Michael Keating, MD, BS of MD Anderson Cancer Center, Houston, TX discusses challenges in chronic lymphocytic leukemia (CLL) at the 2016 International Workshop of the German CLL Study Group (GCLLSG) held in Cologne, Germany. Prof. Keating explains that one of the problems in CLL is that it tends to occur in older people and there is always the risk of having some genetic abnormality occur which turns a relatively slow growing disease into a rapidly growing disease. Our treatment of this Richter’s transformation is not very good. Treatment can reduce amount of disease to get patients ready for a stem cell transplant but this is not well tolerated by older patients. Unless you can get to the point where a stem cell transplant is possible, Richter’s is fatal. This is therefore a complication that doctors fear because it can’t be dealt with. The other problematic complication is acute leukemia. Both of these complications tends to occur in about 5% of the patients that get treated with the present chemoimmunotherapy programs, such as FCR. Therefore, there has been a tendency to get away from the chemotherapy drugs which damage DNA and impair the immune system. However, the question that is now coming up is if the same problem will occur with targeted therapy as we have in the present standard therapy.