Yesterday was the second day of the 2012 American Society of Hematology (ASH) annual meeting.  Although the myeloma-related sessions got a bit of a late start, the day featured a wide range of interesting presentations about multiple myeloma.

Many myeloma-related oral presentations were given in the afternoon and were summarized in updates published yesterday and earlier today.

During the evening yesterday, a poster session took place where important new research findings were summarized in posters displayed throughout a large conference hall. The studies covered a variety of myeloma-related topics, ranging from new treatments being developed for myeloma, to stem cell transplantation, to chromosomal abnormalities, and much more.

New Treatments

One poster summarized the results of an Italian study that evaluated the efficacy and safety of Muphoran (fotemustine) in combination with Velcade (bortezomib) and dexamethasone (Decadron) in relapsed and refractory multiple myeloma patients (abstract). Muphoran is currently approved for the treatment of metastatic melanoma in certain European countries.

The Phase 1/2 study included 24 patients with a median age of 69 years. The patients had received a median of two prior therapies.

Patients received 80 mg/m² to 100 mg/m² of Muphoran on the first day of each 35-day treatment cycle.

The results showed that 62 percent of patients responded to the treatment, with 8 percent achieving a complete response, 33 percent a very good partial response, and 21 percent a partial response.

After a median follow-up time of 24 months, the median progression-free survival was 21 months and the median overall survival was 29 months.

The most common severe side effects included low platelet counts (45 percent of patients), infections (25 percent), peripheral neuropathy (pain and tingling in the extremities, 21 percent), and gastrointestinal symptoms (12 percent).

Results of a Phase 2 study of Circularly Permuted TRAIL (CPT) in combination with thalidomide (Thalomid) were also presented in a poster (abstract). CPT, which is being developed as a treatment for multiple myeloma and other blood cancers, activates receptors in the body called TRAIL that cause cells to die.  Preclinical studies have shown that CPT kills cancer cells but not most healthy cells.

This study included 43 myeloma patients who previously did not respond to thalidomide.  Overall, the patients had a median of four previous lines of therapy.

The patients in the study received between 5 mg/kg and 10 mg/kg of CPT on days 1 through 5 of a 21-day treatment cycle plus 100 mg of thalidomide every day.

Among the 41 patients who were evaluated for response, 22 percent responded to the combination therapy, with 5 percent achieving a complete response, 7 percent a near complete response, and 10 percent a partial response. Patients in the 10 mg/kg treatment group showed the highest response rate (27 percent).

The most common side effects included low white blood cell counts (47 percent), fever (35 percent), and elevated liver enzymes 33 percent).

Another poster presented the results of a Phase 1 study of alvocidib in combination with Velcade in relapsed and refractory multiple myeloma and non-Hodgkin’s lymphoma patients (abstract). Alvocidib belongs to a class of drugs called cyclin-dependent kinase inhibitors. Preclinical research has shown that alvocidib and Velcade act synergistically and lead to cell death in myeloma, leukemia, and lymphoma cells.

The study included 43 patients, 23 of whom had multiple myeloma. The median patient age was 65 years, and patients had received a median of three prior therapies.

The patients received 1.3 mg/m² of Velcade followed by between 15 mg and 90 mg of alvocidib on days 1, 4, 8, and 11 of 21-day treatment cycle.

Of the 38 patients evaluable for response, 34 percent of patients responded to treatment. Among the multiple myeloma patients evaluable for response, 35 percent responded, with 4 percent achieving a complete response and 31 percent a partial response.

The most common severe side effects included fatigue (60 percent), low platelet counts (56 percent), low white blood cell counts (47 percent), and diarrhea (47 percent).

Another poster showed the results of a study that evaluated the safety and efficacy of AR-42 in relapsed multiple myeloma and lymphoma patients (abstract). AR-42 belongs to a class of drugs called deacetylase (DAC) inhibitors.

The Phase 1 study included 17 patients who received 20 mg to 70 mg of oral AR-42 three times a week for three weeks in a 28-day treatment cycle.

The researchers observed dose-limiting side effects at the 50 mg dose, so 40 mg was defined as the maximum tolerated dose.

Minor responses were observed at the 40 mg dose level.

Based on the initial findings, the investigators recommend that AR-42 be further investigated in combination with other agents in Phase 1 trials for myeloma and T-cell lymphoma.

Pomalidomide

Yesterday’s poster session also included several studies about pomalidomide, a drug that is currently being reviewed by the U.S. Food and Drug Administration for approval for the treatment of multiple myeloma.

One of the posters showed additional results of a Phase 2 trial of pomalidomide plus dexamethasone in heavily pretreated multiple myeloma patients (abstract). Final results of the study had been presented at last year’s ASH annual meeting (see related Beacon news).

The study included 84 relapsed/refractory patients who had received a median of five prior therapies.  The median patient age was 60 years.

Patients received 4 mg of pomalidomide on days 1 through 21 or 1 through 28 of a 28-day treatment cycle.

Thirty-five percent for patients receiving 21 days of treatment and 34 percent of patients receiving 28 days of treatment responded.

The researchers found that the time to progression was longer (5 months) for the patients while taking pomalidomide, compared to the time to progression (4 months) on the last prior therapy before entering the study.

The difference was more pronounced in patients who responded: the time to progression had not been reached yet while on pomalidomide, compared to 26 months on the last prior treatment.

The researchers also found that overall survival was significantly longer for patients who responded to pomalidomide (not yet reached), compared to 13 months for patients with stable disease.

Another poster summarized the initial findings of an ongoing Phase 1/2 of pomalidomide in combination with dexamethasone and Doxil (doxorubicin liposomal) in relapsed and refractory myeloma patients.

Sixteen patients out of the planned 40 patients have been enrolled in the study so far.  They had received a median of four prior therapies.

Patients received between 2 mg and 4 mg of oral pomalidomide daily plus dexamethasone and Doxil.

Of the 10 patients evaluable for response, 40 percent have shown a partial response.

The most common side effects so far included low white blood cell counts (72 percent), low platelet counts (64 percent), and low sodium levels in the blood (63 percent).

Stem Cell Transplantation

A large number of posters during yesterday’s poster session were dedicated to research around stem cell transplantation.

One poster summarized the findings of a Phase 2 study that investigated the efficacy and safety of busulfan (Busulfex) plus Velcade in myeloma patients as an alternative to melphalan as part of a second transplant after relapse (abstract).

The study included 30 myeloma patients who had relapsed more than 12 months after their initial transplant. The median time between the first and second transplants was 28 months. The median patient age at the time of the second transplant was 59 years.  All patients had previously been treated with either Revlimid, thalidomide, or Velcade.

Patients received a test dose of 0.8 mg/kg of intravenous busulfan 9 to 12 days before the second stem cell transplant.  The investigators then calculated an individualized busulfan dose based on the patient’s response to the test dose.  The individualized dose was administered once daily on days 2 through 5 before the transplant.  In addition, the patients received a single dose of Velcade the day before the transplant.

At 60 days post transplant, 20 percent of patients responded to treatment, with 6 percent achieving a complete response and 14 percent achieving a very good partial response.

The most common severe side effects included low white blood cell counts with fever, mouth ulcers, and nausea.

Another poster showed the findings of an analysis that sought to determine the prognostic factors in myeloma patients who relapse early after stem cell transplantation (abstract).

The researchers analyzed data from two different datasets with information on 1,081 myeloma patients who underwent a stem cell transplant.  In both datasets, they found that approximately 20 percent of patients relapsed within 12 months. These patients also had short progression-free and overall survival times.

The researchers found that low red blood cell counts, low platelet counts, low albumin levels in the blood, beta-2 microglobulin levels of 5.5 mg/L or higher, and advanced myeloma combined with high-risk chromosomal abnormalities, such as t(4;14) and 1q21+, at the time of diagnosis were associated with early relapse.

The researchers then analyzed outcomes of second line treatment in the patients who relapsed early.

They found that patients who had a shorter remission after their second-line treatment than after the first transplant had particularly short progression-free and overall survival times.

According to the researchers, these patients have a particularly aggressive from of myeloma and should be assessed early for response after stem cell transplantation.

Another poster summarized the findings of a retrospective analysis that sought to define predictors for severe complications after stem cell transplantation (abstract). The investigators defined severe complications as those that required hospitalization of more than seven days or death.

The analysis included 190 patients who received an autologous stem cell transplant with melphalan between November 2008 and July 2011.  The median patient age was 58 years.

The investigators found that a melphalan dose of greater than 5 mg/kg, infusion of less than 3.5 billion stem cells/kg, and a loss of body weight of greater than 5 percent during initial treatment were associated with severe complications after the stem cell transplant.

Chromosomal Abnormalities

Several posters in this session covered research on chromosomal abnormalities.

One poster summarized findings of a retrospective analysis that evaluated the impact of the high-risk chromosomal abnormality del17p on outcomes in patients after stem cell transplantation (abstract).

The analysis was based on data from 226 myeloma patients who received an autologous stem cell transplant at the University of California, San Diego Moores Cancer Center between January 2000 and July 2011.

Of the 226 patients included in the analysis, 9 percent had del17p.

The researchers found that patients with del17p had similar complete response rates before (19 percent) and after the transplant (29 percent) as patient without chromosomal abnormalities (13 percent and 31 percent, respectively).

However, the progression-free and overall survival times (8 months and 48 months, respectively) were significantly shorter in patients with del17p than in those without (33 months and 68 months, respectively).

Myeloma presentations from Day 3 and Day 4 of the ASH 2012 meeting also will be summarized in ASH daily updates to be published at The Beacon the next few days.  Additional coverage of key research results from the meeting will continue throughout the rest of the week in individual, topic-specific news articles.  For all Beacon articles related to this year’s ASH meeting, see The Beacon’s full ASH 2012 coverage.