Four studies being presented today at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta highlight the multiple ways in which novel targeted cancer therapies are now being deployed to improve outcomes and quality of life for patients with rare, advanced, or difficult-to-treat blood malignancies.

Most standard chemotherapy drugs work by killing cells in the body that are growing and dividing rapidly; this includes cancer cells, but the drugs don’t distinguish between cancer cells and normal cells. Targeted drugs, by contrast, are designed to zero in on and neutralize genetic features of cancer cells that make them different from normal cells and allow the cancer cells to grow and spread. Because they are designed to specifically target cancer cells while leaving normal cells alone, targeted therapies usually have different, and sometimes milder, adverse side effects than standard chemotherapy drugs.

“These studies illustrate how better scientific understanding of what drives cancer at the molecular level is leading to novel therapies capable of keeping patients’ cancers in check for extended periods of time, while also helping them achieve better quality of life,” said press briefing moderator Laurie Sehn, MD, medical oncologist at the British Columbia Cancer Agency and clinical professor at the University of British Columbia in Vancouver, Canada.

In a large, international, randomized Phase III trial, patients with previously treated cutaneous T-cell lymphoma (CTCL) who received the investigational targeted drug mogamulizumab had significantly better progression-free survival, response rate, and quality of life than patients who received vorinostat, a US Food and Drug Administration (FDA)-approved standard-of-care treatment for patients with CTCL. The adverse events observed with mogamulizumab treatment were generally mild to moderate in severity.

The primary endpoint was progression-free survival—the time elapsed until the cancer began to show signs of getting worse—or death for any reason. Among 372 patients included in the trial, the median progression-free survival was 7.7 months for patients treated with mogamulizumab, compared with 3.1 months for those treated with vorinostat, reported lead study author Youn H. Kim, MD, professor of dermatology and director of the Multidisciplinary Cutaneous Lymphoma Program at the Stanford University School of Medicine.

“We found that mogamulizumab has convincing clinical activity, not just in skin, but also in clearing malignant T cells in the blood and lymph nodes,” said Dr. Kim. “Progression-free survival and overall global response outcomes are clearly superior, the side effects are tolerable, and we see measurable improvements in quality of life with mogamulizumab compared with vorinostat. Taken together, these findings represent a durable and clinically meaningful benefit for patients with CTCL.”

CTCL is a rare cancer of the white blood cells, specifically T lymphocytes, that primarily occurs in the skin. It is caused when T cells (cells in the immune system that help the body fight infection) begin to grow uncontrollably and build up in the skin. CTCL can also involve the blood, lymph nodes, and internal organs.

Mogamulizumab targets a protein (CCR4) that is frequently found on the surface of cancer cells in patients with CTCL. As a CCR4 antibody, the drug exploits the patient’s immune cells to attack the cancer, Dr. Kim explained. Vorinostat, one of several drugs approved by the FDA to treat CTCL, works by blocking the action of an enzyme that helps cancerous T cells survive and multiply.

Adverse effects, such as diarrhea, nausea, altered taste, decreased appetite, increased blood creatinine levels, and decreased platelet counts, occurred more than twice as frequently in patients treated with vorinostat than in those treated with mogamulizumab, said Kim. By contrast, the adverse effects seen most frequently in patients treated with mogamulizumab were drug rash and infusion-related reactions, such as chills and flushing. Mogamulizumab was administered as a once-weekly intravenous infusion for the first 28-day cycle and every 2 weeks during subsequent cycles. Vorinostat was taken as a once-daily pill.

Dr. Kim says the next step will be to learn more about biomarkers that can predict treatment outcome, and to test whether clinical benefit can be further improved by combining mogamulizumab with skin-directed or other systemic therapies that have different mechanisms of action.