Literature Scan
Venetoclax Outperforms Standard Chemo-Immunotherapy
in the Treatment of Relapsed/Refractory CLL
Treatment with the BCL2 inhibitor
venetoclax and rituximab led to deeper
and more durable responses than the
combination of bendamustine and ritux-
imab in patients with relapsed/refractory
chronic lymphocytic leukemia (CLL),
according to results from the phase III
MURANO trial.
“[The venetoclax combination]
showed a significantly higher rate of
progression-free survival (PFS) … than
with a standard chemo-immunotherapy,
with benefit observed in all subgroups
analyzed,” John F. Seymour, MBBS,
PhD, director of cancer medicine and
the Department of Hematology at
Peter MacCallum Cancer Centre in
Melbourne, Australia, and co-authors
reported. Their findings were published
in The New England Journal of Medicine.
The international, randomized,
open-label trial enrolled 389 patients
from 109 sites in 20 countries between
March 31, 2014, and September 23,
2015. Adult patients who received one
to three prior therapies (including at
least one chemotherapy-containing
regimen) were eligible for the study.
Those who previously received
bendamustine could participate if the
response after treatment lasted at least
24 months.
The median patient age was 65 years
(range = 22-85 years), and a major-
ity were men (73.8%). Patients had
the following mutation status: del17p
(n=92/342; 26.9%), TP53 (n=99/376;
26.3%), and IGHV (n=246/360; 68.3%).
Randomization was stratified
according to del17p mutation status,
responsiveness to previous therapy,
and geographic region. All participants
received intravenous (IV) rituximab
375 mg/m 2 on day one of cycle one fol-
lowed by 500 mg/m 2 thereafter for six
cycles, plus either:
• IV bendamustine 70 mg/m 2 on
days 1 and 2 of each 28-day cycle
(n=195)
68 patients (35.1%) had received the full
two years of treatment. In the bendamus-
tine group, 79 percent of patients (n=154)
completed all six treatment cycles, while 34
patients did not. Exposure to rituximab was
similar between the groups, the research-
ers noted.
After a median follow-up of 23.8 months
(range = 0-37.4 months), the median PFS
was not reached in the venetoclax cohort
but was 17 months in the bendamustine
cohort (p<0.001).
Rates of two-year, investigator-assessed
PFS (primary endpoint) were higher in the
venetoclax group: 84.9 percent versus 36.3
myPKFiT ™ for ADVATE ®
[Antihemophilic Factor
(Recombinant)]
The FIRST AND ONLY FDA-cleared PK dosing
software for patients 16 and over with hemophilia A
myPKFiT SOFTWARE HELPS YOU:
SIMPLIFY
the process of PK testing
and data analysis* 1,2
PERSONALIZE
treatment plans for
your patients 1
EDUCATE
your patients using the
reporting capability 1,3
*2 blood draws compared to ISTH 9-11 blood draws 1,4
ADVATE dosing personalized just for him 1
• venetoclax administered via a
5-week ramp-up schedule, from
20 mg per day to 400 mg per day
(n=194)
After completing the ramp-up period,
patients continued venetoclax 400 mg
as monotherapy for up to two years or
until disease progression or unaccept-
able toxicity. Crossover between groups
was not permitted.
By May 8, 2017 (data cutoff), 78
patients (40.2%) in the venetoclax
cohort were still receiving therapy, and
44
ASH Clinical News
myPKFiT for ADVATE helps you make personalized PK-guided prophylaxis a reality in your practice