On Location 2018 ASH Annual Meeting
Mikkael Sekeres
Director, Leukemia
Program, Cleveland
Clinic
Cleveland, OH
Danielle Ofri, MD, PhD
Associate Professor,
New York University
School of Medicine
New York, NY
Every Patient Tells a Story:
Using Narrative Medicine to Cure Disease
As part of the Education Program
at the 2018 ASH annual meeting,
three physician-writers will offer
their take on the intersection of
storytelling, writing, and medicine
– asking why doctors should care
about the narrative, how the pa-
tient narrative informs treatment
decisions, and how writing can be
a tool for advocacy and change.
Here, session chair Mikkael
Sekeres, MD, MS (Editor-in-Chief
of ASH Clinical News), and speaker
Danielle Ofri, MD, PhD, discuss
the importance of patient stories
and using narrative to enhance the
doctor-patient relationship.
REVLIMID [lenalidomide] capsules, for oral use
Venous and Arterial Thromboembolism [see Boxed Warning, Warnings
and Precautions (5.4)]
VTE and ATE are increased in patients treated with REVLIMID.
Deep vein thrombosis (DVT) was reported as a serious (7.4%) or
severe (8.2%) adverse drug reaction at a higher rate in the REVLIMID/
dexamethasone group compared to 3.1 % and 3.4% in the placebo/
dexamethasone group, respectively in the 2 studies in patients with at
least 1 prior therapy with discontinuations due to DVT adverse reactions
reported at comparable rates between groups. In the NDMM study, DVT
was reported as an adverse reaction (all grades: 10.3%, 7.2%, 4.1%), as
a serious adverse reaction (3.6%, 2.0%, 1.7%), and as a Grade 3/4
adverse reaction (5.6%, 3.7%, 2.8%) in the Rd Continuous, Rd18, and
MPT Arms, respectively. Discontinuations and dose reductions due to
DVT adverse reactions were reported at comparable rates between the
Rd Continuous and Rd18 Arms (both <1%). Interruption of REVLIMID
treatment due to DVT adverse reactions was reported at comparable
rates between the Rd Continuous (2.3%) and Rd18 (1.5%) arms.
Pulmonary embolism (PE) was reported as a serious adverse drug
reaction (3.7%) or Grade 3/4 (4.0%) at a higher rate in the REVLIMID/
dexamethasone group compared to 0.9% (serious or grade 3/4) in the
placebo/dexamethasone group in the 2 studies in patients with, at least
1 prior therapy, with discontinuations due to PE adverse reactions
reported at comparable rates between groups. In the NDMM study, the
frequency of adverse reactions of PE was similar between the Rd
Continuous, Rd18, and MPT Arms for adverse reactions (all grades:
3.9%, 3.3%, and 4.3%, respectively), serious adverse reactions (3.8%,
2.8%, and 3.7%, respectively), and grade 3/4 adverse reactions (3.8%,
3.0%, and 3.7%, respectively).
Myocardial infarction was reported as a serious (1.7%) or severe (1.7%)
adverse drug reaction at a higher rate in the REVLIMID/dexamethasone
group compared to 0.6 % and 0.6% respectively in the placebo/
dexamethasone group. Discontinuation due to MI (including acute)
adverse reactions was 0.8% in REVLIMID/dexamethasone group and
none in the placebo/dexamethasone group. In the NDMM study,
myocardial infarction (including acute) was reported as an adverse
reaction (all grades: 2.4%, 0.6%, and 1.1%), as a serious adverse
reaction, (2.3%, 0.6%, and 1.1%), or as a severe adverse reaction
(1.9%, 0.6%, and 0.9%) in the Rd Continuous, Rd18, and MPT Arms,
respectively.
Stroke (CVA) was reported as a serious (2.3%) or severe (2.0%) adverse
drug reaction in the REVLIMID/dexamethasone group compared to
0.9% and 0.9% respectively in the placebo/dexamethasone group.
Discontinuation due to stroke (CVA) was 1.4% in REVLIMID/
dexamethasone group and 0.3% in the placebo/dexamethasone group. In
the NDMM study, CVA was reported as an adverse reaction (all grades:
0.8%, 0.6%, and 0.6%), as a serious adverse reaction (0.8%, 0.6 %, and
0.6%), or as a severe adverse reaction (0.6%, 0.6%, 0.2%) in the Rd
Continuous, Rd18, and MPT arms respectively.
6.2 Postmarketing Experience
The following adverse drug reactions have been identified from the
worldwide post-marketing experience with REVLIMID. Because these
reactions are reported voluntarily from a population of uncertain size, it
is not always possible to reliably estimate their frequency or establish a
causal relationship to drug exposure [see Warnings and Precautions
Section (5.7 to 5.10, and 5.12)]
Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome,
toxic epidermal necrolysis, drug reaction with eosinophilia and systemic
symptoms (DRESS)
Immune system disorders: Angioedema, acute graft-versus-host disease
(following allogeneic hematopoietic transplant), solid organ transplant
rejection
Neoplasms benign, malignant and unspecified (incl cysts and polyps):
Tumor lysis syndrome, tumor flare reaction
Respiratory, thoracic and mediastinal disorders: Pneumonitis
Hepatobiliary disorders: Hepatic failure (including fatality), toxic
hepatitis, cytolytic hepatitis, cholestatic hepatitis, mixed cytolytic/
cholestatic hepatitis, transient abnormal liver laboratory tests
Infections and infestations: Viral reactivation (such as hepatitis B virus
and herpes zoster)
Endocrine disorders: Hypothyroidism, hyperthyroidism
7 DRUG INTERACTIONS
7.1 Digoxin
When digoxin was co-administered with multiple doses of REVLIMID
(10 mg/day) the digoxin C max and AUC 0-∞ were increased by 14%.
Periodic monitoring of digoxin plasma levels, in accordance with clinical
judgment and based on standard clinical practice in patients receiving
this medication, is recommended during administration of REVLIMID.
7.2 Concomitant Therapies That May Increase the Risk of Thrombosis
Erythropoietic agents, or other agents that may increase the risk of
thrombosis, such as estrogen containing therapies, should be used with
caution after making a benefit-risk assessment in patients receiving
REVLIMID [see Warnings and Precautions (5.4)].
7.3 Warfarin
Co-administration of multiple dose REVLIMID (10 mg) with single
dose warfarin (25 mg) had no effect on the pharmacokinetics of total
lenalidomide or R- and S-warfarin. Expected changes in laboratory
assessments of PT and INR were observed after warfarin administration,
but these changes were not affected by concomitant REVLIMID
administration. It is not known whether there is an interaction between
dexamethasone and warfarin. Close monitoring of PT and INR is
recommended in multiple myeloma patients taking concomitant warfarin.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy
outcomes in females exposed to REVLIMID during pregnancy as well as
female partners of male patients who are exposed to REVLIMID. This
registry is also used to understand the root cause for the pregnancy.
Report any suspected fetal exposure to REVLIMID to the FDA via the
MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation
at 1-888-423-5436.
Risk Summary
Based on the mechanism of action and findings from animal studies [see
Data], REVLIMID can cause embryo-fetal harm when administered to a
pregnant female and is contraindicated during pregnancy [see Boxed
Warning, Contraindications (4.1), and Use in Specific Populations (5.1)].
REVLIMID is a thalidomide analogue. Thalidomide is a human teratogen,
inducing a high frequency of severe and life-threatening birth defects
such as amelia (absence of limbs), phocomelia (short limbs),
hypoplasticity of the bones, absence of bones, external ear abnormalities
(including anotia, micropinna, small or absent external auditory canals),
facial palsy, eye abnormalities (anophthalmos, microphthalmos), and
congenital heart defects. Alimentary tract, urinary tract, and genital
malformations have also been documented and mortality at or shortly
after birth has been reported in about 40% of infants.
Lenalidomide caused thalidomide-type limb defects in monkey offspring.
Lenalidomide crossed the placenta after administration to pregnant
rabbits and pregnant rats [see Data]. If this drug is used during
pregnancy, or if the patient becomes pregnant while taking this drug,
the patient should be apprised of the potential risk to a fetus.
If pregnancy does occur during treatment, immediately discontinue
the drug. Under these conditions, refer patient to an obstetrician/
gynecologist experienced in reproductive toxicity for further evaluation
and counseling. Report any suspected fetal exposure to REVLIMID to the
FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene
Corporation at 1-888-423-5436.
The estimated background risk of major birth defects and miscarriage for
the indicated population is unknown. The estimated background risk in
the U.S. general population of major birth defects is 2%-4% and of
miscarriage is 15%-20% of clinically recognized pregnancies.
Data
Animal data
In an embryo-fetal developmental toxicity study in monkeys, teratogenicity,
including thalidomide-like limb defects, occurred in offspring when
pregnant monkeys received oral lenalidomide during organogenesis.
Exposure (AUC) in monkeys at the lowest dose was 0.17 times the human
exposure at the maximum recommended human dose (MRHD) of 25 mg.
Similar studies in pregnant rabbits and rats at 20 times and 200 times the
MRHD respectively, produced embryo lethality in rabbits and no adverse
reproductive effects in rats.
In a pre- and post-natal development study in rats, animals received
lenalidomide from organogenesis through lactation. The study revealed
a few adverse effects on the offspring of female rats treated with
lenalidomide at doses up to 500 mg/kg (approximately 200 times the
human dose of 25 mg based on body surface area). The male offspring
exhibited slightly delayed sexual maturation and the female offspring had
slightly lower body weight gains during gestation when bred to male
offspring. As with thalidomide, the rat model may not adequately address