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Drug test results signal hope in leukemia fight

By DR. V. UPENDER RAO
Published February 12, 2007

At the 48th annual meeting of the American Society of Hematology, researchers from the Roswell Park Cancer Institute in Buffalo, N.Y., presented impressive results of a clinical trial for patients with chronic lymphocytic leukemia, treated with lenalidomide (Revlimid). They reported results of a phase II study of 45 patients with CLL who had either relapsed or become refractory to standard treatments.

They were treated with 25 mg tablets of Revlimid daily for 25 days each month. Twenty-six of the 45 patients responded to the treatment favorably. Six patients achieved a complete remission and 20 registered a partial response, for an overall response rate of 57.7 percent.

The side effects were predictable and manageable. The elevated white blood cell counts started to decrease within days from the beginning of the treatment with Revlimid. Dr. Asher A. Channan-Khan, assistant professor of medicine and one of the researchers involved in this study, said, "These are groundbreaking and amazing results."

He said that the traditional treatments focused on killing the tumor cell but did not address the microenvironment.

Revlimid is a significantly more potent analog of the older drug Thalidomide. It has anti-angeogenic properties and works on the microenvironment of the leukemic cell rather than on the cell itself. It causes the neighborhood in which the leukemic cell resides to become hostile and unfavorable to its survival. It also stimulates the body's immune system against the leukemia.

Side effects consisted of fatigue and low blood counts. Eighty percent of the patients experienced a "flare" reaction, consisting of tender enlargement of lymph nodes, liver and spleen along with rash, fever and increasing white blood cell count.

Although it could be interpreted as progression of leukemia, it was typically transient and did not require treatment interruption. In fact, patients experiencing the more intense reaction achieved greater clinical responses.

The "flare" reaction was thought to represent the initial phase of the body's immune response against leukemia.

Eliciting a response rate of greater than 50 percent, together with some complete remissions in patients who had failed standard treatments and had become refractory, is impressive. These results deserve to be validated in larger trials.

One such trial is accruing patients with refractory CLL here at the Cancer and Blood Disease Center.

The battle against CLL and other malignancies should perhaps be fought on two fronts: against the microenvironment with Revlimid and related drugs, and against the malignant cell itself with proven chemotherapy and or biological treatments.

In the past, there had been a more laid-back attitude in the management of CLL because some patients do live for many years without requiring any treatment and eventually succumb to unrelated causes. However, the majority of patients will die of the disease, some within three years of diagnosis.

Some develop a more intense form of the disease known as prolymphocytic leukemia and others transform into aggressive forms of non-Hodgkin's lymphoma.

CLL patients and their families are also at higher-than-normal risk for other solid tumors. Tests to identify the varying prognosis of CLL patients are now available, with more in the pipeline.

The traditional treatments, which focused only on bringing down the elevated lymphocyte count, are now largely archaic. Modern management aims at not just normalizing the blood and achieving a normal-looking bone marrow, but also at eradicating the CLL clone altogether.

When this can be achieved, CLL can change from a manageable disease to a curable disease. Revlimid may be one important step in that direction.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified February 11, 2007, 19:47:21]