Molecular Therapies Tackle Blood Cancers

SUNDAY, June 4, 2006 (HealthDay News) -- Breakthrough molecular therapies like Gleevec are dramatically increasing survival rates for patients with certain blood cancers.

That good news, delivered Sunday at the American Society of Clinical Oncology annual meeting in Atlanta, raises the possibility that bone marrow transplants, once the last hope for these patients, will become a thing of the past.

"These therapies will force transplants to adapt to changing paradigms," said Dr. Mark H. Kirschbaum, director of new drug development for hematology malignancies at City of Hope, in Duarte, Calif. "This is the big revolution. Now you can treat with a pill, and it holds up."

These agents, which include Gleevec (imatinib) and Thalomid (thalidomide), offer the promise of starkly more effective therapies for other cancers in the future as well, according to the new research.

In the largest follow-up study on Gleevec, which has been called a wonder drug, five-year data showed that overall survival for people with chronic myeloid leukemia (CML) was 89 percent (95 percent if only deaths related to CML were considered). At the same time, 93 percent still had not progressed from the chronic to the acute phase of the illness.

"This study confirms Gleevec as the standard first-line therapy for patients with CML," said study author Dr. Brian J. Druker, a professor of medicine at Oregon Health and Science University in Portland.

Gleevec blocks the activity of a gene that plays a significant role in the disease, thereby reversing the malignancy process.

The 1,106 participants in this trial, which was funded by the drug's maker Novartis, were randomized to receive either Gleevec or the standard treatment, interferon plus cytarabine arabinoside. Patients in the interferon arm were allowed to cross over to the Gleevec arm at any time during the trial. So many switched that by the end of the study, only 3 percent remained in the standard treatment arm. Only 5 percent of participants had to discontinue Gleevec because of side effects.

Rate of side effects and of progression to the acute phase of the disease continued to decline the longer the person was on the drug.

Of the 553 patients originally assigned to Gleevec, 96 percent to 98 percent saw their blood counts return to normal. At one year, 69 percent saw a correction of the genetic mutation. By the end of five years, that number had risen to 87 percent.

The best five-year survival previously reported was 65 percent, Druker said, although overall survival generally was in the 45 percent to 65 percent range.

Druker and his research team are in the final stages of comparing Gleevec with another targeted agent, dasatinib. He is currently using Gleevec for some of his patients.

"Given the high response rate and good tolerability and long-term data, I'm starting with imatinib for now," he said. "We have not yet cured CML. Our patients remain on therapy and remain on therapy long-term."

Two other studies looked at the role of thalidomide in the treatment of multiple myeloma, a cancer of the bone marrow which is considered incurable.

Thalidomide has a checkered history, having caused birth defects in the babies of women who were taking it as a sleep aid in the 1960s. It has been used experimentally to treat multiple myeloma since the late 1990s.

In one of the new studies, elderly patients (aged 65 to 75) who took 400 milligrams of Thalomid daily had longer overall survival (53.6 months) than those taking the standard treatment (32.2 months) or the standard treatment plus stem cell transplantation (38.6 months). The results were encouraging enough that the study was halted so all patients could benefit from Thalomid.

"This study was the first and only study to evaluate thalidomide in combination with standard therapy vs. both standard therapy and stem cell transplantation," said study author Dr. Thierry Facon, a professor of hematology at the University of Lille in France. "The thalidomide arm had a significant survival advantage."

Side effects were considerably higher in the thalidomide group, however, and included blood clots and neuropathy.

The second study, from the same university, looked at a lower dose of thalidomide. This 100-milligram dose appeared to be just as effective with fewer side effects, said study author Dr. Ibrahim Yakoub-Agha, a hematologist at the university.

"In the old chemotherapy-based model, more was better and, increasingly, we are learning with molecular agents that less is more," Kirschbaum said.

Finally, a study showed that a specific molecular marker may help predict whether patients with acute myeloid leukemia (AML) will experience a relapse after treatment.

But thanks to the onward roll of new treatments, the patients who do not respond to conventional chemotherapy may well benefit from new molecular treatments, Kirschbaum noted.

"This is how the world is going to look," he said.

More information

The Leukemia and Lymphoma Society has more on blood cancers.