December 31, 2015 | by Letisia Marquez
Leukemia is not one disease, but many individual diseases – and in 2016, treatments will increasingly target the specific types.
Here, Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and leader of the Hematologic Malignancies and Stem Cell Transplantation Institute, and Guido Marcucci, M.D., professor, Department of Hematology & Hematopoietic Cell Transplantation and director of the Gehr Family Center for Leukemia Research, share their insights on research and treatment advances anticipated in 2016.
1. What treatment advances do you expect for leukemia in 2016?
“For acute leukemia in 2016, we anticipate seeing more targeted therapies that are more specific to the leukemia type,” Forman said. “This includes immunotherapy, antibodies and immunoconjugates, which are antibodies that are attached to drugs, and molecularly-targeted small molecules – all of which will be specific to certain types of leukemia.”
Among immunoconjugates, for example, SGN-CD33A has shown significant success in acute myeloid leukemia (AML) in trials at City of Hope. SGN-CD33A is a monoclonal antibody that kills AML cells by first recognizing and latching onto CD33, which studs the surface of most AML tumor cells. Once locked on, the antibody drags a tethered cell-killing drug inside the cancer cell.
Anthony Stein, M.D., director of the Leukemia Program at City of Hope and clinical co-director of the Gehr Family Center for Leukemia Research, led the City of Hope arm of the initial studies of the drug. More trials are ongoing.
Both Forman and Marcucci pointed out that Stein also led research at City of Hope that resulted in the use of the new drug blinatumomab as a therapy for acute lymphoblastic leukemia (ALL). Also a monoclonal antibody drug, blinatumomab has saved many lives in people with advanced ALL.
Said Forman, “The question now is, if we use the drug in people diagnosed with early ALL, will that improve the cure rate? Clinical trials using blinatumomab are moving in that direction.”
And, of course, CAR-T cell therapy will continue to advance the treatment of blood cancers. City of Hope will introduce additional clinical trials of the therapy in 2016, assessing its effectiveness against various hematologic cancers. Last year, the institution launched a T cell therapy clinical trial for ALL, and in 2016, such a trial for AML will also start.
In addition, several molecularly-targeted small molecules are making their way to clinical trials, Marcucci said. Among them, AG120 and AG221 are two molecules, known as inhibitors, which are particularly effective against mutated genes called IDH1 and IDH2. These are mutant proteins that can be present and grow uncontrollably in AML and other types of blood malignancies.
“At City of Hope, studies that combine these inhibitors with chemotherapy will soon be available to patients presenting with IDH1 and IDH2 gene mutations through clinical trials,” he added.
2. How significant are these treatments for the overall field?
“New drugs for the treatment of acute leukemia have not been approved in a long time, so these are exciting developments,” Forman said. “We hope that these trials will ultimately heal patients and lead to FDA approval of more potent drugs to treat leukemia patients, particularly those who are resistant to current therapies or have relapsed. These are potential openings that could have an impact on people’s lives and change how we treat the disease.”
Marcucci said “personalized medicine” – treatment that targets a person’s specific disease -- is also the wave of the future.
“Understanding how and why leukemia cells develop and grow is the basis for developing more effective drugs,” he added. “Each leukemia patient has molecular combinations that are specific to his or her disease, therefore, in the very near future, we hope to move away from the ‘one-therapy-fits-all’ approach and implement personalized medicine.”
That means doctors will chose drug combinations that target a person’s specific leukemia – and the molecular changes taking place – in order to stop the cancer from growing.
3. How will this improve the patient experience or patient outcomes?
“In acute leukemia, the goal is to achieve remission and stay in remission, so the hope is for all these various therapies to help with that,” Forman said. “Novel transplant approaches are also being developed for those patients who need additional therapies to help make the procedure more successful.”
These emerging treatments are also designed to reduce side effects, Marcucci said.
“The hope is that patients will experience less immediate and long-term side effects once they are cured of their disease,” Marcucci said.
4. What research progress do you expect in 2016?
“In 2016, along with clinical trials, we will continue to pursue laboratory-based research that unveils how leukemia changes normal cells and targets these mutations with novel drugs,” Marcucci said. “At City of Hope, we are in a very unique position to not only design new drugs but also to scale-up their production and bring them to clinical trials should any of them show significant anti-leukemia activity and less side effects.”
For some people, City of Hope’s clinical trials are much better options than standard therapy, Forman noted.
In addition, physicians everywhere are hoping for more FDA approvals of therapies that show success in clinical trials.
“We can use those therapies at City of Hope, and, because of our reputation as leaders in leukemia treatment, doctors worldwide will follow our lead,” Forman said.
Learn more about City of Hope's leukemia program and research. If you are looking for a second opinion or consultation about your treatment, request an appointment online or contact us at 800-826-HOPE. Please visit Making Your First Appointment for more information.