy Fenske, MD, MS, Assistant Professor of Medicine (Neoplastic Diseases and Related Disorders) who has focused expertise and interest in CLL and ALL, Ehab Atallah, MD, Assistant Professor of Medicine (Neoplastic Diseases and Related Disorders) recently joined our faculty after completing a clinical leukemia fellowship at MD Anderson Cancer Center. Dr Atallah brings significant new clinical expertise in the care of patients with all types of leukemia to Froedtert & Medical College of Wisconsin.

"In addition to state-of-the-art clinical care, at Froedtert & Medical College, these physicians lead a wide variety of clinical trials for patients with leukemia to consider along with standard therapies," Dr. Bredeson notes.

Research Continues
Dr. Bredeson has been encouraged that new therapies - some in use and some in development - have already begun to provide better outcomes for older leukemia patients. Recent developments in the fields of genetics, genomics, and information technology have led to dramatic advances in cancer research, diagnosis, and treatment. As progress in these areas continues to intensify, more discoveries are bound to be made, leading to better outcomes for adults with leukemia.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.