Written in Blood
Long-Term Survival in ALL after Blinatumomab
Treatment Linked to MRD, T-Cell Expansion
Patients with relapsed/refractory
B-precursor acute lymphocytic
leukemia (ALL) treated with the
bispecific T-cell engager antibody
construct blinatumomab experienced a median overall survival
(OS) of 13 months, with about
one-third of patients alive 30
months after treatment, according
to a long-term follow-up analysis
of an exploratory, dose-finding
phase II study. Those patients with
longer-term survival also all had a
minimal residual disease (MRD)
response, suggesting that MRD response in this disease setting may
translate into clinical benefit.
“The prognosis is poor for
adult patients with relapsed/
refractory B-precursor ALL,”
Gerhard Zugmaier, MD, and
co-authors wrote in their report
of the results. With traditional
chemotherapy approaches, the
median OS is 4.5 to 8.4 months,
and five-year survival rates are
just seven to 10 percent. In a
previous exploratory dose-finding
phase II study in adult patients
with relapsed/refractory B-precursor ALL, treatment with blinatumomab resulted in 69 percent
of patients achieving a complete
response (CR) or CR with partial
hematologic recovery (CRh), and
88 percent of these responders
achieved an MRD response in the
first two treatment cycles.
In the current analysis, Dr.
Zugmaier, from Amgen Research
in Munich, Germany, and colleagues expanded on the previous
study by evaluating clinical characteristics, long-term outcomes
TABLE 5.
of blinatumomab treatment, and
T-cell and B-cell kinetics during
treatment.
The open-label, multicenter,
exploratory, single-arm, phase II
study included 36 adult patients
with relapsed/refractory B-precursor ALL who were treated at nine
centers in Germany between October 6, 2010, and June 19, 2012.
Patient follow-up is ongoing.
Patients were excluded from
the study if they had undergone
autologous hematopoietic cell
transplantation (autoHCT) within
six weeks or allogeneic HCT (alloHCT) within three months before
starting blinatumomab treatment,
had a history or presence of clinically relevant central nervous system (CNS) pathology, active graftversus-host disease (GVHD) and/
or had received immunosuppressive therapy for GVHD within one
week of blinatumomab treatment
start, or had active infections.
Each treatment cycle was six
weeks, with four weeks of continuous intravenous infusion and a
two-week treatment-free interval.
Researchers obtained a bone marrow biopsy before the first cycle of
blinatumomab and again on day
29 of each treatment cycle.
The 36 patients were randomized to three cohorts with the
following dosing schedules:
• Cohort 1 (n=7): blinatumomab 15 μg/m2/day
• Cohort 2a (n=5): blinatumomab 5 μg/m2/day during week
one, then 15 μg/m2/day
• Cohort 2b (n=6): blinatumomab 5 μg/m2/day during
week one, then 15 μg/m2/day
during week two, then 30 μg/
m2/day
• Cohort 3, extension cohort
(n=18): same regimen as cohort 2a
Seventeen patients (47%)
achieved CR with blinatumomab
treatment, defined as:
• ≤5% blasts in the bone marrow
• No evidence of circulating blasts
or extra medullary disease
• Platelets greater than 100,000 μL
• Hemoglobin ≥11 g/dL
• Absolute neutrophil count
(ANC) >1500 μL
Eight patients (22%) achieved
CRh as best response during
treatment.
Patients who