Pomalidomide was one of the potential new myeloma treatments in the spotlight at the 2011 meeting of the American Society of Hematology (ASH) held earlier this month.

The consensus is that the drug, a chemical relative of thalidomide and Revlimid, performed well during its time on the stage.

Research findings about pomalidomide (Pomalyst) were summarized in four of the meeting’s oral presentations and a number of poster presentations.

Most of these presentations examined pomalidomide’s efficacy and safety as a potential treatment for relapsed and refractory myeloma patients.

Physicians and industry analysts continue to be impressed with the drug’s performance in this important patient population.  The response to pomalidomide among patients previously treated with both Revlimid and Velcade drew particular attention.

Important information about pomalidomide also was presented during a financial analyst briefing hosted by Celgene Corporation (NASDAQ: CELG) during the ASH meeting.

Celgene is the company developing pomalidomide as a potential myeloma treatment.

During the analyst briefing, Celgene provided updates relevant to when pomalidomide might become generally available for use in the United States and in Europe.

Based on these updates and the findings summarized in various ASH presentations, financial analysts now expect pomalidomide to be approved by the U.S. Food and Drug Administration sometime between mid-2012 and mid-2013.

In addition, analysts expect that approval in Europe could occur as early as mid 2013.

Details of the key ASH oral presentations about pomalidomide – as well as one key poster presentation – are summarized below.

Comparison Of Pomalidomide Alone Or In Combination with Low-Dose Dexamethasone In Relapsed And Refractory Myeloma Patients

The goal of this Phase 1/2 clinical trial was to determine the efficacy and safety of pomalidomide alone versus pomalidomide plus low-dose dexamethasone (Decadron) in patients with myeloma that is refractory to Revlimid (lenalidomide) and Velcade (bortezomib).

Dr. Paul Richardson of the Dana-Farber Cancer Institute in Boston presented results of the Phase 2 study.  (Dr. Richardson has made available a copy of his presentation (pdf) as a courtesy to the Beacon's readers.)

According to Dr. Richardson, the trial results indicate that both regimens are active and generally well tolerated in patients with advanced multiple myeloma, including patients refractory to Revlimid and Velcade. He also noted that pomalidomide plus dexamethasone appears to be more active without increases in side effects compared to pomalidomide alone.

A total of 221 patients were enrolled in the trial, with a median of five prior therapies.  Of these patients, 77 percent and 79 percent of patients were refractory to Revlimid in the pomalidomide and pomalidomide plus dexamethasone groups, respectively, while 73 percent and 69 percent were refractory to Velcade, respectively; 61 percent and 59 percent, respectively, were refractory to both.

Over the course of the trial, patients received 4 mg of pomalidomide daily for the first three weeks of a four-week treatment cycle. In addition, half of the patients received 40 mg of dexamethasone weekly. All patients received daily low-dose aspirin.

Patients in the pomalidomide only treatment group whose disease worsened during the trial (56 percent) were switched to the pomalidomide plus dexamethasone treatment group.

Results showed that 34 percent of patients in the pomalidomide plus dexamethasone group achieved at least a partial response to treatment, compared to 13 percent of patients in the pomalidomide only group. The complete response rates were the same in both treatment groups (1 percent).

The median duration of response was 7.7 months with pomalidomide plus dexamethasone and 8.3 months with pomalidomide alone.

The median progression free survival was 4.7 months and 2.7 months for the two regimens, respectively. Median overall survival was 16.9 months and 14 months, respectively.

For patients refractory to both Revlimid and Velcade, 30 percent achieved a partial response or better with pomalidomide plus dexamethasone and 16 percent with pomalidomide alone.

As mentioned earlier, these results have been highlighted by many myeloma specialists and analysts as particularly noteworthy.

The median progression free survival for Revlimid- and Velcade-refractory patients was 3.9 months for pomalidomide plus dexamethasone and 2.0 months for pomalidomide alone; median overall survival was 13.7 and 12.7 months for the two regimens, respectively.

The most common severe side effects for both pomalidomide plus dexamethasone or pomalidomide alone were low white blood cell counts (38 percent and 45 percent of patients, respectively), low platelet counts (19 percent and 21 percent, respectively), low red blood cell counts (21 percent and 17 percent, respectively), pneumonia (19 percent and 8 percent, respectively), and fatigue (10 percent and 8 percent, respectively).

The researchers did not observe any cases of severe peripheral neuropathy, a complication characterized by pain and tingling in the extremities due to nerve damage. Peripheral neuropathy is frequently observed with thalidomide and Velcade treatment.

Six percent and 12 percent of patients in the pomalidomide plus dexamethasone group and the pomalidomide only group discontinued therapy due to side effects, respectively.

Final Phase 2 Results From Large French Study Of Pomalidomide and Dexamethasone In Patients With Refractory Myeloma

Dr. Xavier Leleu from the University Hospital inLille, France, presented the final results of a Phase 2 clinical trial that demonstrate that pomalidomide in combination with dexamethasone is active and well tolerated in relapsed/refractory myeloma patients heavily pre-treated with both Velcade and Revlimid.

Dr. Leleu pointed out that this study provides further evidence that pomalidomide has no cross resistance with Revlimid and that it can provide benefit for patients who have relapsed after other novel therapies.

The interim results of this study were presented at ASH last year (see related Beacon news).

A total of 84 patients were enrolled in the study, with a median age of 60 years. The median number of prior therapies was five, with all patients previously receiving Velcade and Revlimid.

Among the study participants, 43 received 4 mg of pomalidomide daily on days 1 through 21 of a 28-day treatment cycle and 41 received 4 mg of pomalidomide daily on all days of a 28-day treatment cycle. In addition, all patients received 40 mg of oral dexamethasone weekly.

The share of patients achieving a partial response or better was 35 percent for patients receiving 21 days of treatment and 34 percent in patients receiving 28 days of treatment.

The median progression-free survival was 6.3 months in both groups, and the median duration of response was 11.4 months and 7.9 months in patients receiving 21 and 28 days treatment, respectively.

Phase 2 Clinical Trial of Pomalidomide In Combination With Clarithromycin And Dexamethasone In Relapsed or Refractory Myeloma Patients

Dr. Tomer Mark from the Weill Cornell Medical College in New York presented results of a Phase 2 clinical trial that demonstrate that pomalidomide in combination with clarithromycin (Biaxin) and dexamethasone is efficacious and well tolerated in myeloma patients who relapsed following or were refractory to Revlimid treatment.

Dr. Mark pointed out that time to response was rapid, with patients achieving a partial response within a median of 1.5 treatment cycles. He concluded that the regimen is highly effective for heavily pretreated myeloma patients, particularly for patients who progressed after Revlimid therapy.

Clarithromycin is an antibiotic used to treat several bacterial infections. Previous research has shown that clarithromycin can improve the anti-myeloma activity of Revlimid and dexamethasone in first-line myeloma therapy. Dr. Mark and his colleagues hypothesized that clarithromycin might similarly enhance the activity of pomalidomide and dexamethasone in myeloma patients who relapsed following or were refractory to Revlimid treatment.

A total of 52 patients were enrolled in the study. They had received a median of five prior lines therapy, one of which was Revlimid.

Patients received 500 mg of clarithromycin twice daily, 40 mg of dexamethasone on days 1, 8, 15, and 22; and 4 mg of pomalidomide on days 1 to 21 of a 28-day cycle. Patients were also given aspirin to prevent blood clots.

Forty-six patients were eligible for analysis. They received a median of six treatment cycles.

Sixty percent of patients achieved at least a partial response after treatment with the combination regimen, with 7 percent of the patients achieving a stringent complete remission and another 20 percent achieving a very good partial response.

The median progression-free survival time was 8.2 months.

After a median follow up time of 9.4 months, 85 percent of patients were still alive.

A Phase 1/2 Study of Pomalidomide In Combination With Cyclophosphamide And Prednisone In Relapsed And Resistant Myeloma Patients

Dr. Antonio Palumbo from the University of  Torino in Italy presented the results from a Phase 1/2 clinical trial investigating the safety and efficacy of pomalidomide in combination with cyclophosphamide (Cytotoxan) and prednisone in patients with relapsed/refractory multiple myeloma.

According to Dr. Palumbo, pomalidomide plus cyclophosphamide and prednisone showed high response rates with limited side effects in patients with relapsed/refractory multiple myeloma, including patients who are resistant (refractory) to Revlimid.

A total of 41 patients were enrolled in the study, with a median age of 69 years. All patients had received prior Revlimid and had relapsed or had myeloma refractory to Revlimid. Patients had a received a median of three prior treatment regimens.

During the Phase 1 part of the trial, patients received one of four pomalidomide doses (1 mg, 1.5 mg, 2 mg, or 2.5 mg) daily during a 28-day treatment cycle.  In addition, they received cyclophosphamide (50 mg every other day, days 1 through 28) and prednisone (50 mg every other day, days 1 through 28), for a total of six cycles. In order to prevent blood clots, patients were also administered aspirin and, in some cases, heparin.

The dose testing in the Phase 1 part of the trial established 2.5 mg per day as the target dose of pomalidomide to be tested in the Phase 2 part of the trial.

Of the 29 evaluable patients in the Phase 2 part of the trial, at least 66 percent achieved a partial response as their best response to the combination regimen. This included a complete response in 7 percent, a very good partial response in 21 percent, and a partial response in 38 percent.

Among patients refractory to Revlimid, partial response or better was achieved in 81 percent of patients, including a complete response in 9 percent of patients, a very good partial response in 18 percent, and a partial response in 54 percent.

The most common severe side effects were low white blood cell counts (41 percent of patients), low platelet counts (10 percent), rash (10 percent), and neurologic problems (7 percent).

Long-Term Outcomes of Pomalidomide and Dexamethasone in Patients with Relapsed Multiple Myeloma

A poster presentation by researchers from the Mayo Clinic discussed the long-term efficacy and safety of pomalidomide in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma patients.

The presentation drew on results gathered over a period of four years since the first group of patients at the Mayo Clinic began to be treated with pomalidomide and dexamethasone.

Patients in the study had to have relapsed after at least one, but not more then three, prior treatments for their myeloma.  The pomalidomide-dexamethasone regimen consisted of 2 mg of pomalidomide given every day and 40 mg of dexamethasone administered once a week.

The overall response to treatment was 65 percent, including 7 percent stringent complete response, 7 percent complete response, 25 percent very good partial response, and 27 percent partial response.

Half of the patients responded within a rapid 1.7 months, and half responded for more than 21.3 months.

Ninety-one percent of the patients in the study were still alive one year after entering the trial, and 76 percent were alive after two years. Median overall survival has not yet been reached after a median follow-up of about 34 months.

The researchers also noted that standard-risk patients appear to perform better on the combination treatment than higher-risk patients, and the researchers concluded that the treatment is “highly effective” and “well-tolerated.”

For more information, please see abstracts 634, 812, 635, 632, and 2942 (respectively) on the ASH meeting website.