Research Activities, March 2014
No therapy better than another for advanced-stage chronic lymphocytic leukemia
As the most commonly diagnosed lymphoid malignancy, chronic lymphocytic leukemia (CLL) develops in older patients. Since CLL is incurable, therapies are used to control disease progression and complications. Clinicians can select from a wide variety of treatment options, from single agents to combination-based chemotherapies. A recent meta-analysis compared studies of various first-line therapies to determine their efficacy and overall survival. No evidence was found that any treatment was better than another. In fact, newer therapies did not show a survival advantage over chlorambucil monotherapy introduced in the 1960s.
The study consisted of a 30-year overview of 25 randomized controlled trials evaluating 10 treatments for CLL in approximately 7,800 patients. In addition to single-agent chlorambucil, other therapies evaluated were single-agent fludarabine, cladribine, alemtuzumab, and bendamustine. Combination treatments were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or similar conventional combinations, and cyclophosphamide or similar conventional chemotherapies combined with fludarabine or cladribine. There were also two other triple-therapy combinations evaluated: fludarabine, cyclophosphamide, and rituximab and pentostatin, cyclophosphamide, and rituximab. Patients were relatively young, in their late 50s and 60s, and were considered uncomplicated cases of CLL.
After evaluating combined direct and indirect data, the researchers found that no one single treatment option was significantly better than others when it came to overall survival. Bendamustine and fludarabine-rituximab-based chemotherapy, two newer approaches, had longer progression-free survival compared to chlorambucil. While effective, neither treatment had a probability of more than 95 percent of being most effective. These differences were found in relatively young, uncomplicated patients, and the evidence for each treatment contrast was from three or fewer small comparison trials. According to the researchers, chlorambucil-based regimens cost less, are less toxic, and are recommended by current practice guidelines. They still remain a realistic first-line choice for appropriate patients. The study was supported in part by AHRQ (HS18574).
See "Comparative efficacy of first-line therapies for advanced-stage chronic lymphocytic leukemia: A multiple-treatment meta-analysis," by Teruhiko Terasawa, M.D., Ph.D., Nikolaos A. Trikalinos, M.D., Benjamin Djulbegovic, M.D., Ph.D., and Thomas A. Trikalinos, M.D., Ph.D., in Cancer Treatment Reviews 39, pp. 340-349, 2013.