More than twenty presentations about studies involving Pomalyst were pre­sented at this year’s meeting of the American Society of Hematology (ASH), which took place last month.

Several of these presentations were about the Phase 3 clinical trial that found Pomalyst ^[1] (pomalidomide, Imnovid) plus low-dose dex­a­meth­a­sone ^[2] (Decadron) significantly improved overall survival of relapsed and re­frac­to­ry myeloma pa­tients compared to high-dose dex­a­meth­a­sone alone (see related Beacon ^[3] news).  This is the study that led to the ap­prov­al of pomalidomide in Europe, where it is marketed under the brand name Imnovid (see related Beacon ^[4] news).

Two of these ASH presentations discussed the final analysis of the Phase 3 study.  The others analyzed the findings of this study or Phase 2 studies of Pomalyst plus dex­a­meth­a­sone based on pa­tient char­ac­ter­istics, in­clud­ing older age, chro­mo­som­al abnormalities, or prior therapies.

Many of the other presentations were about studies of Pomalyst and dex­a­meth­a­sone in combination with a third drug, such as Velcade ^[5] (bortezomib), Kyprolis ^[6] (carfilzomib), Doxil ^[7] (doxorubicin liposomal), cyclo­phos­pha­mide ^[8] (Cytoxan), or clarithromycin ^[9] (Biaxin).

There were also several preclinical studies of Pomalyst that were presented at the meeting.  A list of all Pomalyst-related abstracts from the ASH meeting can be found here ^[10].

This ASH update will summarize the findings from the presentations about Pomalyst plus dex­a­meth­a­sone for the treatment of relapsed and refractory multiple myeloma.  A separate article will summarize findings from the Pomalyst-based three-drug combinations.

A key finding of the studies discussed below is that Pomalyst appears to be more effective in certain re­lapsed myeloma patients than previously thought.  In particular, myeloma patients with the del(17p) chro­mo­som­al abnormality, which generally is a marker of harder-to-treat ("higher-risk") disease, responded as well to Pomalyst as patients without any higher-risk chro­mo­som­al abnormalities.

Updated Results For Pomalyst Plus Low-Dose Dexamethasone Versus High-Dose Dexamethasone

During ASH, Dr. Meletios Dimopoulos from Alexandria Hospital in Athens (abstract ^[11]) and Dr. Jesús San Miguel from the University Hospital in Salamanca, Spain (abstract ^[12]), both presented final results from the Phase 3 study comparing treatment with Pomalyst plus low-dose dex­a­meth­a­sone to treatment with high-dose dex­a­meth­a­sone alone.

The study included 455 heavily pretreated multiple myeloma pa­tients.  Two-thirds of the pa­tients were treated with 4 mg of Pomalyst on days 1 to 21 plus low-dose dex­a­meth­a­sone (40 mg on days 1, 8, 15, and 22) of a 28-day cycle, while the remaining third received high-dose dex­a­meth­a­sone (40 mg on days 1 to 4, 9 to12, and 17 to 20) without any Pomalyst.

The median age was 64 years for those who received Pomalyst plus low-dose dex­a­meth­a­sone and 65 years for those who received high-dose dex­a­meth­a­sone alone.  Patients in both treatment groups had received a median of five prior lines of therapy.  All had received prior Revlimid ^[13] (lenalidomide) and prior Velcade therapy, 75 per­cent were refractory to both Revlimid and Velcade therapy, and 70 percent had undergone stem cell transplantation.

The median follow-up time was 15.4 months.

The overall re­sponse rate was significantly higher for pa­tients receiving Pomalyst plus low-dose dex­a­meth­a­sone compared to pa­tients receiving high-dose dex­a­meth­a­sone.  Among the pa­tients treated with Pomalyst, 32 percent responded, with 1 percent achieving a complete re­sponse, 6 percent a very good partial re­sponse, and 25 percent a partial re­sponse.  Among those treated with high-dose dex­a­meth­a­sone, 11 percent responded, with 1 percent achieving a very good partial re­sponse, and 10 percent a partial re­sponse.

The median duration of re­sponse was 7.5 months for those treated with Pomalyst plus low-dose dex­a­meth­a­sone and 5.1 months for those treated with high-dose dex­a­meth­a­sone.

Further analyses of the results showed that outcomes were better with Pomalyst plus low-dose dex­a­meth­a­sone treatment, compared to dex­a­meth­a­sone alone, regardless of prior treatment history.  In addition, time-to-progression while on Pomalyst treatment (4.6 months) was similar to time-to-progression on their last prior therapy 4.4 months).

The results showed that Pomalyst plus dex­a­meth­a­sone improved progression-free and overall survival.  The median progression-free survival was 4.0 months for those treated with Pomalyst and 1.9 months for those treated with dex­a­meth­a­sone alone.  Similarly, the median overall survival was 13.1 months for those treated with Pomalyst and 8.1 months for those treated with dex­a­meth­a­sone alone.

Pomalyst Plus Low-Dose Dexamethasone For High-Risk Myeloma

Dr. Dimopoulos and, in a separate presentation, Dr. Xavier Leleu from the Hopital Claude Huriez in Lille, France (abstract ^[14]), also presented results demonstrating the efficacy of Pomalyst plus low-dose dex­a­meth­a­sone in pa­tients with the high-risk chro­mo­som­al abnormalities del(17p) and t(4;14).

In particular, they showed that Pomalyst and low-dose dex­a­meth­a­sone appeared to have almost the same efficacy in pa­tients with the del(17p) chro­mo­som­al abnormality as in pa­tients without either the t(4:14) or del(17p) abnormality.

In the Phase 3 study discussed by Dr. Dimopoulos, the median progression-free survival of pa­tients treated with Pomalyst and low-dose dex­a­meth­a­sone was 4.2 months for pa­tients without either of the two high-risk abnormalities, 4.6 months for pa­tients with the del(17p) abnormality, and 2.8 months for pa­tients with the t(4;14) abnormality.

The median overall survival of pa­tients treated with Pomalyst and low-dose dex­a­meth­a­sone was 14.0 months for pa­tients without either of the two high-risk abnormalities, 12.6 months for pa­tients with the del(17p) abnormality, and 7.5 months for pa­tients with the t(4;14) abnormality.

Results from the multicenter Phase 2 trial that Dr. Leleu presented showed similar findings.  The study included 50 relapsed and refractory multiple myeloma pa­tients who had del(17p) and/or t(4;14).  The median pa­tient age was 63 years, and the patients had received a median of three prior lines of therapy.

The overall re­sponse rate was 22 percent; 32 percent for pa­tients with del(17p) and 16 percent for pa­tients with t(4;14). The median time-to-progression was 2.9 months: 7.3 months for del(17p) and 2.8 months for t(4;14).  The median overall survival was 12 months: 12 months for del(17p) and 9.2 months for t(4;14).

Taken together, the findings from these two studies indicate that Pomalyst is more effective for myeloma pa­tients with the del(17p) chro­mo­som­al abnormality than was previously realized.

Pomalyst Plus Low-Dose Dexamethasone For Older Myeloma Patients

Another analysis of the Phase 3 study showed that Pomalyst plus low-dose dex­a­meth­a­sone is beneficial for relapsed and refractory myeloma pa­tients over the age of 65 years (abstract ^[15]; full poster ^[16] [PDF]).

The results for pa­tients over the age of 65 were similar to those for pa­tients aged 65 or younger; pa­tients who received Pomalyst plus low-dose dex­a­meth­a­sone had higher re­sponse rates and longer progression-free and overall survival than pa­tients who received high-dose dex­a­meth­a­sone.

According to the investigators, their findings support considering Pomalyst plus low-dose dex­a­meth­a­sone as a standard treatment option for relapsed and refractory myeloma pa­tients regardless of age.

Effect Of Prior Revlimid Or Thalidomide Therapy On Pomalyst Therapy

An analysis of another Phase 2 study looked at how prior Revlimid or thalidomide ^[17] (Thalomid) therapy affected re­sponse to Pomalyst plus dex­a­meth­a­sone (abstract ^[18]).

This is an important issue because Pomalyst is in the same general class of drugs – known as immuno­mod­u­la­tory agents – as Revlimid and thalidomide.  Typically, myeloma specialists do not expect a drug to be as effective in patients previously treated with other drugs in the same class.

Among the 208 pa­tients included in the Phase 2 study, the median number of prior therapies was three; 91 percent had previously been treated with Revlimid or thalidomide, and 39 percent had received Revlimid or thalidomide as their last treatment prior to Pomalyst therapy.

The results show that pa­tients whose last line of therapy contained Revlimid or thalidomide were less likely to respond to Pomalyst (29 percent re­sponse rate compared to 44 percent for those who did not receive either of these drugs in their last line of therapy).  Their median duration of treatment was also shorter (5.7 months versus 7.3 months).

Among those previously treated with Revlimid or thalidomide at any point, those who had a shorter duration of Revlimid or thalidomide treatment and those who had more time between Revlimid/thalidomide treatment and start of Pomalyst treatment were more likely to respond to Pomalyst.