Zosia Chustecka

December 01, 2010

December 1, 2010 — Novel drugs for hematologic malignancies will be headlining the news coming out of the American Society of Hematology (ASH) 52nd Annual Meeting, which starts this weekend in Orlando, Florida.

A glimpse at some of the research that will be presented comes from an interview with ASH secretary Charles Abrams, MD, associate chief of the Division of Hematology/Oncology at the University of Pennsylvania in Philadelphia.

Major Step Forward in Lymphoma

A new drug that has already generated some excitement is brentuximab, which is approaching the market for use in relapsed and refractory Hodgkin's lymphoma. This indication is considered an unmet medical need, so it has been granted both orphan-drug and fast-track status by the US Food and Drug Administration.

Brentuximab is also being considered for relapsed and refractory anaplastic large cell lymphoma, which can be a very difficult disease to treat, said Dr. Abrams. "This is what killed Jackie O," he added.

Results from 2 pivotal phase 2 trials that looked at these 2 indications will be presented in full at the meeting (abstracts 283 and 961).

Some details of the results were released and reported after they were presented at the International Symposium on Hodgkin Lymphoma in Cologne, Germany. In addition, earlier data from a phase 1 study were published recently in the New England Journal of Medicine (2010;363:1812-1821).

The data already released show that brentuximab produces very high response rates in both types of lymphoma in patients who have failed other treatments and who have no other therapeutic options.

Dr. Abrams said that the data on brentuximab so far are "very encouraging." They offer the hope that, if the drug is used in combination with chemotherapy, it will show even better responses.

Progress in CML

Another new drug highlighted by Dr. Abrams was ponatinib, which is directed at chronic myeloid leukemia (CML). Although this drug is a tyrosine kinase inhibitor and is a follow-on to imatinib (Gleevec) and its successors, ponatinib is novel in that it is active against the T315I mutation, for which there are currently few treatment options.

The ponatinib data (abstract 210) come from a phase 1 trial of patients with refractory CML who had failed 2 or more tyrosine kinase inhibitors; the response rate was very high. Although these data are early, they offer hope for CML patients who are refractory to the drugs that are already available, Dr. Abrams said.

Another presentation with good news for the CML field reports data from a 3-year follow-up of the Italian GIMEMA trial looking at nilotinib (abstract 359). These results are "outstanding," Dr. Abrams noted; the progression-free survival rate in this trial was 99%.

"It's very reassuring to have long-term data on these drugs," he added, and it shows that a majority of patients respond and continue to respond.

Highlights From the Plenary Session

One of the highlights of the plenary session is the very first presentation (abstract 1), which offers new details about TET2 mutations in myeloid leukemias. "This is a common mutation in leukemia, but how it works has not been previously known," Dr. Abrams explained.

These researchers determined that TET2 plays a role in the hydroxylation of a component of DNA. "Mutations within TET2 impair this process." Dr. Abrams explained. "It is certainly possible that the TET2 mutations are inducing leukemia. If this is true, one could theoretically develop a drug that would compensate for a TET2 mutation," he said.

Another highlight from the plenary session is a presentation (abstract 6) that offers new data on the controversy over when to start rituximab in the treatment of follicular lymphoma.

"In the United States, it has been common practice to start rituximab early on, even in patients who are asymptomatic, whereas in Canada and Europe and the rest of the world, the approach has been more conservative. Early use of rituximab is not standard of care worldwide," Dr. Abrams explained.

These new data come from a "very high-quality study" and show that there is a clear advantage to starting rituximab therapy early on, not waiting until symptoms develop, Dr. Abrams said. There was a clear improvement in progression-free survival, although not in overall survival, he added. He predicts that these new data will lead to practice changes, not so much in the United States, but elsewhere in the world.

Also in the plenary session is a presentation that offers a new approach to combating malaria (abstract 2). It focuses on a protein that is involved in the breakdown of heme, which is toxic to the malaria parasite and the mosquito. The hope is that targeting this protein and inhibiting its breakdown of heme will result in a build up of heme concentrations that will kill the malaria parasite. "This a great piece of science. It is certainly promising, but the story is not complete yet," Dr. Abrams noted.

Follow-Up of Transplant Donors

"There's a very nice study" among the transplantation abstracts, reported Dr. Abrams, which looked at the general health of allogeneic stem-cell donors for years after they donated (abstract 365).

"There's always been a hesitation over this, particularly among individuals who are donating to strangers, with some concern about 'What's going to happen to me?' " he explained. The informed consent forms that these individuals sign list a great many potential risks and possibilities of what might happen, but this follow-up of more than 15,000 donors shows that "they really do great, and there is not much to fear from being a donor," he said. "I do think this is material that is worth disseminating," Dr. Abrams said.

Noncancer Hematology Research

There are also several notable abstracts in the noncancer areas of hematology, Dr. Abrams said.

One presentation (abstract 843) features hydroxyurea in the treatment of sickle cell disease. This drug has been used in adults, but not much in children," Dr. Abrams explained. "Maybe we should be using it more," he noted, because these new data, from Brazil, show that hydroxyurea reduces mortality when used in children. However, the study was retrospective, so the conclusions are limited, he added.

A late-breaking abstract (abstract LBA-1) focuses on acute pulmonary embolism, which is a considerable cause of mortality.

"In the United States, patients with pulmonary embolism are treated in hospital as inpatients," Dr. Abrams explained, but this HESTIA study out of Europe showed that certain patients with pulmonary embolism — patients who met a very rigidly described selection criteria — could be treated safely with low-molecular-weight heparin as outpatients.

"This is the best evidence yet that some patients with pulmonary embolism can be treated as outpatients," Dr. Abrams said. This is more convenient for the patient, and potentially safer, because being admitted to a hospital always exposes patients to potential infections and complications.

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