Mark R. Litzow, MD

Mark R. Litzow, MD, chair and professor of medicine in the division of hematology at the Mayo Clinic, discusses the purpose of a trial of blinatumomab (Blincyto) for patients with newly diagnosed B-lineage acute lymphoblastic leukemia (B-ALL).

Blinatumomab is a bispecific T-cell engager approved by the FDA for patients with relapsed/refractory B-ALL and patients who are positive for measurable residual disease (MRD) with a morphological complete response (CR). Patients who respond to chemotherapy may still have relapsed disease even after displaying MRD-negative status by flow cytometry or molecular testing. Litzow says it has not yet been tested in patients who are MRD negative.

This phase 3 trial (NCT02003222) was designed to assess whether 

 negative patients with B-ALL who have a CR and are MRD negative after chemotherapy have improved outcomes with blinatumomab. Patients were randomly assigned 1:1 after chemotherapy to receive blinatumomab with consolidation chemotherapy or chemotherapy alone. The primary end point was overall survival, and secondary end points included relapse-free survival, MRD status, and incidence of adverse events.

 This was a trial to...see if blinatumomab would improve the outcome of newly diagnosed patients with B-lineage ALL who are 

 negative. Now blinatumomab…is already FDA approved for treatments with relapsed/refractory ALL, and also patients [who] are MRD-positive. So MRD can be measured by flow cytometry and also by molecular means. It's not been tested yet in patients who are MRD negative, so we didn't know whether it would be a benefit to those patients. We know those patients have a better prognosis overall than the MRD-positive patients. But they still relapse during the course of their treatment and after, so we know that they still have some leukemia in their system even though they're MRD negative. We wanted to add blinatumomab to chemotherapy in that group to see if we can improve their outcome.

Videos

Mark R. Litzow, MD, discusses the purpose of a trial of blinatumomab for patients with newly diagnosed B-lineage acute lymphoblastic leukemia. 

Rationale for a Trial of Blinatumomab in MRD-Negative ALL

Mark R. Litzow, MD, chair, professor of medicine, Division of Hematology, Mayo Clinic, discusses the talk he gave on initial treatment options for patients with acute lymphoblastic leukemia (ALL) during the National Comprehensive Cancer Network 2022 Annual Congress: Hematologic Malignancies.

After years of little to no new developments in the ALL space, experts have discovered that young adults up to the age of 40 with ALL can tolerate pediatric treatment regimens. When providing patients with additional doses of these agents, better survival outcomes have been observed.

As a result of young adult and pediatric patients being able to tolerate these intensive regimens, they are now beginning to be incorporated into treatment for this patient population.

I focused in my talk about initial treatment options for patients with acute lymphoblastic leukemia and risk stratification. Some of the new developments in ALL, and there have been many that have been very exciting for us after many years of stagnation where we did not have a lot of new treatments, one of the important things we learned is that in younger adults with ALL, they can tolerate treatment programs that have been used in children, so pediatric regimens. These regimens contain more drugs like vincristine, asparaginase, and corticosteroids.


It seems that additional doses of those drugs have helped improve the outcomes in children and now we have found in young adults. Young adults include patients up to 40 and in some circumstances, up to 50 or 55. They can tolerate these intensive regimens and we see better outcomes, so better survival, and less relapse. We have been incorporating those types of regimens into the treatment of younger patients with acute lymphoblastic leukemia.

Mark R. Litzow, MD, discusses the talk he gave on initial treatment options for patients with acute lymphoblastic leukemia during the National Comprehensive Cancer Network 2022 Annual Congress: Hematologic Malignancies.


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Incorporating Pediatric Regimens in the Treatment of 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).

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, but patients older than 40-45 years did not tolerate the pediatric-intensive chemotherapy regimens as well due to complications and treatment-related mortality

Due to these results, younger patients may not need transplants in first remission but younger patients with high-risk features, such as high white blood cell count or adverse cytogenetics, may still benefit from transplant

Outcomes are worse in older patients who undergo chemotherapy treatment, but reduced-intensity conditioning transplant regimens are in development and have demonstrated encouraging results in older patients

The Role of 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).

Flow cytometry looks for abberant antigen expression of the lymphoblast

Polymerase chain reaction looks at T cell receptor gene rearrangements for T cell ALL and hemoglobin gene rearrangements for B cell ALL

Polymerase chain reaction is more labor intensive than flow cytometry, as primers have to be developed for each patient

Next generation sequencing is being tested as a method for assessing MRD

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 ALL.

Mark R. Litzow, MD | Authors

Articles

Rationale for a Trial of Blinatumomab in MRD-Negative ALL

Incorporating Pediatric Regimens in the Treatment of ALL

The Role of Transplants in Patients With ALL

Assessing Minimal Residual Disease in Patients With ALL