In clinical trials of new medications for chronic myelogenous leukemia, the people enrolled in the study are aged 18 and older, with “older” usually defined as 65 or 70 years. While most people with CML are diagnosed in their early sixties, about one-half are older than 70 years of age. The assumption is that a treatment that is effective in younger people will be as effective for those in their seventies.
However, people in their seventies and eighties are a unique group. Their bodies may not metabolize the drug in the same way, they may have other medical conditions, they may be taking a host of other medications that can interact with the CML drug, and they may be more susceptible to medication-related side effects. All of these factors can have an impact on a drug’s effectiveness in suppressing CML.
Two recent studies have looked at whether TKIs (tyrosine kinase inhibitors) are really as effective in people older than age 75 years. The more recent study looked at 181 people aged 75 to 94 years of age who started taking Gleevec (Breccia and colleagues. Leuk Res 2014;38:1173-1176). About 60% had other medical conditions in addition to their CML. Because of their age and general health, the doctor decided to start with a lower dose of Gleevec about one-third of the time. During the course of treatment, more people with other medical conditions needed to lower their dose of Gleevec compared to people without other medical problems, and they also were twice as likely to stop treatment altogether. However, the reason for stopping didn’t appear to be due to bad reactions to the drug. Sicker individuals were generally less likely to experience severe side effects – which is likely due to the lower doses that were used.
These added factors of illness and dose adjustments didn’t have much impact on the effectiveness of TKI therapy. Most people were able to achieve a complete cytogenetic response (CCyR), although their CCyR rate was somewhat lower compared to those without other medical conditions (54% vs. 66%). However, the burden of other illnesses did weigh more heavily when it came to long-term survival.
A previous report in elderly people with CML had similar results (Latagliata and colleagues. Drugs Aging 2013;30:629-637). In that study, two-thirds were able to start Gleevec at the usual dose, although one-half subsequently needed to take a lower dose or to stop treatment. Overall, 90% achieved a complete hematologic response (i.e. normalization of their white blood cell count) and 64% achieved CCyR. Among those with CCyR, about one-half went on to achieve a major molecular response (MMR). The survival rate at four years was 78% (lower than what’s seen in younger people), but it’s important to note that the cause of death was often due to a medical condition unrelated to CML.
The researchers concluded that there’s no upper age limit for people with CML who need to start treatment with a TKI. People in their seventies, eighties and nineties – including those with other, non-CML medical conditions – can still benefit from CML treatment.