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Pom/Dex Has Activity in Lenalidomide-, Bortezomib-Refractory Patients
January 14, 2009
Thalidomide Analogue Pomalidomide in Phase II with Dexamethasone

A combination of the investigational thalidomide analogue pomalidomide and low-dose
dexamethasone has produced good response rates in patients with relapsed/refractory multiple
myeloma, reported investigators at the 50th Annual Meeting of the American Society of Hematology
in San Francisco.
In a phase II study, the combination produced a 58% overall response rate and a 25% combined
complete response/very good partial response (VGPR) rate, reported Martha Q. Lacy, MD, associate
professor of medicine at the Mayo Clinic in Rochester, Minnesota.
The reduced dexamethasone dose appears to contribute to the regimen’s overall safety profile, with a
relatively low incidence of thrombosis, Dr. Lacy said. She noted that in the registration trials for a
lenalidomide/dexamethasone combination, the remission rate was about 60%.
“Our current study is showing remission rates that are very similar using one-third of the dose of
dexamethasone. We think this may account for the low DVT rate we’re seeing in this population,” she
“We’ve just seen very impressive results with this novel immunomodulatory drug,” commented
Kenneth Anderson, MD, professor of medicine at Harvard Medical School and medical director of the
Kraft Family Blood Center at the Dana-Farber Cancer Institute in Boston.
Evangelos Terpos, MD, director of the Department of Medical Research at General Airforce Hospital,
Athens, Greece, commented that the efficacy of this and other agents in this challenging patient
population is highly encouraging.
Pomalidomide (CC4047) is a thalidomide analogue that is structurally similar to both the parent
compound and to lenalidomide.
“These drugs have very similar structure but they have important differences in both potency and the
side effect profile,” Dr. Lacy said.
In in vitro studies, pomalidomide had antiangiogenic potency similar to that of thalidomide,
significantly better anti-inflammatory activity against monocytes, and superior ability to inhibit T-cells
and natural killer (NK) cells. Unlike thalidomide, the novel agent has the ability to inhibit regulatory T-
cells, and displays antibody-dependent cellular cytotoxicity. Pomalidomide has also shown single-
agent activity in phase I studies.
Dr. Lacy reported results of the first phase 2 trial of pomalidomide in combination with low-dose dexamethasone in patients with relapsed or refractory multiple myeloma. The goals of the study were to assess the response rate and duration of remission with the combination, and to evaluate toxicity, overall survival, and progression-free survival rates. The authors defined a confirmed response as a CR, PR, or VGPR as determined by the International Myeloma Working Group Uniform Response criteria. The starting doses were pomalidomide 2 mg by mouth daily for days 1-28 continuously, dexamethasone 40 mg by mouth daily on days 1, 8, 15 and 22, with aspirin 325 mg daily for days 1-28 for thrombosis prophylaxis. The trial was initially open to 37 patients, and was expanded when high activity of the combination was seen. A total of 60 patients (36 men and 24 women) with measurable disease who had relapsed or refractory disease after undergoing 2 or 3 prior regimens have been enrolled, The median patient age was 65.5 years, range 35-88, and one-third had International Staging System (ISS) stage III disease. Neuropathy at baseline was seen in 45% of patients, with 5% having grade II neuropathy. Two-thirds of the patients had more than one prior treatment regimen, two-thirds had previously undergone stem cell transplant, and 60% had previously received an IMiD. With a median follow-up of 4 months, the overall response rate was 58% with a 25% combined complete or very good partial response rate. One-third of the patients (33%) had a partial response, stable disease was seen in 18%, disease progression occurred in 22%, and one patient died. Hematologic toxicities with the combination consisted primarily of neutropenia, with grade 3-4 neutropenia occurring in 32%, but other forms of myelosuppression were uncommon. Grade 3-4 non-hematologic toxicities, occurred in 28% of patients, with events consisting primarily of fatigue. There was one death due to pneumonia while the patient was neutropenic, and this event was attributed to treatment. There were no grade 3 or 4 neuropathies, and no thromboembolic disease. Of the 256 cycles administered, pomalidomide dose reduction was required in 13% of patients, and dexamethasone dose reduction was required in 32%. “We feel there may be a niche for this drug in the treatment of patients who have relapsed after other novel agents, and we are specifically pursuing phase II trials to figure the response rates in these lenalidomide-refractory and bortezomib-refractory patients,” Dr. Lacy said. Reference Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) Plus Low-Dose Dexamethasone (Pom/dex) Is Highly Effective Therapy in Relapsed Multiple Myeloma. Blood (ASH Annual Meeting Abstracts). 2008;112(11):Abstract 866.



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