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Inotuzumab ozogamicin proves highly
effective in older patients with relapsed/
refractory acute lymphoblastic leukaemia
Inotuzumab ozogamicin has
been proven highly effective in
older patients with relapsed/
refractory acute lymphoblastic
leukaemia for whom treatment
options are limited, reports the
global, phase 3, randomised,
controlled INO-VATE trial.
E
lias J Jabbour, MD, of the University
of Texas MDAnderson Cancer Center,
Houston, explained that inotuzumab
ozogamicin, an anti-CD22 antibody-
calicheamicin conjugate, has demonstrated
superior response versus standard care for
relapsed/refractory acute lymphoblastic
leukaemia in the ongoing phase 3 INO-VATE
trial (complete remission/complete remission
with incomplete haematologic recovery, 81%
[95% CI 72–88%]; minimal residual disease
negativity in responders, 78% [68–87%];
median remission duration, 4.6 [3.9–5.4]
months).
Dr Jabbour and colleagues set out to assess the
efficacy and safety of inotuzumab ozogamicin
in patients with relapsed/refractory acute
lymphoblastic leukaemia age younger than
55 versus 55 years of age and older.
Per protocol, the intent-to-treat analyses of
complete response/complete response with
incomplete haematologic recovery included the
first 218 of 326 patients randomised (ITT 218).
The safety population included 139 patients
who received at least one inotuzumab
ozogamicin dose (maximum 1.8 mg/m
2
per
cycle [0.8 mg/m
2
on day 1; 0.5 mg/m
2
on days
8 and 15 of a 21–28 day cycle for six cycles
or less]). Minimal residual disease negativity
was assessed by central flow cytometry
(<0.01%). Data as of 2014 were presented,
as the trial is ongoing.
One hundred and nine patients in the ITT 218
received inotuzumab ozogamicin (median age
47 [range, 18–78] years; patients
≥
55 years of
age, 43 [39%]). Remission rates and duration
of response were similar, whereas minimal
residual disease-negativity rates in responders
were numerically higher in older patients.
In the safety population, grade
≥
3 adverse
events were most frequently cytopenias
(neutropenia, 46%; thrombocytopenia, 37%;
febrile neutropenia, 24%). These grade
≥
3
adverse events were more common in patients
≥
55 (n=53) versus <55 years (n=86) of age:
thrombocytopenia (49% vs 29%), neutropenia
(53% vs 42%), febrile neutropenia (28% vs
21%). Patients
≥
55 versus <55 years of age
discontinued due to adverse events at similar
rates (both 17%).
For patients
≥
55 versus <55 years of age,
any-grade hepatobiliary adverse event rates
were similar (both 26%) and included,
hyperbilirubinemia (both 15%), and veno-
occlusive liver disease including post stem
cell transplant veno-occlusive disease (both
11%; two fatal in patients <55 years of age
[one after second stem cell transplant]).
Dr Jabbour concluded that inotuzumab
ozogamicin was proven to be highly effective
in older patients with relapsed/refractory
acute lymphoblastic leukaemia for whom
treatment options are limited. Responses and
safety profiles were similar to those of younger
patients and the overall study population.
Responses and safety
profiles were similar
to those of younger
patients and the overall
study population.
EHA 2016
21
DECEMBER 2016