Lloyd Damon, MD, clinical professor, Department of Medicine, University of California, San Francisco (UCSF), director, Hematologic Malignancies and Bone Marrow Transplant, UCSF Robert O. and Angela W. Johnson Endowed Chair in Hematologic Malignancies, UCSF Helen Diller Family Comprehensive Cancer Center, discusses optimal treatment regimens in adolescent/young adult (AYA) acute lymphoblastic leukemia (ALL) . 

AYA ALL was initially defined as patients aged 16 to 21 as these patients had suboptimal 5-year survival rates compared with younger patients and adult patients, says Damon. Now, patients aged 15 to 29 years are considered AYA. Historically, these patients were treated with adult regimens rather than pediatric-inspired regimens, which may have contributed to their poor survival, adds Damon.

Pediatric-inspired regimens are modeled on the Berlin-Frankfurt-Munich regimen, which consists of a myelosuppressive induction treatment, 2 lymphocytotoxic consolidation treatments, followed by myelosuppressive intensification and maintenance therapy. Data from the CALGB 10403 trial showed that a pediatric-inspired regimen was safe and feasible in AYA patients, concludes Damon.

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Lloyd Damon, MD, discusses optimal treatment regimens in adolescent/young adult acute lymphoblastic leukemia.

Dr. Damon on Optimal Treatment Regimens in AYA ALL

Lloyd Damon, MD, director of the Adult Blood and Marrow Transplant and Hematologic Malignancies Program, and chief of the University of California, San Francisco (UCSF) Hematology Clinic, UCSF Helen Diller Family Comprehensive Cancer Center, discusses allogeneic stem cell transplant (ASCT) in the treatment of patients with acute myeloid leukemia (AML).

ASCT remains the standard of care for patients with 

-mutated AML, says Damon, and should be done in every eligible patient. One of the unanswered questions in terms of transplant is whether a FLT3 inhibitor as maintenance after transplant is of value.

A large trial known as BMT CTN 1506/2215-CL-0304 is being conducted in this population. That trial is open to patients at UCSF, notes Damon. Patients with 

-mutated AML in first remission going through allogeneic transplant of any type will then be randomized to 2 years of gilteritinib, another potent and specific FLT3 inhibitor, or placebo, states Damon.

Dr. Damon on Allogeneic Stem Cell Transplant in AML

Lloyd Damon, MD, director of the Adult Blood and Marrow Transplant and Hematologic Malignancies Program, and chief of the University of California, San Francisco (UCSF) Hematology Clinic, UCSF Helen Diller Family Comprehensive Cancer Center, discusses drug development in acute myeloid leukemia (AML).

Venetoclax (Venclexta) has shown activity in almost every hematologic malignancy in which it is tested, explains Damon, including AML. The oral drug is fairly well tolerated and has tremendous activity in older patients in combination with a hypomethylating agent, such as 5-azacytidine (Vidaza) or decitabine. For patients who are ineligible to receive intense inpatient chemotherapy, this may change the standard of care, adds Damon.

In terms of immunotherapy, it has been difficult to identify targets that are differentially expressed. Nonetheless, researchers are looking at CD123 as a potential target because it is differentially expressed on what is considered the leukemic stem cell and underexpressed on the normal hematopoietic stem cell. A number of trials using bispecific T-cell engagers or dual-affinity retargeting as immunotherapy directed against CD123 are now ongoing.

Lloyd Damon, MD

Articles

Dr. Damon on Optimal Treatment Regimens in AYA ALL

Dr. Damon on Allogeneic Stem Cell Transplant in AML

Dr. Damon on Drug Development in AML