Medical Innovation Gives Patients with Myeloma Another Chance at Life

(BPT) – When Paula Van Riper felt a slight but annoying ache in her thigh 13 years ago, she was prompted to visit her doctor. No one expected to find a large mass of abnormal plasma cells in her femur, caused by multiple myeloma – a rare form of blood cancer that can lead to the formation of tumors in the bone marrow. Affecting more than 71,000 Americans, multiple myeloma ranks as the second most prevalent blood cancer after non-Hodgkin’s lymphoma.1 According to the American Cancer Society, 21,700 additional cases were diagnosed in the U.S. last year.2

Van Riper immediately underwent hip replacement surgery. When she was diagnosed with multiple myeloma, she researched the disease and found it was associated with a two to three year survival rate.

“I was a perfectly healthy woman and lived a very active life,” said Van Riper. “It was obviously a devastating diagnosis.”

Multiple myeloma causes excessive production of white blood cells. In many cases, the tumors that can result lead to bone destruction and fractures, which is what caused the initial pain in Van Riper’s leg. The cause of multiple myeloma is unknown, but it is believed that environmental factors, including exposure to chemicals such as pesticides, benzene and paint sprays, may play a significant role. The disease primarily affects older males and disproportionately impacts African Americans.3

There is not yet a cure for multiple myeloma, but significant advances in medical innovation and research over the past 10 years have helped make this type of cancer a manageable condition for many. Since her surgery 13 years ago, Van Riper has tried several different therapies to manage her cancer, as is the typical course for myeloma patients. Nearly 10 to 30 percent of newly diagnosed patients are refractory to treatment, meaning they do not respond to the therapy, and nearly all myeloma patients who achieve an initial response will eventually relapse, requiring them to explore other regimens.

For these patients, a new option is now available. The U.S. Food and Drug Administration (FDA) recently approved POMALYST® oral therapy (pomalidomide), a new pill for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib therapy and have demonstrated disease progression on or within 60 days of completion of the last therapy.

“POMALYST has shown to be an effective and well tolerated alternative for heavily pre-treated patients or for those who have exhausted multiple therapies, including standard of care,” said Dr. Paul Richardson, from the Dana-Farber Cancer Institute in Boston, who was the primary investigator for the POMALYST clinical trial that was the basis for the FDA approval. “We are excited to have yet another treatment to offer patients with multiple myeloma, to potentially help extend remissions in this incurable disease.”

More than a decade after her diagnosis, Van Riper continues to live an active life, and her disease is currently under control. She participated in the clinical trial for POMALYST, which she continues to take today. Because this new drug is a pill, Van Riper does not need to go to the hospital and is thus able to receive treatment with minimal disruption to her daily life; helped by this convenience, she is able to maintain her full-time job as assistant dean at Rutgers University.

“It’s not just about living longer,” said Van Riper. “It’s about living well.”

These recent medical innovations have allowed Van Riper to adhere to this credo, and she maintains a positive attitude despite her cancer.

“I sometimes say my cancer diagnosis was the best and the worst thing that ever happened to me,” she said. “It allowed me to open my world to the understanding that my life is very precious. Prior to diagnosis, I know I did not fully appreciate life’s many blessings.”

POMALYST® is a registered trademark of Celgene Corporation

About POMALYST®

POMALYST® oral therapy comprises pomalidomide, an IMiDs® compound. POMALYST and other IMiDs compounds continue to be evaluated in over 100 clinical trials.

POMALYST® (pomalidomide) is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS THROMBOEMBOLISM

Embryo-Fetal Toxicity

POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment

POMALYST is only available through a restricted distribution program called POMALYST REMSTM.

Venous Thromboembolism

Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Prophylactic anti-thrombotic measures were employed in the clinical trial. Consider prophylactic measures after assessing an individual patient’s underlying risk factors

CONTRAINDICATIONS: Pregnancy

POMALYST can cause fetal harm and is contraindicated in females who are pregnant. 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 hazard to a fetus
Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

Females of Reproductive Potential: Must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of POMALYST therapy. Must obtain 2 negative pregnancy tests prior to initiating therapy.
Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm
Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST

POMALYST REMS Program

Because of the embryo-fetal risk,POMALYST is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called “POMALYST REMS.” Prescribers and pharmacists must be certified with the program; patients must sign an agreement form andcomplywith the requirements. Further information about the POMALYST REMS program is available at [celgeneriskmanagement.com] or by telephone at 1-888-423-5436.

Venous Thromboembolism: Patients receiving POMALYST have developed venous thromboembolic events reported as serious adverse reactions. In the trial, all patients were required to receive prophylaxis or antithrombotic treatment. The rate of DVT or PE was 3%. Consider anticoagulation prophylaxis after an assessment of each patient’s underlying risk factors.

Hematologic Toxicity: Neutropenia of any grade was reported in 50% of patients and was the most frequently reported Grade 3/4 adverse event, followed by anemia and thrombocytopenia. Monitor patients for hematologic toxicities, especially neutropenia, with complete blood counts weekly for the first 8 weeks and monthly thereafter. Treatment is continued or modified for Grade 3 or 4 hematologic toxicities based upon clinical and laboratory findings. Dosing interruptions and/or modifications are recommended to manage neutropenia and thrombocytopenia.

Hypersensitivity Reactions: Patients with a prior history of serious hypersensitivity associated with thalidomide or lenalidomide were excluded from studies and may be at higher risk of hypersensitivity.

Dizziness and Confusional State: 18% of patients experienced dizziness and 12% of patients experienced a confusional state; 1% of patients experienced grade 3/4 dizziness, and 3% of patients experienced grade 3/4 confusional state. Instruct patients to avoid situations where dizziness or confusion may be a problem and not to take other medications that may cause dizziness or confusion without adequate medical advice.

Neuropathy: 18% of patients experienced neuropathy (approximately 9% peripheral neuropathy). There were no cases of grade 3 or higher neuropathy adverse reactions reported.

Risk of Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.

ADVERSE REACTIONS

In the clinical trial of 219 patients who received POMALYST alone (n=107) or POMALYST + low-dose dexamethasone (low-dose dex) (n=112), all patients had at least one treatment-emergent adverse reaction.

In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common adverse reactions (≥30%) included fatigue and asthenia (55%, 63%), neutropenia (52%, 47%), anemia (38%, 39%), constipation (36%, 35%), nausea (36%,22%), diarrhea (34%, 33%), dyspnea (34%, 45%), upper respiratory tract infection (32%, 25%), back pain (32%, 30%), and pyrexia (19%, 30%)
90% of patients treated with POMALYST alone and 88% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent NCI CTC Grade 3 or 4 adverse reaction
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common Grade 3/4 adverse reactions (≥15%) included neutropenia (47%, 38%), anemia (22%, 21%), thrombocytopenia (22%, 19%), and pneumonia (16%, 23%). For other Grade 3 or 4 toxicities besides neutropenia and thrombocytopenia, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion
67% of patients treated with POMALYST and 62% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent serious adverse reaction
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common serious adverse reactions (≥5%) were pneumonia (14%, 19%), renal failure (8%, 6%), dyspnea (5%, 6%), sepsis (6%, 3%), pyrexia (3%, 5%) dehydration (5%, 3%), hypercalcemia (5%, 2%),urinary tract infection (0%, 5%), and febrile neutropenia (5%, 1%)

DRUG INTERACTIONS

No formal drug interaction studies have been conducted with POMALYST. Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is also a substrate for P-glycoprotein (P-gp). Coadministration of POMALYST with drugs that are strong inhibitors or inducers of CYP1A2, CYP3A, or P-gp should be avoided. Cigarette smoking may reduce pomalidomide exposure due to CYP1A2 induction. Patients should be advised that smoking may reduce the efficacy of pomalidomide.

USE IN SPECIFIC POPULATIONS

Pregnancy: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436.

Nursing Mothers: It is not known if pomalidomide is excreted in human milk. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from POMALYST, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness of POMALYST in patients under the age of 18 have not been established.

Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients greater than or equal to 65 years of age were more likely than patients less than or equal to 65 years of age to experience pneumonia.

Renal and Hepatic Impairment: Pomalidomide is metabolized in the liver. Pomalidomide and its metabolites are primarily excreted by the kidneys. The influence of renal and hepatic impairment on the safety, efficacy, and pharmacokinetics of pomalidomide has not been evaluated. Avoid POMALYST in patients with a serum creatinine >3.0 mg/dL. Avoid POMALYST in patients with serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN.

Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.

1 Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Prevalence

2 American Cancer Society, Cancer Facts & Figures 2012, Estimated New Cancer Cases and Deaths by Sex, US, 2012

3 National Cancer Institute, “A Snapshot of Myeloma”: http://www.cancer.gov/researchandfunding/snapshots/pdf/Myeloma-Snapshot.pdf, accessed 1.28.13