The Chronic Lymphocytic Leukemia (CLL) Moon Shot is accelerating the transition from chemotherapy combinations for most patients to new targeted therapies and immunotherapy approaches.
MD Anderson CLL experts were instrumental in developing the targeted therapies ibrutinib and idelalisib, both approved in 2014 for CLL by the Food and Drug Administration (FDA). These and other drugs such as the antibody rituximab are inducing long-term responses in CLL patients with fewer and less harsh side effects than chemo.
Only 15% of new CLL patients at MD Anderson are treated with chemo, down from 48% two years ago. And that’s by design, says moon shot co-leader Michael Keating, M.D., professor in Leukemia. “We hope to double the cure rate to 70 percent of patients by using these new approaches,” Keating says.
While chemo combinations cure about 35% of patients, they also are unfit for elderly or frail patients, work poorly against CLL with specific mutations, cause development of additional cancers such as AML and MDS, and severely suppress the immune system.
Jan Burger, M.D., Ph.D., leads a 208-patient clinical trial of ibrutinib or ibrutinib plus rituximab. In it, each patient’s CLL is genomically analyzed before and after treatment, as well as after the disease becomes drug-resistant, should that occur. Such specific genomic information will help investigators understand how resistance develops and how to counter it.
The randomized trial opened in December of 2013 and has now enrolled more than 110 patients.
Burger says the hope is the trial will address a puzzle about ibrutinib resistance.
“Ibrutinib generally kills 90 to 95% of CLL cells, leaving detectable levels of the disease in the blood and bone marrow a year or more after treatment, yet the patients have no clinical problems,” he says. There’s a concern that the residual disease will seed a recurrence later.
Other patients respond well initially to ibrutinib and then become fully resistant. “We don’t know if the same mechanisms are involved in both cases,” Burger says.
Additional studies are underway to better illuminate how ibrutinib works and its relation to white blood cells called T cells, the attack dogs of the immune system.