CLLにおいて経口薬が生存に関する有益性を示した（Abstract: LBA7008）

Early findings from the phase III RESONATE study indicate that ibrutinib yields lasting tumor responses and marked improvement in survival over standard ofatumumab for patients with relapsed chronic lymphocytic leukemia (CLL). This is the first time an oral drug has demonstrated a survival improvement over standard therapy in relapsed CLL. Just as important, the therapy was well tolerated by patients, causing few serious side effects.

CLL is the most common form of leukemia in adults. The standard treatment for CLL is chemo-immunotherapy, a combination of intensive chemotherapy and an antibody such as rituximab. However, elderly patients, who account for the majority of patients with CLL, often cannot tolerate intensive chemotherapy. Ofatumumab is an alternative option for such patients, but studies have shown it is much less effective than intensive chemotherapy.

"With ibrutinib, about 80 percent of patients were still in remission at one year, twice as many as we would expect with standard therapy," said lead study author John Byrd, MD, a professor of medicine at The Ohio State University Comprehensive Cancer Center in Columbus, Ohio. "Although the follow-up was short in this study, the data definitely support the use of ibrutinib before anything else in this setting."

In the study, 391 patients with relapsed or refractory CLL or small lymphocytic lymphoma that had progressed after two or more prior therapies were randomly assigned to treatment with ofatumumab or ibrutinib. The median patient age was 67 years, and 40 percent were older than 70 years.

At a median follow-up of 9.4 months, the response rates were dramatically higher in the ibrutinib arm compared to the ofatumumab arm (42 percent vs. 4 percent). An additional 20 percent of patients treated with ibrutinib had a partial response with persistent lymphocytosis. Ibrutinib was associated with an 80 percent lower risk of disease progression and a 57 percent lower risk of dying compared to ofatumumab; the median progression-free and overall survival have not been reached. Ibrutinib had similarly high activity in two very high-risk groups of patients (17p deletions and purine analog refractory).

Based on these striking early results, patients in the ofatumumab arm were offered the opportunity to cross over to the ibrutinib arm, and patient follow-up continues. According to the researchers, the median overall survival is expected to be in the range of several years.

Overall, both ibrutinib and ofatumumab were well tolerated. Diarrhea, minor bleeding, and atrial fibrillation were more common in the ibrutinib arm, whereas peripheral neuropathy was more common in the ofatumumab arm. This study alleviated concerns about kidney problems that were raised in the phase II ibrutinib study.

"This phase III study in relapsed refractory chronic lymphocytic leukemia confirms that ibrutinib, administered orally, has significant efficacy and is well-tolerated," said Olatoyosi Odenike, MD, ASCO Expert. "These results provide a compelling new treatment option for patients with chronic lymphocytic leukemia, including older adults with this disease, and will significantly change practice."

This research was supported by Pharmacyclics.