Drugs Used in the
Treatment of Multiple
Myeloma
Myeloma Canada National
Conference
2011-September-24
Toronto, Ontario
Carlo De Angelis, RPh, PharmD
Clinical Pharmacy Coordinator - Oncology
Objectives
At the end of this educational
program,
you will be able to:
• Recall common side effects
associated with Multiple Myeloma
treatment
• Apply the information discussed to
help prevent or reduce the severity
of side effects of Multiple Myeloma
treatment
Improved Survival in Multiple
Myeloma Kumar SK et al. Blood 2008
Advances in Multiple Myeloma
Kyle RA and Rajkumar SV Blood 2008
Thalidomide - Adverse Effects
Mateos MV Cancer Treat Rev 2010
• Single agent
• Somnolence, asthenia, rash, peripheral edema,
dizziness, constipation, dyspnea, leukopenia
• Peripheral neuropathy
• Cummulative and dose dependent
• Parasthesia, hyperaesthesia, numbness,
coldness, pallor
• Symmetrical hands and feet
• Caution in patient with predisposition
• Early detection critical
• Discontinue at first sign of symptoms
Thalidomide - Adverse Effects
• Combination with dexamethasone
• Grade 3 (alone versus combination)
•
•
•
•
•
•
Constipation - 68% versus 55%
Fatigue - 39% versus 55%
Thrombosis - 4% versus 15%
Infection - 14% versus 13%
Neuropathy - 3% versus 5%
Rash - 0% versus 4%
• Overall Grade 4 - 15% versus 31%
Thalidomide - Dose Adjustment for
Peripheral Neuropathy
Mateos MV Cancer Treat Rev 2010
Grade 1
• Maintain dose and monitor
Grade 2
• Reduce dose of thalidomide 50%
Grade 3 or 4
• Discontinue therapy
• Resume at 50% previous dose
Therapeutic Interventions for
Peripheral Neuropathy
• Opioids
• Morphine, hydromorphone,
oxycodone
• Gabapentin
• Pregabalin
• Duloxetine
• Tricyclic antidepressants
Thrombosis
Mateos MV Cancer Treat Rev 2010
• Single agent - 2% to 4%
• In combination - 10% to 35%
• Ususllay occurs within the first 3 - 12 months of
therapy
• Risk factors
• Previous history of VTE, obesity, presence of central
venous catheter, high tumor burden, high dose
dexamethsone
• Prevention
•
≥ 2 risk factors - anticoagulation
• LMWH or warfarin
•  1 risk factor - low dose aspirin
Lenalidomide - Adverse Effects
Morgan GJ et al. Lancet Oncol 2006
Lenalidomide and Myelosupression
• Lenalidomide is primarily eliminated through the
kidneys
• Thrombocytopenia increased when creatinine
clearance was < 50 mL/min 14% versus 5%
• Starting Dosing
• Moderate renal impariment
• CrCl ≥ 30 to < 60 mL/min
• 10 mg daily
• CrCl < 30 mL/min not on dialysis
• 15 mg every 48 hours
• CrCl < 30 mL/min on dialysis
• 5 mg daily
Lenalidomide and Myelosupression
Bortezomib - Adverse Effects
San Miguel J et al. Oncologist 2006
Bortezomib - Thrombocytopenia
• Transient; Not cumulative
• Greater risk if significant bone marrow
involvement with MM
• If platelet count < 30,000/L on day 11 of
cycle
• Repeat count on day 14/15
• Transfuse if necessary
• Reduce dose 25% next cycle
• Caution in patients with platelet count <
50,000/L at start of Tx
Bortezomib - Peripheral Neuropathy
Richardson PG et al. Journal of Clinical Oncology 2006
• Symptoms are primarily sensory
• Feet affected more than hands
• Symptoms include:
• Pain
• Paresthesias or dyesthesias
• Abmornal touch sensations such as
wetness, itchiness, creeping, crawling,
numbness, tingling
• Burning
• Numbness
Bortezomib - Peripheral Neuropathy
Richardson PG et al. Journal of Clinical Oncology 2006
• SUMMIT and CREST trial data
• 35% patients all grades
• Grade 3 - 13%, Grade 4 - < 1%
•
•
•
•
•
•
Symptom improvement or reversible 70% patients
Median time to improvement = 47 days (range 1-529)
Dose reductions in 12% patients
Discontinuation 5% patients
Preexisting peripheral neuropathy - 80%
Patients with no pre-existing peripheral neuropathy 3% developed Grade 3
• In extension study 73% patients reported no
worsening
Bortezomib - Peripheral Neuropathy
Richardson PG et al. Journal of Clinical Oncology 2006
• Dose reduction
• Grade 1 without pain or loss of function
• No action required
• Grade 1 + pain or Grade 2 - reduce dose
• 1.0 mg/m2
• Grade 2 + pain or Grade 3 - hold until
resolved; resume at  dose 0.7 mg/m2 –
once weekly
• Grade 4 - Discontinue Tx
Bortezomib Adverse Effects Take
Home Messages
• While common, side effects can be
managed and are reversible
• Bruising or bleeding may be a sign
of low platelets
• Contact your care team at the cancer
centre
• Peripheral neuropathy
• Make sure you inform your care team
of any symptoms
Shift in Treatment Paradigm
Current
• Use medications at maximum
tolerated doses
Future?
• Use optimal effective dose
•
•
•
•
Reduced intensity
Improved side effect profile
Prolong duration of therapy
Improved Efficacy
Summary
• The availability of new active agents has
revolutionized the treatment of Multiple
Myeloma
• Standard first line therapy include use of
drug combinations of immune modulating
drugs (thalidomide, lenalidomide) and/or
bortezomib
• Side effects prevention/ management
and adherence to treatment are
important factor contributing to success
of treatment
Multiple Myeloma Word Cloud
Rajkumar SV et al. Blood 2010