“These three excellent, encouraging, tantalizing studies show that we really are making progress in the treatment of chronic CLL, whereas 10 to 12 years ago, we had no real progress to report,” stated Kanti R. Rai, MD, Chief, CLL Research Program, North Shore-LIJ Medical Center, New Hyde Park, NY.
Idelalisib
The phase I study by Dr. Brown and colleagues showed that idelalisib is unquestionably an attractive drug that was extremely effective in relapsed/refractory poor prognosis patients, he noted.
“The drug achieved a dramatic shrinkage of lymph nodes never before seen after 7 to 8 days of therapy and staying power in lymph node shrinkage, but concern was raised about the increase in blood lymphocyte numbers. This led to the idea to combine idelalisib with rituximab [Rituxan], as was done in the study by Dr. O’Brien and colleagues,” Dr. Rai explained. “The addition of rituximab prevented the rise in lymphocyte count and achieved greater than 50% shrinkage of bulky lymphadenopathy.”
An important aspect of Dr. O’Brien’s trial is the population of older, sicker patients who have been neglected in clinical trials, even though CLL is a disease of the elderly and many have comorbidities, he continued. In this group of patients aged 65 and older, overall response rate was 97% and complete reponse rate was 19%.
“This demonstrated that elderly patients, when given the combination of idelalisib and rituximab, have enormously positive results and tolerable toxicity. The adverse events such as diarrhea and pneumonia suggest that in the future we will have to learn how to use this combination effectively and more safely,” he stated.
Obinutuzumab
The pivotal phase III study of obinutuzumab confirmed that chlorambucil (Leukeran) may be an effective drug if used in combination with a monoclonal antibody, Dr. Rai continued. “In the United States, we have ‘thrown out’ chlorambucil, but the combination with obinutuzumab is extraordinarily more effective and probably more toxic, and we need to learn how to use this combination,” he stated. “Chlorambucil offers hope—not as a single agent, but in combination,” he emphasized.
“I believe we should not be frightened by the toxicity seen with chlorambucil and obinutuzumab. We should go further with this and learn how to use it,” Dr. Rai said.
“With at least 10 new drugs for CLL in the pipeline [including genetically engineered T cells through the introduction of a chimeric antigen receptor, or CART cells], this is a time for optimism, showing us what is next in CLL,” he concluded. ■
Disclosure: Dr. Rai reported no potential conflicts of interest.
