Mark R. Litzow, MD, a professor of Medicine in the Division of Hematology at the Mayo Clinic in Rochester, Minnesota, discusses novel immunologic therapies for the treatment of patients with acute lymphoblastic leukemia (ALL).

These novel therapies possess the ability to treat patients with relapsed/refractory ALL, even those with MRD-positive disease. One of the therapies, the bispecific T-cell-engaging (BiTE) antibody blinatumomab, has demonstrated efficacy in clinical trials. This therapy combines two single-chain variable fragment (scFv) antibodies that are specific to CD3 T cells and CD19 lymphoblasts.

Another promising immunotherapeutic approach in ALL utilizes genetically modified T cells that express chimeric antigen receptors. These therapies are engineered using scFv antitumor antibodies, such as those against CD19. Early evidence suggests these therapies are very effective against ALL, Litzow notes.

Based on promising early evidence, the CAR-modified T cells are being moved toward front-line therapy in order to improve the overall outcomes of both younger and older adults with ALL, Litzow says. â€‹

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Dr. Litzow on New Immunologic Therapies in ALL

Mark R. Litzow, MD, chair, ECOG-ACRIN Leukemia Committee, professor of medicine, Division of Hematology, Mayo Clinic, discusses the role of transplant in patients with acute lymphoblastic leukemia (ALL).

Litzow says the role of transplant in ALL has evolved over the years. The advent of pediatric-intensive chemotherapy regimens has demonstrated improved outcomes in younger patients compared to traditional chemotherapy regimens. Benefit has also been seen in patients up to 40-45 years old, Litzow says, but patients older than 40-45 years did not tolerate the pediatric-intensive chemotherapy regimens as well, due to complications and treatment-related mortality.

These results seem so promising in younger patients that they may not need transplant in first remission. However, younger patients with high-risk features, such as high white blood cell count or adverse cytogenetics, may still benefit from transplant, Litzow says.

Litzow says it is known that outcomes are worse in older patients who undergo chemotherapy treatment. However, reduced-intensity conditioning transplant regimens are in development and have demonstrated encouraging results in older patients. This will allow these patients to get through transplant more easily while more effectively controlling their leukemia, Litzow says.

Mark R. Litzow, MD, chair, ECOG-ACRIN Leukemia Committee, professor of medicine, Division of Hematology, Mayo Clinic, discusses the role of transplant in patients with acute lymphoblastic leukemia

Dr. Litzow on Transplants in Patients with ALL

Mark R. Litzow, MD, chair, ECOG-ACRIN Leukemia Committee, professor of medicine, Division of Hematology, Mayo Clinic, discusses ways of conducting minimal residual disease (MRD) assessments in patients with acute lymphoblastic leukemia (ALL).

Litzow says there are two accepted approaches for MRD assessment: flow cytometry or polymerase chain reaction. Flow cytometry looks for abberant antigen expression of the lymphoblast while polymerase chain reaction looks at T cell receptor gene rearrangements for T cell ALL and hemoglobin gene rearrangements for B cell ALL. The polymerase chain reaction technique is more labor intensive because primers have to be developed for each patient, Litzow says. While the polymerase chain reaction method is slightly more sensitive than flow cytometry, flow cytometry is still an acceptable way to assess MRD.

Currently, next generation sequencing is being tested as a method for assessing MRD. Litzow feels that this will likely become standard practice within the next few years. â€‹

Mark R. Litzow. MD, chair, ECOG-ACRIN Leukemia Committee, professor of medicine, Division of Hematology, Mayo Clinic, discusses ways of conducting minimal residual disease (MRD) assessments in patients with acute lymphoblastic leukemia 

Mark R. Litzow, MD

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Dr. Litzow on New Immunologic Therapies in ALL

Dr. Litzow on Transplants in Patients with ALL

Dr. Litzow on MRD Assessment in ALL