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Blinatumomab Versus Standard-of-Care
Chemotherapy in Acute Lymphocytic Leukemia
In a multinational, prospective, ran-
domized, phase III study, investigators
found that the anti-CD19/CD3 bispe-
cific T-cell engager antibody blinatu-
momab improved survival outcomes,
compared with standard-of-care che-
motherapy, for patients with relapsed/
refractory, B-cell precursor acute
lymphocytic leukemia (ALL). Treatment
with blinatumomab also led to longer
event-free survival (EFS) and appeared
to lower adjusted rates of serious adverse
events (AEs), according to an article in the
New England Journal of Medicine led by
Hagop Kantarjian, MD, chair of the
Department of Leukemia at the University
of Texas MD Anderson Cancer Center
in Houston, and co-authors.
“Most adults with B-cell precur-
sor ALL will relapse and will die from
complications of resistant disease or as-
sociated treatment,” Dr. Kantarjian and
co-authors explained, adding that “more
effective treatment is needed” for this
patient population.
Patients were enrolled between
January 2014 and September 2015. The
trial included 405 adult patients with
relapsed/refractory, B-cell precursor ALL
that was: refractory to primary induc-
tion therapy or to salvage with intensive
combination chemotherapy; in first
relapse with the first remission lasting
<12 months; in second or greater relapse;
or in relapse at any time after alloge-
neic hematopoietic cell transplantation
(alloHCT). Other criteria included >5
percent bone marrow (BM) blasts and
an Eastern Cooperative Oncology Group
performance status score of ≤2. Patients
were excluded from the trial if they had
other active cancers, had grade ≥2 acute
graft-versus-host disease (GVHD) or
chronic GVHD, or had received HCT or
other active anti-cancer treatment within
4 to 12 weeks prior to randomization.
TABLE 1.
Patients were randomized 2:1 to
receive one of the following:
• blinatumomab administered in
6-week cycles consisting of 4 weeks
of treatment (9 μg/day during
week 1 of induction and 28 μg/day
thereafter) and 2 weeks of no treat-
ment (n=271; mean age = 40.8±17.1
years; range = 18-80 years)
• investigator’s choice of chemotherapy
(n=134; mean age = 41.1±17.3 years;
range = 18-78 years), including:
o fludarabine, high-dose cytosine
arabinoside, and granulocyte
colony-stimulating factor with
or without anthracycline (45%;
n=49)
o a high-dose cytosine arabinoside-
based regimen (17%; n=19)
o a high-dose methotrexate-based
regimen (20%; n=22)
o a clofarabine-based regimen
(17%; n=19)
Protocol-specified therapy could be
discontinued at any time after the first
treatment cycle and the patient could
subsequently undergo HCT if the in-
vestigator determined that such actions
were in the patient’s best interest.
Patients in morphologic remission
(≤5% BM blasts) also received up to
three cycles of consolidation therapy,
and those who were in continued
morphologic remission received up to
12 months of maintenance therapy. In
the blinatumomab group, maintenance
therapy consisted of a 4-week continu-
ous infusion every 12 weeks, and all
patients received dexamethasone prior
to blinatumomab dosing to prevent
infusion reactions.
Most patients (n=376) received at
least one treatment dose. At data cutoff
(January 4, 2016), 22 patients (8%) in
the blinatumomab cohort and zero in
the chemotherapy group were still on
treatment. The median number of treat-
ment cycles was two (range = 1-9 cycles)
for those in the blinatumomab cohort
and one (range = 1-4 cycles) in the che-
motherapy cohort. A total of 251 deaths
were reported.
Investigators found that overall
survival (OS; primary endpoint) was
significantly longer with blinatumomab
(median OS = 7.7 vs. 4.0 months; hazard
ratio [HR] = 0.71; 95% CI 0.55-0.93;
p=0.01).
EFS was also longer for patients re-
ceiving blinatumomab versus chemother-
apy (6-month estimate = 31% vs. 12%;
HR=0.55; 95% CI 0.43-0.71; p<0.001),
as was the median duration of remission
(7.3 vs. 4.6 months; p values not report-
ed). And remission rates (see TABLE 1 ).
“Patients in the blinatumomab group
who achieved complete remission with
full, partial, or incomplete hematologic
recovery had a higher incidence of re-
sponse with respect to minimal residual
disease (MRD) than did patients in the
chemotherapy group, which highlighted
the depth and quality of remissions
achieved with blinatumomab,” the au-
thors noted.
Twenty-four percent of patients in
both the blinatumomab and chemo-
therapy groups proceeded to alloHCT,
which is “a major goal in this popula-
tion,” the authors noted.
“AEs that occurred in the blina-
tumomab group were consistent
with those reported in previous tri-
als,” the authors noted. Serious AEs
were reported more frequently in the
REFERENCE
Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus
chemotherapy for advanced acute lymphoblastic leukemia. N Engl J
Med. 2017;376:836-47.
Best Hematologic Response Within 12 Weeks After Treatment Initiation
Blinatumomab
(n=271) Chemotherapy
(n=134) Treatment Difference (%) p Value
Complete remission with full hematologic
recovery 91; 33.6%
(95% CI 28.0-39.5) 21; 15.7%
(95% CI 10.0-23.0) 17.9
(95% CI 9.6-26.2) <0.001
Complete remission with full, partial, or
incomplete hematologic recovery 119; 43.9%
(95% CI 37.9-50.0) 33; 24.6%
(95% CI 17.6-32.8) 19.3
(95% CI 9.9-28.7) <0.001
Complete remission with partial
hematologic recovery 24; 8.9%
(95% CI 5.8-12.9) 6; 4.5%
(95% CI 1.7-9.5) − −
Complete remission with incomplete
hematologic recovery 4; 1.5%
(95% CI 0.4-3.7) 6; 4