ASH News Daily 2017 - Issue 1 - B-55

WARNINGS AND PRECAUTIONS (continued)
* Peripheral Edema was reported with NINLARO. Monitor for fluid retention. Investigate for underlying causes when
appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone per its prescribing
information or NINLARO for Grade 3 or 4 symptoms.
* Cutaneous Reactions: Rash, most commonly maculo-papular and macular rash, was reported with NINLARO. Rash
resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with
supportive care or with dose modification.
* Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury, hepatic 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. Women using hormonal contraceptives should also use a barrier method of contraception.
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 nursing women not to breastfeed during treatment with NINLARO and for 90 days after the last dose.
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 proteasome inhibitor) vs placebo, both in combination with lenalidomide and
dexamethasone, until disease progression or unacceptable toxicity in 722 patients with relapsed and/or refractory
multiple myeloma who received 1-3 prior therapies.1
NE=not evaluable; PFS=progression-free survival.

REFERENCE: 1. Moreau P, Masszi T, Grzasko N, et al; for TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple
myeloma. N Engl J Med. 2016;374(17):1621-1634.

Please see adjacent Brief Summary.
USO/IXA/17/0189

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 1