Mark R. Litzow, MD, on ALL: Consolidation Therapy With Blinatumomab Improves Overall Survival
2022 ASH Annual Meeting and Exposition
Mark R. Litzow, MD, of the Mayo Clinic, discusses phase III results from the ECOG-ACRIN E1910 Trial, which show that adding blinatumomab to consolidation chemotherapy resulted in a significantly better overall survival in adult patients aged 30 to 70 years with newly diagnosed B-lineage acute lymphocytic leukemia (ALL) who were measurable residual disease–negative after receiving intensification chemotherapy. The authors believe this may represent a new standard of care for this population (Abstract LBA-1).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Blinatumomab is a bispecific T-cell engager molecule that's been approved by the Food and Drug Administration for patients with relapsed and refractory B-lineage, acute lymphoblastic leukemia. And then more recently was approved for the treatment of patients who have measurable residual disease or MRD positive acute lymphoblastic leukemia. The aim of our study was to see if adding blinatumomab to chemotherapy had benefit for patients with MRD negative disease, who we overall think have a better prognosis. The design of the trial was to take patients between the ages of 30 and 70 with B-lineage ALL and newly diagnosed, and give them induction chemotherapy, standard chemotherapy, to get them into remission. Patients who achieved a conventional morphologic remission then had a cycle of intensification therapy to provide prophylaxis for their central nervous system. After that treatment, then they had a bone marrow biopsy and we assessed their MRD status by flow cytometry in a centralized lab.
And patients that were MRD negative at that point were then randomized to either get four cycles of consolidation chemotherapy, followed by one to two years of maintenance chemotherapy or get randomized to receive that same four cycles of chemotherapy, but also have four cycles of blinatumomab intertwined with the cycles of chemotherapy. Patients who are randomized to blinatumomab plus chemotherapy, received two monthly cycles of blinatumomab, recall that that's given by continuous infusion for four weeks. They then got several more cycles of the consolidation chemotherapy, then got another cycle of blinatumomab, then the fourth cycle of consolidation chemotherapy, and then another cycle of blinatumomab, and then went on to maintenance therapy.
And the goal of the study was to see if we could improve their overall survival. We enrolled 488 patients in the trial. 81% of those patients achieved a conventional morphologic complete remission. Some of them unfortunately relapsed shortly after that or had to be taken off study because of toxicity. But at the randomization for the MRD negative patients, we were able to randomize 224 patients, so 112 patients to each of the two arms, the chemotherapy alone or the chemotherapy plus blinatumomab.
And what we found was that the survival was much improved with blinatumomab and chemotherapy arm. And this was based on less relapses in that arm. Even though these patients are MRD negative, we know that they can still relapse and could still have residual disease. At three and a half years of follow up, the survival in blinatumomab plus chemotherapy arm was 83% versus 65% in the patients who got chemotherapy, and this was from the time of randomization.
We also showed a benefit for relapse-free survival as well. We're very excited about these results. We think they represent a new standard of care and that blinatumomab should be considered to be added to consolidation chemotherapy for patients for standard of care. We are discussing now how to build on these studies. We think that adding blinatumomab earlier in the treatment course may be beneficial, and there are studies that are beginning to look at that. We're also incorporating this into the other new modalities of therapy that you all are aware of, that are involved in the treatment of B-lineage ALL.
Elias Jabbour, MD, of The University of Texas MD Anderson Cancer Center, discusses an analysis confirming that olverembatinib is a potentially viable treatment option for patients with chronic myeloid leukemia (CML) and Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL), including those with CML whose disease did not respond to ponatinib or asciminib, or who had a T315I mutation (Abstract 82).
Jiye Liu, PhD, of Dana-Farber Cancer Institute, discusses study findings that demonstrate KDM6A regulates CD38 and CD48 expression in multiple myeloma. Dr. Liu’s team validated combination treatment with an FDA-approved EZH2 inhibitor plus daratumumab, which can overcome daratumumab resistance in preclinical multiple myeloma models, providing the rationale for combination clinical trials to improve patient outcome (Abstract 148).
Abdul Rahman Al Armashi, MD, of Seidman Cancer Center, Case Western University, University Hospitals Cleveland Medical Center, discusses a retrospective analysis, using a CDC database, in one of the largest subgroup-based racial population studies analyzing mortality trends in patients with acute myeloid leukemia (AML). Between 2000 and 2019, AML mortality was the highest in Whites and the lowest in American Indians or Alaska Natives. The highest rate of increase in mortality was seen in Asians or Pacific Islanders. Dr. Al Armashi talks about the many variables that might contribute to these inequalities (Abstract 600).
Eileen M. Boyle, MD, PhD, of the Perlmutter Cancer Center, NYU Langone Health, discusses Fc-mediated antibody effector function, inflammation resolution, and oligoclonality and their role in predicting sustained measurable residual disease negativity in patients with newly diagnosed multiple myeloma who were treated with immunotherapy regimens. For the first time, an analysis of T-cell receptors shows that oligoclonal profiles seen on treatment may influence the fitness of the immune response (Abstract 100).
Tycel J. Phillips, MD, of the City of Hope National Medical Center, discusses data that showed fixed-duration glofitamab monotherapy induced high and durable complete response rates in patients with mantle cell lymphoma (MCL) who received obinutuzumab pretreatment. This is one of the largest data sets and longest follow-ups reported with a CD20/CD3 bispecific monoclonal antibody for patients with relapsed or refractory MCL (Abstract 74).