It has been awhile since we last discussed CLL treatment in the elderly. We consider this a key topic for several reasons. First, the median age of CLL at diagnosis is 72 years, making the elderly the majority of new CLL patients. Second, traditional chemoimmunotherapy regimens are often too aggressive for elderly patients. Physicians must balance their approach based on tolerability and effectiveness. Third, historically clinical trials have excluded the elderly. By definition, most studies consider 65 and older as elderly. We do not believe this definition to be true for most patients, and other elements such as fitness status and presence of other serious medical conditions need to be considered.
The German CLL study group was one of the first groups to look at how elderly patients considered "fit" responded to traditional chemoimmunoptherapy. Their group and others have shown that older patients who are in excellent condition with limited other medical conditions can be treated with fludarabine based regimens, such as fludarabine, cyclophosphamide and rituximab which is the standard of care regimen for younger patients.
Dr. Alessandra Ferrajoli
Other patients, based on age and other health conditions, may require a less aggressive approach. We have told you about a variety of such approaches in the past, but we wanted to update you about the long-term data. Dr. Alessandra Ferrajoli and her colleagues at MD Anderson conducted a clinical trial giving the immune stimulator GMCSF and rituximab in untreated elderly patients. The study improved the response rate of ritxumab alone. After five years of follow-up, over 80% of the patients were still alive.
Dr. Ferrajoli also looked at lenalidomide (Revlimid) in the treatment of elderly CLL. Lenalidomide is an oral immune modulating agent. The research team found 80% of patients treated with this agent remained alive after five years of follow-up.
The GMCSF and lenalidomide studies described above were initiated several years ago and were examples of studies specifically dedicated to treatment for the elderly; it has taken a number of years to determine if the responses were durable. Dr. Ferrajoli's group is now looking at ofatumumab as initial treatment for the elderly.
What about some of the newer studies? Has the situation changed? Are elderly permitted to enroll? We took a look at recent studies with new agents on clinicaltrials.gov. We were pleasantly surprised to find that age was not an exclusion criteria on many studies. However, elderly are more likely to be excluded based on other comorbidities. Gratifyingly, we found several studies specifically designated for the elderly. For example, there is an ibrutinib vs chlorambucil randomized study specifcally for treatment-na´ve patients 65 or older. Several cooperative groups, including the German and British groups, are also looking at less aggressive combinations for the elderly using monoclonal antibodies alone or in combination with chemotherapy. Some of these studies are just getting underway. We will update you as data emerges.