Clinical trials show benefit for lymphoma patients @ASH

A drug approved for treating resistant versions of two types of lymphoma knocked down the disease in all 26 patients evaluated in a phase I clinical trial of front line use combined with chemotherapy.

Michelle Fanale, M.D., assistant professor in MD Anderson's Department of Lymphoma and Myeloma presented results of the trial at the 54th American Society of Hematology Annual Meeting and Exposition in Atlanta.

The trial provides evidence that the drug brentuximab vedotin (ADCETRIS, developed by Seattle Genetics, Inc.) potentially could be brought forward to front line treatment and could be used to treat additional types of non-Hodgkin lymphoma.

A combination of brentuximab vedotin with a chemotherapy combination called CHP produced complete remissions in 23 of the 26 patients, who had either systemic anaplastic large cell lymphoma (19 patients) or a CD30-positive mature T cell or natural killer cell lymphoma (seven patients). The other three had partial remissions.

All seven of the mature T cell or natural killer cell lymphoma patients had a complete remission.

Brentuximab targets the CD30 surface protein, which is heavily expressed on Hodgkin lymphoma and in ALCL but rarely found on normal cells. The drug consists of an antibody that connects to CD30 and a potent chemotherapy drug that blocks cell division after it's taken into the lymphoma cell.

On this trial, the drug was combined with CHP, which includes cyclophosphamide, doxorubicin and prednisone.

A phase 3 trial is planned for next year that will compare the brentuximab vedotin/CHP combination to another chemo combination known as CHOP, which is CHP plus vincristine, for front line treatment of mature T cell lymphomas.

Fanale led the clinical trial of brentuximab vedotin that resulted in its approval by the U.S. Food and Drug Administration for resistant Hodgkin lymphoma or ALCL. It was the first new drug for Hodgkin lymphoma in 30 years.

Manageable side effects that occurred in greater than 30% of cases included nausea, peripheral neuropathy, diarrhea, fatigue, hair loss, constipation, shortness of breath, and fever with reduced levels of white blood cells.

Ibrutinib is safe and active against relapsed follicular lymphoma

A drug that attacks a protein involved in B cell malignancies gained a great deal of attention at ASH for its ability to attack chronic lymphocytic leukemia in phase 2 trials alone and in combination with rituximab (Rituxan) .

Tomorrow, Michael Wang, M.D., associate professor in MD Anderson's Department of Lymphoma and Myeloma, presents phase 2 results that show "unprecedented impact" by the drug in mantle cell lymphoma.

Sunday, Nathan Fowler, M.D., an assistant professor in lymphoma and myeloma, presented phase 1 results that showed the drug is tolerated and active against relapsed follicular lymphoma.

Eleven of 16 patients in the trial could be evaluated for the drug's efficacy. Of those, six had their disease respond to the drug -- three complete remissions and three partial remissions. Duration of response was 12.3 months and median progression-free survival was 13.4 months.

Two patients were still responding to ibrutinib at 25 and 29 months.

No dose-limiting side effects were observed in those in those receiving the highest dose, so a maximum tolerated dose was not reached.

Common side effects included diarrhea, fatigue, nausea, cough, muscle pain. Grade 3 adverse events included anemia, anxiety, hypersensitivity, reduced potassium levels, pneumonia and low white blood cell levels.

Bruton's tyrosine kinase is a mediator of B cell receptor signaling, which is essential for normal B cell development and overactive in cancerous B cells. Ibrutinib inhibits Bruton's , causing cell death and decreasing cellular migration and adhesion in malignant B-cells.

Ibrutinib was developed by Pharmacyclics, Inc.