Tuesday was the final day of this year’s American Society of Hematology (ASH) meeting, which took place in Atlanta.  The meeting concluded in the morning with a series of oral presentation sessions held simultaneously.

Three of the morning sessions focused on the biology of multiple myeloma as well as preclinical and clinical studies of treat­ment options for multiple myeloma patients.

This update will summarize the research presented during the session that focused on myeloma treat­ment options.  In addi­tion, it will summarize results from an important late-breaking study of poma­lido­mide that also was presented Tuesday morning.

Half of the talks during the morning session on treat­ment options focused on new treat­ments for multiple myeloma.  The other half focused on important issues for myeloma patients, such as the risk of in­fec­tion, improvements in the survival of patients with kidney failure, and retreatment at relapse.

Treanda Plus Velcade And Dexamethasone

The first talk was given by Dr. Heinz Ludwig from Wilhelminen Hospital in Vienna.  Dr. Ludwig discussed results of a Phase 2 study of Treanda (bendamustine) in com­bi­na­tion with Velcade (bor­tez­o­mib) and dexa­methasone (Decadron) (abstract).

Treanda belongs to a class of drugs known as alkylating agents, which also includes melphalan (Alkeran) and cyclophosphamide (Cytoxan).  These drugs work by damaging the DNA of cancer cells, which in turn causes the cells to die.

Treanda is approved in a number of European countries to treat multiple myeloma in patients older than 65 years who are not eligible for stem-cell trans­plan­ta­tion and cannot be treated with thalidomide (Thalomid) or Velcade.  It is not yet approved in the United States as a treat­ment for multiple myeloma, but it is already approved by the U.S. Food and Drug Administration for the treat­ment of chronic lymphocytic leukemia and certain lym­phomas.

Treanda is marketed in the U.S. by Cephalon.  In Europe, the drug is sold under the brand names Ribomustin and Levact.

The study discussed by Dr. Ludwig included 79 myeloma patients with a median age of 64 years.  All patients had been treated with at least one prior ther­apy, with the majority of the patients (63 per­cent) having received one to two prior lines of ther­apy.

Among the 71 patients evaluated for response, 68 per­cent responded to the com­bi­na­tion ther­apy, with 21 per­cent achieving at least a near complete response, 16 per­cent a very good partial response, and 31 per­cent a partial response.  Among those pre­vi­ously treated with Revlimid (lena­lido­mide), 59 per­cent responded.

At a median follow-up of 13.7 months, median pro­gres­sion-free survival was 9.7 months.  The two-year over­all survival rate was 60 per­cent.

The most common severe side effects were low platelet counts (38 per­cent), low red blood cell counts (18 per­cent), and low white blood cell counts (17 per­cent).

Revlimid After Relapse

Dr. Meletios Dimopoulos from the University of Athens School of Medicine in Greece then discussed results of an analysis of the use of Revlimid in re­lapsed myeloma patients for patients who pre­vi­ously were re­lapsed after Revlimid-based treat­ment (abstract).

In particular, the analysis included patients from the MM-015 clinical trial conducted in Europe.  Participants in that trial were all at least 65 years of age and ineligible for stem cell trans­plan­ta­tion.  The patients were randomly selected to be given one of three sequences of treat­ment: mel­phalan-prednisone (MP) with no main­te­nance ther­apy afterwards; Revlimid-melphalan-prednisone (MPR) with no main­te­nance ther­apy afterwards; or MPR followed by Revlimid main­te­nance ther­apy (10 mg) (MPR-R).

Patients who progressed during the MM-015 trial could then receive further treat­ment with Revlimid (25 mg) or another treat­ment regi­men.  The choice of treat­ment at this point in time was left up to the patients and their treating physicians.

The results presented by Dr. Dimopoulos are based on a retrospective analysis of the trial out­comes.  The analysis compares the out­comes of the patients who were treated with Revlimid at relapse with those of patients treated with a regi­men that did not include Revlimid.

For each of the initial ther­apy regi­mens, patients treated with a Revlimid-based ther­apy at relapse tended to have a longer time between first and second relapse than patients treated with other drugs, including Velcade.

However, the advantage of using Revlimid at relapse -- instead of  other treat­ments -- was greatest among the patients who did not receive Revlimid main­te­nance ther­apy.

Overall, there was not much difference in the time between first and second relapse across the MP, MPR, and MPR-R patient groups.  Patients in the MPR-R group, which received Revlimid main­te­nance ther­apy, had the shortest time between first and second relapse (a median of 14 months).  This, though, was just a month or two less than the median for the other two groups of patients.

Infections And Multiple Myeloma

Next, Dr. Cecilie Blimark from the Sahlgrenska University Hospital in Gothenburg, Sweden, presented results from a study that evaluated the risk of in­fec­tion in myeloma patients compared to the general Swedish population.

The retrospective analysis included 9,610 multiple myeloma patients diagnosed between 1988 and 2004 as well as 37,718 matched controls from the general population.

Dr. Blimark reported that myeloma patients are 7.1 times more likely to develop an in­fec­tion than the general population.

The risk of in­fec­tion is particularly high within the first year after diag­nosis.  During that time, myeloma patients are 11.6 times more likely to develop an in­fec­tion than the general population.

Dr. Blimark and her colleagues also found that myeloma patients are especially more likely to develop septicemia, meningitis, and pneu­monia bacterial in­fec­tions as well as viral in­fec­tions.

The results also showed that in­fec­tions have become more prevalent over time in myeloma patients compared to the general population.

Dr. Blimark stated that an important question is whether modern myeloma ther­a­pies are increasing myeloma patients’ risk of developing in­fec­tions.  She concluded that new strategies are needed to fight and prevent in­fec­tion.

Kyprolis

Then Dr. Nikoletta Lendvai from Memorial Sloan-Kettering Cancer Center in New York City discussed results of a Phase 2 study investigating a slow, higher-dose infusion of Kyprolis (car­filz­o­mib) for re­lapsed and refractory myeloma patients (abstract; presentation slide deck (pdf) made available by Dr. Lendvai as a courtesy to the Beacon’s readers).

Previous studies showed that a slow infusion of Kyprolis allowed higher doses of the drug to be better tolerated.  So, in this study, Kyprolis was given via a 30 minute infusion at a dose of 56 mg/m², which is more than twice the dose recommended in the drug's FDA-approved pre­scrib­ing in­­for­ma­tion.

Patients in the study also were treated with low-dose dexa­meth­a­sone if they did not respond initially to treat­ment with Kyprolis alone.

The study included 41 patients with a median age of 63 years who had received a median of five prior lines of ther­apy.

Among the 38 patients evaluated for response, the over­all response rate was 53 per­cent, with 3 per­cent achieving a complete response, 24 per­cent a very good partial response, and 26 per­cent a partial response.

The median pro­gres­sion-free survival time was 7.6 months, and the one-year over­all survival rate was 50 per­cent.

The most common severe side effects were low platelet counts (37 per­cent), low red blood cell counts (20 per­cent), high blood pressure (20 per­cent), pneu­monia (15 per­cent), and fluid build-up in the lungs / chronic heart failure (10 per­cent).

In addi­tion, one of the 41 patients in the study died of lung failure which may have been the result of the Kyprolis treat­ment.

Improvements In Survival Of Myeloma Patients With Kidney Failure

Dr. Efstathios Kastritis from the Greek Myeloma Study Group in Athens, Greece, gave the last presentation of the morning session.  Her talk was about changes over time in the survival of myeloma patients with kidney failure (abstract).

The retrospective analysis included 1,773 myeloma patients treated in Greece since 1990.

The analysis found that, over the past 20 years, the median age of newly diagnosed myeloma patients has increased, but the rate of kidney failure among those patients has remained similar.

The survival of myeloma patients, in general as well as those with kidney failure, significantly improved over the timeframe analyzed.

Specifically, the researchers found that patients with kidney failure diagnosed after the introduction of novel agents beginning in 2000 -- and particularly those who were initially treated with novel agents -- had better over­all survival than other newly diagnosed myeloma patients with kidney failure.

However, the findings show that myeloma patients with severe kidney failure are two to four times more likely to die soon after diag­nosis, and this increased risk of early death has not improved over time.

Pomalidomide

In a separate session Tuesday morning dedicated to presentations about late-breaking research results, Dr. Meletios Dimopoulos of the University of Athens School of Medicine in Greece gave his second talk of the morning (abstract).

During this presentation, Dr. Dimopoulos reviewed results of an interim analysis of data from a Phase 3 trial involving 455 re­lapsed and refractory myeloma patients.  Half the patients in the trial were randomly selected to be treated with pomalidomide (Pomalyst) plus low-dose dexa­meth­a­sone.  The other half were treated with high-dose dexa­meth­a­sone alone.  Patients in the second group also could be treated with poma­lido­mide if their disease progressed, and about one third eventually were.

Highlights of the interim analysis have already been reported, both qualitatively and with some quantitative detail (see, respectively, this Beacon news article and the second item in this set of Beacon Newsflashes).

Pomalidomide is an immuno­modu­la­tory agent, meaning that it works by inducing a patient’s immune system to attack and destroy myeloma cells. It belongs to the same class of drugs as thalido­mide and Revlimid.

Pomalidomide is being developed by Celgene Corporation (NASDAQ: CELG), the same com­pany that markets Revlimid and thalido­mide in the United States and inter­na­tionally.

Patients in the trial discussed Tuesday by Dr. Dimopoulos had a median of five pre­vi­ous lines of ther­apy.  All patients had been pre­vi­ously treated with, and had stopped responding to, Revlimid.  Almost three quarters of the patients had also been treated with, and stopped responding to, Velcade.

During his talk, Dr. Dimopoulos reported that the over­all response rate, pro­gres­sion-free survival time, and over­all survival time were significantly higher among the patients treated with poma­lido­mide and low-dose dexa­meth­a­sone compared to the patients who received only high-dose dexa­meth­a­sone.

The over­all response rates were 21 per­cent in the poma­lido­mide and low-dose dexa­meth­a­sone group of patients versus 3 per­cent in the high-dose dexa­meth­a­sone patients.

Progression-free survival was 3.6 months and 1.8 months, respectively.

The median over­all survival has not yet been reached in the poma­lido­mide-dexamethasone patients.  It appears, however, that it will probably be almost twice the 7.8 months median over­all survival found in the patients treated with only dexa­meth­a­sone.

The most common severe side effects in the poma­lido­mide plus low-dose dexa­meth­a­sone and high-dose dexa­meth­a­sone patients were, respectively, low white blood cell counts (42 per­cent versus 15 per­cent), low red blood cell counts (27 per­cent versus 29 per­cent), in­fec­tions (24 per­cent versus 23 per­cent), and low platelet counts (21 per­cent versus 24 per­cent).

This article concludes The Beacon’s daily updates from ASH.  Summaries of the pre­vi­ous days’ presentations can be found in similar daily updates already published on The Beacon.  Additional coverage of key research results from the meeting will con­tinue the next several weeks 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.