Press Release: Practice-changing trial results for acute lymphoblastic leukemia (ALL)

New Orleans, December 13, 2022 — Late-breaking research reveals a major treatment advance for adults with newly diagnosed B lineage acute lymphoblastic leukemia (ALL). The randomized phase 3 study E1910 evaluated blinatumomab immunotherapy in patients with a good prognosis after an initial round of chemotherapy. After about 3.5 years of follow-up, 83% of the patients who went on to receive additional standard consolidation chemotherapy plus experimental blinatumomab were alive versus 65% of those who received chemotherapy only.

Lead researcher Mark R. Litzow, MD (pictured), presented the results of Abstract LBA-1 at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition on Tuesday, December 13, 2022, at 9:00 AM Central Time. LBA-1 was the first of only six late-breaking abstracts at this meeting and was part of the official press program on Monday, December 12, at 8:30 AM CT.

"The addition of blinatumomab to consolidation chemotherapy represents a new standard of care for patients with newly diagnosed B lineage acute lymphoblastic leukemia, who are in remission and have no measurable residual disease after induction chemotherapy," said Dr. Litzow, a Professor of Medicine at the Mayo Clinic in Rochester, Minnesota.

Current treatments for newly-diagnosed ALL frequently lead to remission. Still, unfortunately, relapses often occur in patients, leading to poor survival rates even in those with no measurable residual disease (MRD) after induction chemotherapy. An MRD test looks for any cancer cells that were not killed by cancer treatments.

The goal of the E1910 trial was to further improve overall survival in patients with a better prognosis, defined as in complete remission and MRD negative (<0.01%), by bringing blinatumomab into the front-line setting. E1910 data will be discussed with regulatory agencies for registrational purposes and blinatumomab label expansion.

Blinatumomab is a "targeted" drug that directs a patient's T cells (part of the immune system) to recognize malignant B cells and destroy them. It has two FDA approvals for patients with B lineage ALL: those with relapsed/refractory disease (approved in 2014) and those in first or second complete remission who test positive for MRD at >0.01% (approved 2018).

”This is the first randomized trial to demonstrate that we are able to improve the survival of ALL patients who are in complete remission, including by sensitive MRD testing, and establishes the addition of blinatumomab immunotherapy to standard consolidation chemotherapy as the new standard of care,” said Selina M. Luger MD, FRCPC (pictured). Dr. Luger is Chair of the ECOG ACRIN Leukemia Committee and a Professor of Medicine at the University of Pennsylvania’s Abramson Cancer Center in Philadelphia.

Study E1910 was designed and conducted independently from industry with public funding. The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) led the trial with funding from the National Cancer Institute (NCI), part of the National Institutes of Health. Other NCI-funded network groups participated in the trial.

A total of 77 clinical sites in the United States, Canada, and Israel enrolled 488 patients with newly diagnosed B lineage ALL between December 2013 and October 2019. Patients with the BCR::ABL1 gene abnormality were not eligible. The median age was 51 years (range 30-70).

The standard treatment of ALL is rather complicated, with multiple cycles of combinations of chemotherapy. The E1910 treatment overview is as follows:

• Step 1 Induction – All participants received 2.5 months of combination chemotherapy, including pegaspargase for those under age 55. Patients who tested positive for the B-lymphocyte antigen CD20 also received rituximab. At the end of induction, 395 patients (81%) were in remission, and 333 moved on to Step 2. The rest went off the study.
• Step 2 Intensification – Patients received a course of therapy to stop leukemia from developing in the central nervous system, a common site of relapse if not prevented. Then, all patients were tested centrally for MRD. While the primary evaluation was in the MRD- cohort, MRD+ patients continued in the trial.
• Step 3 Experimental – 286 patients (224 MRD- and 62 MRD+) were randomized/assigned to receive four cycles of consolidation chemotherapy with or without blinatumomab. Blinatumomab was given by continuous intravenous infusion for 4 weeks for each of the four cycles where it was provided. 72% of patients received blinatumomab by 72-and 96-hour infusions, which overcame feasibility issues for conducting the trial. Following FDA approval of blinatumomab for MRD+ patients in March 2018, MRD+ participants were assigned to the blinatumomab arm. MRD- patients continued to be randomized.
• Step 4 Maintenance – Patients received POMP therapy (Purinethol + Oncovin® + methotrexate + prednisone) for about 2 years, commonly given to keep ALL in remission and increase the chance of achieving a cure.

Results

A planned interim analysis showed that among the 224 MRD- patients, there were 56 deaths: 17 in the chemotherapy plus blinatumomab arm and 39 in the control chemotherapy arm. The median follow-up at the time was 43 months. Median overall survival was not reached in the chemotherapy plus blinatumomab arm versus nearly 6 ye¬ars (71.4 months) in the control arm. The trial continues to follow participants.

The study found no new safety concerns associated with the use of chemotherapy plus blinatumomab, and used 72- and 96-hour infusions in 72% of the patients. These infusion times proved necessary to feasibly conduct the trial. The researchers plan to further analyze the data to determine whether particular subgroups of patients are more likely to benefit from blinatumomab than others.

Abstract LBA-1 – Consolidation Therapy with Blinatumomab Improves Overall Survival in Newly Diagnosed Adult Patients with B lineage Acute Lymphoblastic Leukemia in Measurable Residual Disease Negative Remission: Results from the ECOG-ACRIN E1910 Randomized Phase III National Cooperative Clinical Trials Network Trial.

ClinicalTrials.gov Identifier: NCT02003222.

Amgen, the manufacturer of blinatumomab, provided the drug and support through a Cooperative Research and Development Agreement with the NCI.

About ALL

Acute lymphoblastic leukemia (also called acute lymphocytic leukemia) starts in the bone marrow, where blood cells are made. ALL develops from early forms of lymphocytes, a type of white blood cell. The leukemia cells tend to invade the blood quickly, so if not treated, ALL can develop into a fatal disease within months.

About the MRD Assay

The ECOG-ACRIN Leukemia Translational Science Laboratory and its then-director, Elisabeth Paietta, PhD, assessed MRD centrally by standard 6-color flow cytometry. Dr. Paietta went to great lengths to standardize the MRD assay and then carry it out in the E1910 patients.

About ECOG-ACRIN

The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. ECOG-ACRIN comprises nearly 1300 member institutions and 15,000 research professionals in the United States and around the world. Visit ecog-acrin.org, follow us on Twitter @eaonc, Facebook, and LinkedIn, or call 215.789.3631.

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