Major progress against chronic lymphocytic leukemia (CLL), led by scientists and physicians at MD Anderson, has pushed this most common adult leukemia near the brink of elimination.
MD Anderson’s Moon Shots Program is poised to lead the final push by addressing CLL resistance to impressive new targeted therapies, launching innovative combination clinical trials and applying immunotherapy to find and kill cells that survive initial treatment.
CLL produces defective white blood cells, or lymphocytes, which fight infections and disease. Over time, the malignant B cells accumulate in the blood and bone marrow, crowding out healthy blood cells.
Combination chemotherapy and antibody treatment effectively attack CLL in many patients.
MD Anderson has been at the forefront for decades in understanding how different drugs work together. The MD Anderson team developed the FCR regimen, currently considered standard-of-care therapy, which might cure up to one-third of CLL patients who need therapy.
Success comes with a price for some; treatments can further suppress the immune system, making patients more susceptible to infection and sometimes second cancer. Targeted therapies are less harsh and more specific than chemotherapy, and the CLL Moon Shot is studying how to best use these new, targeted therapies.
Understanding breakthrough drugs and extending their reach
The CLL Moon Shot team is actively studying a breakthrough class of drugs which block proteins that connect with the B cell receptor, thwarting critical signaling in the malignant B cells. These experimental drugs prevent CLL cell signaling with dramatic effect on leukemic cells but little impact on other cells.
CLL cells hide and are protected from chemotherapy in niches, such as the lymph nodes. The new B cell signaling inhibitors force these cells out from hiding and into circulation, where they are more vulnerable to attack by the treatment including chemotherapy.
MD Anderson investigators led initial trials of these drugs and are now leading studies looking at combinations and rates of cell birth and death. Several labs in the moon shot are studying samples from these trials to better understand how exactly these drugs work to treat CLL.
A new 200-patient clinical trial tests one B cell signaling inhibitor ibrutinib, with or without a proven antibody effective in CLL, to further understand the way both drugs work against CLL. This trial also addresses another goal: evaluating how the CLL cells behave and change before and after treatment.
Samples from patients enrolled in this and other clinical trials will help the moon shots team conduct future research to address new questions.
Immunotherapy to wipe out residual CLL
One moon shot project develops immunotherapy to hunt down remaining CLL cells and destroy them.
MD Anderson researchers have developed a way to train T cells, the attack cells of the immune system, to recognize and specifically kill only leukemia cells. This involves taking some of a patient’s T cells and transferring genetic material to produce a chimeric antigen receptor (CAR). The T cells are trained to seek out a specific molecule and destroy the cell to which the target molecule is attached.
The idea is to treat first with combination therapy to kill the vast majority of CLL and then follow with immune therapy to mop up the remaining cells. The immune therapy also, in effect, would vaccinate against CLL, so the immune system will recognize any new cells and prevent rebirth of the disease.
Massive collaboration to bring such great scientific and clinical expertise to bear is not the type of project funded from traditional research sources. At this stage of the Moon Shots Program, philanthropy is crucial to progress. In the case of CLL, donor support may push this leukemia past its tipping point on the road to elimination.
The moon shot leaders have galvanized a large and integrated team that is moving forward in a milestone-driven manner to convert scientific knowledge into drugs, tests, devices and policies that can benefit patients as quickly as possible.
Marion Meyer was diagnosed with an aggressive form of chronic lymphocytic leukemia (CLL) in 2002 and given three years to live. At age 59, with three children and seven grandchildren, she determined it was not her time to die. An out-of-state patient, Marion promised herself to get a second opinion, no matter the distance. The former biochemist searched for the doctor who had done the most research on her disease and found MD Anderson's Michael Keating, M.D., professor in Leukemia and co-leader of the CLL Moon Shot. She says, “I chose MD Anderson because life is worth the distance.” Continue reading...