Latest & Greatest
benefits – especially compared with
other treatments for chronic pain,” said
Thomas R. Frieden, MD, MPH, director
of the CDC. He further noted that the
guidelines are meant as “a tool for doctors and patients to chart a safer course.”
The CDC made its recommendations based on a literature review of
observational studies, as well as consultation with experts and comments from
partner organizations and the public.
Results from the review were published
in the Journal of the American Medical Association. Overall, the researchers
determined that opioids were associated
with increased risks, including opioid
use disorder, overdose, and death, with
dose-dependent effects. They noted,
however, that that the studies in the
literature review had notable limitations
and none evaluated the long-term benefit
of opioids for chronic pain.
The guidelines include 12 recommendations, following the key principles
of using the lowest-possible effective
dosage of opioids and a preference for
non-opioid therapies as first-line chronic
pain management. Key recommendations include:
• Health-care providers should
prescribe over-the-counter pain
relievers (ibuprofen or aspirin) prior
to prescribing more highly addictive
opioids.
• Health-care providers should reduce
patient supply of opioids (3-7 days
for short-term pain).
• Non-pharmacologic therapy and
non-opioid pharmacologic therapy
are preferred for chronic pain.
• Before starting opioid therapy for
chronic pain, clinicians should establish treatment goals with all patients
regarding benefits and risks of opioid
treatment.
• Clinicians should prescribe immediate-release opioids instead of
extended-release/long-acting opioids.
• Clinicians should review the patient’s
history of controlled substance
prescriptions using state prescription drug monitoring program data
to determine whether the patient is
receiving opioid dosages or dangerous combinations that put him or her
at high risk for overdose.
• Clinicians should avoid prescribing
opioid pain medication and benzodiazepines concurrently whenever
possible.
The guidelines also offer specific information on medication selection, dosage,
duration, and when and how to reassess
24
ASH Clinical News
progress and discontinue medication if
needed.
The use of opioids for chronic pain has
been a topic of debate recently, with some
arguing that increased prescribing and
sales of opioids have created an epidemic
of overuse and abuse, while physicians
and others in the pharmaceutical industry
fear that restrictions on opioids will create
unfair hurdles for patients who need the
medication.
While these guidelines do not apply to
prescriptions for patients receiving cancer
or palliative or end-of-life treatment or
those who have had recent surgery, some
are concerned that they would impact
cancer survivors who have continuing
pain. The American Medical Association,
for one, has expressed concern that the
science backing these recommendations is
questionable and that the guidelines could
conflict with some state laws.
Sources: CDC press release, March 15, 2016; Dowell D, Haegerich TM,
Chou R. CDC guideline for prescribing opioids for chronic pain—United
States, 2016. JAMA. 2016 March 15. [Epub ahead of print.]
FDA Approves New
Formulation of
Melphalan
The U.S. FDA approved a new formulation of melphalan injection for use as a
high-dose conditioning treatment prior
to hematopoietic cell transplantation in
multiple myeloma (MM) patients and for
the palliative treatment of MM patients
for whom oral therapy is not appropriate.
This is the first product to be approved
for the high-dose conditioning indication
in MM. The new formulation of melphalan does not contain propylene glycol
and can be stabilized at room temperature for four hours in addition to the one
hour following reconstitution.
Approval was granted based on
results from a multi-center, open-label,
phase IIb trial in which 61 patients
received 200 mg/m2 of this melphalan
formulation followed by transplant. The
overall response r ate was 95 percent,
and the complete response rate was 31
percent. All patients had successful myeloablation and subsequent neutrophil
and platelet engraftment with no mortality reported at day 100.
The drug has a Boxed Warning for
severe bone marrow suppression, hypersensitivity, and leukemogenicity. The
most common adverse events (observed
in ≥50% of patients) were neutropenia,
leukopenia, lymphopenia, and thrombocytopenia. Diarrhea, nausea, fatigue,
hypokalemia, anemia, and vomiting were
the most common non-hematologic
adverse events.
Source: Spectrum Pharmaceuticals press release, March 15, 2016.
FDA Approves New
Genetic Therapy for
Hemophilia A
The U.S. FDA approved Kovaltry™
antihemophilic factor (recombinant),
an unmodified, full-length factor VIII
compound, for the treatment of hemophilia A in children and adults. The drug
is infused prophylactically two to three
times per week for adolescents and adults
and two to three times per week or every
other day for pediatric patients to reduce
the risk of bleeding.
The approval was based on results
from three Long-Term Efficacy OpenLabel Program in Severe Hemophilia
A Disease (LEOPOLD) clinical trials,
which were carried out in more than 200
children and adults with severe hemophilia A from 60 sites in 25 countries
worldwide. The drug demonstrated
control of and protection from bleeds
when used prophylactically two to three
times per week in each multi-center,
open-label, uncontrolled study. These
trials established the pharmacokinetics,
safety, and efficacy of the recombinant
antihemophilic factor in previously
treated children, adolescents, and adults.
The most frequently reported adverse
events in these trials (reported in ≥3%
of patients) were headache, pyrexia, and
pruritus.
athy, and the recommendation calls for
the use of mechanical means to lower
serum light chain concentration, such as
plasmapheresis or high-cut-off dialysis
filters, though these techniques remain
controversial due to a lack of clinical
trial evidence.
Clinical management should follow
the IMWG criteria for renal reversibility, including high fluid intake and
the use of a bortezomib-based myeloma
therapy, with a preferred combination
of bortezomib/cyclophosphamide/
dexamethasone in this patient population. The IMWG document states that
thalidomide is effective in patients with
renal impairment and requires no dose
modifications, and lenalidomide is effective and safe mostly in patients with
mild to moderate renal impairment.
Patients with severe renal impairment
or those on dialysis who are taking
lenalidomide need to be monitored
closely for hematologic toxicity. Carfilzomib can be used in patients with CrCl
>15 mL/min, and ixazomib can be used
in combination with lenalidomide and
dexamethasone in those with CrCl >30
mL/min. The recommendation did not
comment on recently approved monoclonal antibodies (daratumumab and
elotuzumab).
Source: Dimopoulos MA, Sonneveld P, Leung N, et al. International
Myeloma Working Group recommendations for the diagnosis and
management of myeloma-related renal impairment. J Clin Oncol. 2016
March 14. [Epub ahead of print]
Sources: Bayer press release, March 17, 2016.
IMWG Updates
Myeloma-Related
Renal Impairment
Management Recommendations
The International Myeloma Working
Group (IMWG) has updated its recommendations for the diagnosis and
management of myeloma-related renal
impairment. According to the new
document, a renal assessment should
be performed at diagnosis and at every
follow-up due to the worse prognosis of
multiple myeloma when renal impairment is involved.
The authors of the guidelines, which
were published in the Journal of Clinical
Oncology, also acknowledge that this effect on prognosis persists even when the
renal impairment is reversed. IMWG
defines renal impairment in symptomatic myeloma as elevated serum creatinine
(>2 mg/dL) or reduced creatinine clearance (CrCl; <40 mL/min).
The most common cause for renal
impairment is light chain cast nephrop-
FDA Grants Orphan
Designation to Iomab-B
for Older Patients
With AML
The U.S. FDA granted orphan drug designation to Iomab-B for the treatment of relapsed/refractory acute myeloid leukemia
(AML) prior to hematopoietic cell transplantation in older patients. Iomab-B is a
radioimmunoconjugate composed of BC8
(a novel urine monoclonal antibody) and
iodine-131 radioisotope. A multi-center,
phase III trial will begin soon to evaluate
Iomab-B in patients age ≥55 years with
relapsed/refractory AML. ●
Source: U.S. FDA press release, March 30, 2016.
May 2016