Researchers from the Arkansas Cancer Research Center, Mayo
Clinic, and M.D. Anderson Cancer Center presented data at the 42nd annual
meeting of the American Society of Hematology on clinical trials evaluating
the safety and efficacy of Thalomid (thalidomide) as a single agent and in
combination treatment for multiple myeloma. Studies presented included new
clinical trial data on the use of Thalomid alone and Thalomid in combination
with conventional therapies for treatment of patients with early stage
multiple myeloma. In addition, clinical data presented was consistent with
previously published results on the potential use of Thalomid in treating
refractory multiple myeloma and included survival data of patients.
"The new data presented at this meeting greatly expands our knowledge base
on Thalomid's potential role in treating multiple myeloma both as a single
agent and in combination with a range of chemotherapeutic agents. For the
first time, results of clinical trials studying newly diagnosed myeloma
patients with Thalomid in combination with other agents were discussed," said
Sol J. Barer, Ph.D., President and COO of Celgene Corporation. "We will
continue to expand our clinical trial programs for Thalomid, intended to lead
to a supplemental New Drug Application to the FDA in 2001."
Newly Diagnosed Multiple Myeloma Trials
Researchers from the Mayo Clinic led by S. V. Rajkumar, M.D., presented an
interim analysis of an ongoing trial using thalidomide alone or in combination
with dexamethasone for treatment of newly diagnosed patients with multiple
myeloma. Forty-two (26 with active disease, 16 with smoldering/indolent
disease) patients were randomized to receive a starting thalidomide dose of
200 mg/day escalated by 200 mg every two weeks according to tolerance to a
maximum 800 mg/day alone or with 40mg/day of oral dexamethasone.
Seventy-seven percent of patients with active disease achieved response
(greater than or equal to 50 percent reduction in serum and/or urine
monoclonal protein (M-protein)). Eighty-six percent of patients who received
thalidomide dose escalation and 74 percent of patients with the constant
thalidomide dose in combination with dexamethasone achieved response. For
patients receiving thalidomide alone, 38 percent experienced a response. Due
to grade 3-4 skin toxicity in two patients among the first seven patients in
the thalidomide plus dexamethasone treatment arm, the dose escalation of
thalidomide was stopped and all patients continued receiving 200 mg/day of
thalidomide alone or in combination with dexamethasone. Major side effects
observed include rash in three patients, sedation, constipation and myalgias
in one patient each.
"Based on these encouraging interim results, thalidomide, in combination
with dexamethasone, may be an active first-line treatment for patients newly
diagnosed with active multiple myeloma," says Dr. Rajkumar. "Although further
study and analysis is needed to confirm these preliminary results, these data
suggest that there may be a potential use for this combination in treating
patients with myeloma."
Refractory Multiple Myeloma Trials
Bart Barlogie, M.D., Ph.D., Director of the Arkansas Cancer Research
Center, presented results on long-term follow-up of 169 patients enrolled in a
dose escalation trial evaluating the potential use of thalidomide (starting
dose 200 mg/day escalated by 200 mg every two weeks according to tolerance to
a maximum 800 mg/day) as a single agent for refractory multiple myeloma.
According to the data presented, 36 percent of patients achieved at least
25 percent reduction in M-protein. Reductions in paraproteins were
associated with corresponding reduction in bone marrow plasmacytosis, recovery
from anemia/thrombocytopenia and uninvolved immunoglobulins.
Twenty-four patients remain on study; the main reasons for discontinuing
therapy include disease progression in 98 patients (22 deaths) and toxicity in
28 patients (4 deaths). With a median follow-up of 22 months among 84 alive
patients, 48 +/- 6 percent are projected alive at 2 years and 20 +/- 6 percent
are projected event-free. For perspective, Dr. Barlogie also outlined an 8
month landmark analysis (when more than 90 percent of patients had achieved
more than 25 percent M-protein reduction) was conducted among 124 surviving
patients. At 18 months, 78 percent of 56 responding patients (25 percent
reduction) survived compared to 53 percent among the remaining 68
non-responders (p= 0. 02). For this high-risk patient group at 18 months,
there is a 55 percent overall patient survival rate with 30 percent event free
survival, and durable response in 26 percent. Major side effects seen were
sedation, confusion, depression, tremor, constipation, weakness and sensory
neuropathy, somnolence and tingling/numbness in ten percent of patients who
received a 400 mg dose of thalidomide.
"Our results suggest that thalidomide may have single agent activity in
advanced and refractory high risk multiple myeloma," says Dr. Barlogie.
"These results are consistent with our earlier observations that thalidomide
may improve patient survival in this very difficult disease."
The data presented suggest that direct anti-tumor activity of thalidomide
on human multiple myeloma cells may result in positive responses when used
alone or in combination therapy for patients with advanced disease. In
addition, the data suggest that thalidomide may act synergistically with other
Twenty-one additional abstracts studying thalidomide in the setting of
multiple myeloma were presented, including results on thalidomide in
combination with conventional therapies for relapsed or refractory multiple
myeloma. There were additional abstracts presented at this meeting studying
the potential use of thalidomide in myelodysplastic syndromes, Castleman's
disease and acute myeloid myeloma.
About Multiple Myeloma
There are approximately 40,000 people in the United States living with
multiple myeloma and 13,000 new cases of multiple myeloma are diagnosed each
year in the United States, making it the second most common blood cancer.
Incurable with conventional chemotherapy, multiple myeloma is a malignant
cancer of the plasma cells, which are a type of white blood cell found in many
tissues of the body, but mainly in the bone marrow. As the cancer grows it
destroys normal bone tissue, causing pain and crowding out normal blood cell
production. There are nearly 11,000 deaths expected during 2000, according to
the Multiple Myeloma Research Foundation.
Thalidomide is contraindicated in pregnant women and women capable of
becoming pregnant. Even a single capsule taken by a pregnant woman can cause
severe birth defects or death to an unborn baby. To minimize this risk, only
prescribers and pharmacies registered with the System for Thalidomide
Education and Prescribing Safety (S.T.E.P.STM) distribution program may
prescribe or dispense Thalomid(R) (thalidomide). Other adverse drug reactions
known to be associated with thalidomide therapy include: peripheral
neuropathy, a common, potentially severe side effect that may be irreversible;
drowsiness/somnolence; dizziness/orthostatic hypotension; neutropenia;
hypersensitivity reactions; and increased HIV-viral load. Physicians should
consult full prescribing information about these and other adverse reactions
prior to initiating treatment with Thalomid(R).
Thalomid(R) (thalidomide), manufactured by Celgene Corporation, received
U.S. Food and Drug Administration (FDA) clearance on July 16, 1998 for the
acute treatment of cutaneous manifestations of moderate to severe erythema
nodosum leprosum (ENL) and as maintenance therapy for prevention and
suppression of cutaneous manifestation recurrences. Thalomid(R) is not
indicated as monotherapy for ENL treatment in the presence of moderate to
Celgene Corporation, headquartered in Warren, New Jersey, is an
independent biopharmaceutical company engaged in the discovery, development
and commercialization of small molecule drugs for cancer and immunological
diseases. Please feel free to visit the Company's website at