CLINICAL NEWS
treatment cycle, or received obinutuzumab
or bendamustine within two years of the
study’s first treatment cycle.
Patients were randomized 1:1 (stratified based on indolent NHL subtype,
refractory type, number of previous therapies, and geographical region) to receive
one of the following 28-day treatment
cycles:
• obinutuzumab 1,000 mg administered
intravenously (IV) on days 1, 8, and 15
of cycle 1 and day 1 of cycles 2-6, plus
bendamustine 90 mg/m2 on days 1
and 2 of cycles 1-6 (n=194)
• bendamustine 120 mg/m2 on days 1
and 2 of each cycle for up to 6 cycles
(n=202)
“The bendamustine monotherapy group
did not include a maintenance phase
because the cumulative toxicity of bendamustine restricts treatment duration,” Dr.
Sehn and co-authors noted.
Patients in the combination cohort
who did not experience disease progression continued to receive obinutuzumab
1,000 mg maintenance therapy every two
months for two years, or until disease pro-
The first and only oral proteasome inhibitor
• The approval of the NINLARO® (ixazomib) regimen (NINLARO+lenalidomide+dexamethasone)
was based on a statistically significant ~6 month improvement in median progression-free
survival vs the placebo regimen (placebo+lenalidomide+dexamethasone)
— Median PFS: 20.6 vs 14.7 months (95% CI, 17.0-NE and 95% CI, 12.9-17.6, respectively)
- HR=0.74 (95% CI, 0.587-0.939); P=0.012
steatosis, hepatitis cholestatic and hepatotoxicity have
each been reported in < 1% of patients treated with
NINLARO. Events of liver impairment have been reported
(6% in the NINLARO regimen and 5% in the placebo
regimen). Monitor hepatic enzymes regularly during
treatment and adjust dosing as needed.
• Embryo-fetal Toxicity: NINLARO can cause fetal harm.
Women should be advised of the potential risk to a fetus,
to avoid becoming pregnant, and to use contraception
during treatment and for an additional 90 days after the
final dose of NINLARO.
ADVERSE REACTIONS
The most common adverse reactions (≥ 20%) in the
NINLARO regimen and greater than the placebo regimen,
respectively, were diarrhea (42%, 36%), constipation (34%,
25%), thrombocytopenia (78%, 54%; pooled from adverse
events and laboratory data), peripheral neuropathy (28%,
21%), nausea (26%, 21%), peripheral edema (25%, 18%),
vomiting (22%, 11%), and back pain (21%, 16%). Serious
adverse reactions reported in ≥ 2% of patients included
thrombocytopenia (2%) and diarrhea (2%).
SPECIAL POPULATIONS
• Hepatic Impairment: Reduce the NINLARO starting
dose to 3 mg in patients with moderate or severe
hepatic impairment.
• Renal Impairment: Reduce the NINLARO starting dose
to 3 mg in patients with severe renal impairment or
end-stage renal disease requiring dialysis. NINLARO is
not dialyzable.
• Lactation: Advise women to discontinue nursing while
on NINLARO.
DRUG INTERACTIONS: Avoid concomitant administration
of NINLARO with strong CYP3A inducers.
TOURMALINE-MM1: a global, phase 3, randomized (1:1), double-blind,
placebo-controlled study that evaluated the safety and efficacy of
NINLARO (an oral PI) vs placebo, both in combination with lenalidomide
and dexamethasone, until disease progression or unacceptable
toxicity in 722 patients with relapsed and/or refractory MM who
received at least 1 prior therapy.
MM=multiple myeloma; NE=not evaluable; PFS=progression -free
survival; PI=proteasome inhibitor.
Please see adjacent Brief Summary.
USO/IXA/16/0100
ixazomib as a category 1 treatment option for previously treated multiple myeloma.1
gression. Crossover was not allowed prior
to primary analysis.
Clinical examinations, laboratory
evaluations, CT scans, and bone marrow
biopsy sampling (to confirm complete
response) were collected, but positron
emission tomography (PET) scans were
not “because information about the usefulness of PET scans in indolent NHL was
sparse when the study was designed,” the