ASH Clinical News July 2016 | Page 38

Literature Scan

PE and the benefit of screening for
VTE in certain SVT patients.
“SVT has long been considered
a benign entity, with more local
than systemic implications,” Dr. Di
Minno and authors wrote, “[and]
SVT may be a manifestation of a
systemic tendency to thrombosis.”
In this systematic literature
review and meta-analysis, Dr. Di

Minno and authors selected 22
studies (comprising a total of 4,379
patients with lower-limb SVT and
concomitant DVT/PE). Case reports, reviews, and animal studies
were excluded from the analysis.
Results from the included
studies were stratified based on
the study design (prospective
[n=15] vs. retrospective [n=7]).

Twenty-one studies reported on
the prevalence of DVT (n=4,358)
and 11 (n=2,484) reported on the
prevalence of PE.
The number of patients included in each study ranged from five
to 844, the mean age ranged from
47 to 79 years, and the percent of
female patients ranged from 47.6
percent to 80 percent. An ac-

tive malignancy was reported in
zero to 18.3 percent of patients,
obesity in 16.2 to 35.8 percent,
recent surgery in 3.7 to 30 percent,
trauma in zero to 13.4 percent, and
pregnancy in zero to 11.9 percent.
Among the 21 studies examining DVT, the pooled weighted
mean prevalence of concomitant
DVT at SVT diagnosis was 18.1

REFERENCE: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for
Multiple Myeloma V.3.2016. © National Comprehensive Cancer Network, Inc 2016. All rights reserved. Accessed April 5, 2016.
To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE
CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all otherT:7”
NCCN Content are trademarks owned by the National
Comprehensive Cancer Network, Inc.

BRIEF SUMMARY OF PRESCRIBING INFORMATION
NINLARO (ixazomib) capsules, for oral use

IXAZ15CDNY3359_NINLARO_HCP_Brief_Summary_FINAL_r8.indd 1

3/25/16 3:11 PM

T:10”

1 INDICATION
rabbits at doses resulting in exposures that were slightly higher than those
NINLARO (ixazomib) is indicated in combination with lenalidomide and observed in patients receiving the recommended dose.
dexamethasone for the treatment of patients with multiple myeloma who have Females of reproductive potential should be advised to avoid becoming
received at least one prior therapy.
pregnant while being treated with NINLARO. If NINLARO is used during
pregnancy or if the patient becomes pregnant while taking NINLARO, the
5 WARNINGS AND PRECAUTIONS
patient should be apprised of the potential hazard to the fetus. Advise females
5.1 Thrombocytopenia: Thrombocytopenia has been reported with NINLARO
of reproductive potential that they must use effective contraception during
with platelet nadirs typically occurring b etween Days 14-21 of each 28-day cycle
treatment with NINLARO and for 90 days following the final dose.
and recovery to baseline by the start of the next cycle. Three percent of patients
in the NINLARO regimen and 1% of patients in the placebo regimen had a platelet 6 ADVERSE REACTIONS
count ≤ 10,000/mm3 during treatment. Less than 1% of patients in both regimens The following adverse reactions are described in detail in other sections of the
had a platelet count ≤ 5000/mm3 during treatment. Discontinuations due to prescribing information:
thrombocytopenia were similar in both regimens (< 1% of patients in the • Thrombocytopenia [see Warnings and Precautions (5.1)]
NINLARO regimen and 2% of patients in the placebo regimen discontinued one or
• Gastrointestinal Toxicities [see Warnings and Precautions (5.2)]
more of the three drugs). The rate of platelet transfusions was 6% in the NINLARO
• Peripheral Neuropathy [see Warnings and Precautions (5.3)]
regimen and 5% in the placebo regimen.
Monitor platelet counts at least monthly during treatment with NINLARO. • Peripheral Edema [see Warnings and Precautions (5.4)]
Consider more frequent monitoring during the first three cycles. Manage • Cutaneous Reactions [see Warnings and Precautions (5.5)]
thrombocytopenia with dose modifications and platelet transfusions as per • Hepatotoxicity [see Warnings and Precautions (5.6)]
standard medical guidelines.
6.1 CLINICAL TRIALS EXPERIENCE
5.2 Gastrointestinal Toxicities: Diarrhea, constipation, nausea, and vomiting,
Because clinical trials are conducted under widely varying conditions, adverse
have been reported with NINLARO, occasionally requiring use of antidiarrheal
reaction rates observed in the clinical trials of a drug cannot be directly
and antiemetic medications, and supportive care. Diarrhea was reported in
compared to rates in the clinical trials of another drug and may not reflect the
42% of patients in the NINLARO regimen and 36% in the placebo regimen,
rates observed in practice.
constipation in 34% and 25%, respectively, nausea in 26% and 21%,
respectively, and vomiting in 22% and 11%, respectively. Diarrhea resulted in The safety population from the randomized, double-blind, placebo-controlled
discontinuation of one or more of the three drugs in 1% of patients in the clinical study included 720 patients with relapsed and/or refractory multiple
NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing myeloma, who received NINLARO in combination with lenalidomide and
dexamethasone (NINLARO regimen; N=360) or placebo in combination with
for Grade 3 or 4 symptoms.
lenalidomide and dexamethasone (placebo regimen; N=360).
5.3 Peripheral Neuropathy: The majority of peripheral neuropathy adverse
reactions were Grade 1 (18% in the NINLARO regimen and 14% in the placebo The most frequently reported adverse reactions (≥ 20%) in the NINLARO
regimen) and Grade 2 (8% in the NINLARO regimen and 5% in the placebo regimen and greater than the placebo regimen were diarrhea, constipation,
regimen). Grade 3 adverse reactions of peripheral neuropathy were reported at thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting,
and back pain. Serious adverse reactions reported in ≥ 2% of patients included
2% in both regimens; there were no Grade 4 or serious adverse reactions.
thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more
The most commonly reported reaction was peripheral sensory neuropathy
of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.
(19% and 14% in the NINLARO and placebo regimen, respectively). Peripheral
motor neuropathy was not commonly reported in either regimen (< 1%). Table 4: Non-Hematologic Adverse Reactions Occurring in ≥ 5% of Patients
Peripheral neuropathy resulted in discontinuation of one or more of the three with a ≥ 5% Difference Between the NINLARO Regimen and the Placebo
drugs in 1% of patients in both regimens. Patients should be monitored for Regimen (All Grades, Grade 3 and Grade 4)
symptoms of neuropathy. Patients experiencing new or worsening peripheral
NINLARO +
Placebo +
neuropathy may require dose modification.
Lenalidomide and
Lenalidomide and
Dexamethasone
Dexamethasone
5.4 Peripheral Edema: Peripheral edema was reported in 25% and 18% of
N=360
N=360
patients in the NINLARO and placebo regimens, respectively. The majority of
peripheral edema adverse reactions were Grade 1 (16% in the NINLARO
System Organ Class /
N (%)
N (%)
Preferred Term
regimen and 13% in the placebo regimen) and Grade 2 (7% in the NINLARO
regimen and 4% in the placebo regimen).
Grade Grade
Grade Grade
All
All
Grade 3 peripheral edema was reported in 2% and 1% of patients in the
3
4
3
4
NINLARO and placebo regimens, respectively. There was no Grade 4 peripheral
Infections and infestations
edema reported. There were no discontinuations reported due to peripheral
69 (19) 1 (< 1)
0
52 (14) 2 (< 1)
0
Upper respiratory tract
edema. Evaluate for underlying causes and provide supportive care, as
infection
necessary. Adjust dosing of dexamethasone per its prescribing information or
Nervous system disorders
NINLARO for Grade 3 or 4 symptoms.
100 (28)
7 (2)
0
77 (21)
7 (2)
0
Peripheral neuropathies*
5.5 Cutaneous Reactions: Rash was reported in 19% of patients in the
NINLARO regimen and 11% of patients in the placebo regimen. The majority of
Gastrointestinal disorders
the rash adverse reactions were Grade 1 (10% in the NINLARO regimen and
8 (2)
151 (42) 22 (6)
0
130 (36)
0
Diarrhea
7% in the placebo regimen) or Grade 2 (6% in the NINLARO regimen and 3%
122 (34) 1 (< 1)
0
90 (25) 1 (< 1)
0
Constipation
92
(26)
6
(2)
0
74
(21)
0
0
Nausea
in the placebo regimen). Grade 3 rash was reported in 3% of patients in the
79 (22)
4 (1)
0
38 (11) 2 (< 1)
0
Vomiting
NINLARO regimen and 1% of patients in the placebo regimen. There were no
Grade 4 or serious adverse reactions of rash reported. The most common type
Skin and subcutaneous
tissue disorders
of rash reported in both regimens included maculo-papular and macular rash.
68 (19)
9 (3)
0
38 (11)
5 (1)
0
Rash*
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
Musculoskeletal and
modification if Grade 2 or higher.
connective tissue disorders
0
57 (16)
9 (3)
0
74 (21) 2 (< 1)
Back pain
5.6 Hepatotoxicity: Drug-induced liver injury, hepatocellular injury, hepatic
steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in
General disorders and
< 1% of patients treated with NINLARO. Events of liver impairment have been
administration site
conditions
reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor
91 (25)
8 (2)
0
66 (18)
4 (1)
0
Edema peripheral
hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms.
5.7 Embryo-Fetal Toxicity: NINLARO can cause fetal harm when administered Note: Adverse reactions included as preferred terms are based on MedDRA version 16.0.
to a pregnant woman based on the mechanism of action and findings in
*Represents a pooling of preferred terms
animals. There are no adequate and well-controlled studies in pregnant women
using NINLARO. Ixazomib caused embryo-fetal toxicity in pregnant rats and
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