Acute lymphocytic leukemia (ALL) is a kind of
blood and bone marrow malignancy. Blood cells are generated in the spongy
tissue inside the bones. Acute lymphocytic leukemia gets its name from the fact
that it advances quickly and produces immature blood cells rather than mature
ones.
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.
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, 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.
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. 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.
Treatment Overview
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 years (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.
Reference:
DR. MARK LITZOW et al, ECOG-ACRIN CANCER
RESEARCH GROUP American Society of Hematology (ASH) Annual Meeting and
Exposition