Research led by scientists from Cologne University, Amsterdam UMC and Copenhagen University has shown that a chemo free drug combination therapy can yield better results as well as fewer side effects for young people suffering from chronic lymphocytic leukemia (CLL).
CLL is a cancer of the blood and bone marrow leading to abnormal B cell lymphocytes accumulating throughout the body and forcing out healthy cells. The lack of functional B cells often leads to serious infections in people suffering from the incurable disease. While maintenance chemoimmunotherapy is considered the most effective treatment for young people with CLL, its high costs and severe side effects can further complicate the lives of patients.
In the largest CLL study to date, published in The New England Journal of Medicine, researchers have now compared the effects of chemoimmunotherapy with a chemo free combination therapy – a small molecule inhibitor drug called venetoclax combined with an anti-CD20 antibody (either rituximab or obinutuzumab). Venetoclax works by inhibiting a protein called Bcl-2 which normally allows the abnormal cells to proliferate.
“Just like a Formula 1 car on the track, we saw that the CLL cells in the blood are very vulnerable. The protein Bcl-2 protects cells from dying in the blood. This protection gives the cells time to go for a pit stop, just like a Formula 1 car. The pit stop is the lymph node where the cancer cells can recharge and then divide,” explained Arnon Kater, professor of haematology at Amsterdam UMC and chair of the study.
“By combining venetoclax with drugs that can do their job within the pit lane, we thought that combinations were possible that were debilitating and would be more effective than chemotherapy.”
The phase three randomized trial included over 900 young CLL patients from ten different countries. Participants were divided into four groups, receiving either standard chemoimmunotherapy or the venetoclax combination treatment. In all groups, the treatment was temporary compared to previous studies involving continuous treatment which resulted in more side effects and the development of resistance.
According to the researchers, all groups receiving venetoclax had fewer side effects and lower amounts of CLL cells. After three years, the cancer was also two times less likely to return compared to those receiving the standard treatment. Using their experimental drug combination, the scientists were able to show that the therapy could potentially be stopped after a year with patients showing undetectable minimal residual CLL cells. This early endpoint of treatment could save patients from the side effects and costs of maintenance chemoimmunotherapy.
“This study shows that with clever temporary and safe combinations, you can allow patients to be treatment free in the long-term, with a much lower chance of developing resistance. And we also think that it is even possible to stop the combination therapy earlier than after a year. We now want to investigate this,” Kater concluded in a press statement.