Relapsed/Refractory Patients:

Pomalidomide (CC-4047)

What is Pomalidomide?

Pomalidomide, also known as CC-4047, is an oral immunomodulatory agent (IMiD™) being developed by Celgene. It is similar to Thalomid^® (thalidomide) and Revlimid^® (lenalidomide) but is more potent.

What do we know about Pomalidomide’s activity in myeloma?

Single-agent Pomalidomide

Notable anti-myeloma activity was seen in a Phase I study of daily pomalidomide in patients with relapsed or refractory myeloma (n=24). Seventeen percent of patients achieved a complete response (CR) and 54% of patients achieved a partial response (PR) or better. Toxicities that required dose adjustments or discontinuation of therapy included deep vein thrombosis (DVT) and neutropenia.

An alternate day schedule of pomalidomide was evaluated in a small Phase II trial in patients with relapsed myeloma (n=20). This dose schedule reduced the side effects, but retained the anti-myeloma activity.

• Ten percent of patients achieved a CR and 50% of patients achieved a PR.

Combination Studies

A subsequent Phase II trial, which included 60 patients with relapsed/refractory myeloma showed the combination of pomalidomide (2mg/day) and low-dose dexamethasone to be highly active.

• Fifteen percent of patients achieved a CR or stringent CR, 27% achieved a very good partial response, and the overall response rate was 65% after a median follow-up of over 27 months.
• The combination was active in patients who were refractory to Velcade or Revlimid, as well as in patients considered to have high-risk myeloma based on cytogenetics.


• The median time until disease progressed was 11.6 months.


• Seventy-six percent of patients were alive at 2 years.


• Low blood cell and platelet counts were the most common severe side effects seen.


• Aspirin was given to prevent DVT, and only one patient developed a blood clot.

Pomalidomide plus low-dose dexamethasone was also shown to be active and well-tolerated in patients whose disease no longer responded to Revlimid.

• An overall response rate of 32% was seen, including very good partial responses in 9% and partial responses in 23% of patients, in a small study evaluating a 2 mg/day dose (n=34).
• Preliminary results of a subsequent Phase II trial evaluating a 4 mg/day dose showed a similar overall response rate of 35% among the 61 patients, with most patients responding within the first or second cycle of therapy.
• In both studies, the main severe side effects were low blood cell and platelet counts. Fatigue was also reported.
  • Other side effects included neuropathy, high blood sugar, and pneumonia. Blood clots were seen in a few patients receiving the higher 4 mg/day dosing.

Pomalidomide, alone and in combination with dexamethasone, was evalauted in a Phase I/II study in patients with relapsed and refractory myeloma who had previously been treated with both Revlimid and Velcade® (bortezomib). This trial was facilitated by the Multiple Myeloma Research Consortium (MMRC).

• The Phase I portion of the study identified the maximum tolerated dose of pomalidomide (4 mg once daily on days 1-21 of a 28-day cycle).


• Pomalidomide had a favorable safety profile, with low neutrophil counts as the primary dose-limiting toxicity.


• In the second phase of the study, clinical benefit (at least a partial response or better) was seen in 25% of the 120 evaluable patients according to International Myeloma Working Group (IMWG) Criteria.


• Toxicities were manageable, with low blood cell and platelet counts and infections the most common side effects seen.


• This dosing schedule was selected to be used in Phase III testing.


• This portion of the study is ongoing.

Two additional Phase II studies evaluated various pomalidomide plus low-dose dexamethasone doses/regimens in myeloma that no longer responded to both Velcade and Revlimid. The combination demonstrated activity in these heavily-pretreated patients.

Taken together, the data from all these Phase II studies provide evidence that there is no cross-resistance between pomalidomide and Revlimid. Pomalidomide is the only agent that has been shown to produce responses in myeloma that is no longer responds to Velcade and Revlimid.

How is Pomalidomide currently being studied in myeloma?

Pomalidomide is being evaluated in a Phase III trial that is comparing the efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in patients with refractory or relapsed and refractory myeloma.

• This international study, which is also known as the NIMBUS study, is expected to enroll 426 patients.


• Pomalidomide is being given at 4 mg once daily on days 1-21 of a 28-day cycle.


• It will evaluate the time it takes for the disease to progress while on treatment, as well as the number of patients responding to treatment, safety, quality of life, and other measures.

An international Phase III study is also evaluating the safety and efficacy of pomalidomide in patients with refractory or relapsed and refractory myeloma who were enrolled in an earlier pomalidomide study and discontinued treatment with high-dose dexamethasone due to disease progression.

Pomalidomide monotherapy is being evaluated in several Phase II studies.

• One study is comparing the efficacy and biological effects of continuous versus intermittent dosing of pomalidomide in patients with relapsed/refractory myeloma.


• One study is set to begin enrolling patients who have been determined to have high-risk relapsing/refractory myeloma based on gene expression profiling (GEP).

Pomalidomide is also being evaluated in combination with other therapies, including:

• In a Phase II study in combination with Biaxin® (clarithromycin) and dexamethasone (ClaPd) in patients with relapsed or refractory disease who have failed prior treatment with Revlimid +/- corticosteroids.


• In combination with Velcade and dexamethasone in a Phase I/II study patients with relapsed or refractory myeloma, which is set to begin.




To find a clinical trial, call 1-866-603-MMCT (-6628) or click here to go to the MMRF Patient Navigator Program.