This year’s American Society of Clinical Oncology (ASCO) annual meeting, which is being held in Chicago, began yesterday and goes through Tuesday.

The first of the myeloma-related sessions at this year's meeting began this morning with a poster session, in which important new research findings were summarized on posters throughout a large conference hall.

MLN9708

This morning’s session included two posters about MLN9708 (ixazomib), an oral drug that works similarly to Velcade (bor­tez­o­mib) and is being in­ves­ti­gated for the treat­ment of multiple myeloma as well as a number of other types of cancer.

The first poster included results from a Phase 1 trial of MLN9708, admin­istered once weekly as single ther­apy.  So far, the trial has included 52 patients with advanced myeloma (abstract), with a median of six pre­vi­ous lines of ther­apy.

Of the 52 patients, 8 per­cent have responded to treat­ment, with 2 per­cent (one patient) achieving a very good partial response, and 6 per­cent (three patients) achieving a partial response.  An addi­tional 23 per­cent of the patients achieved stable disease for at least some time, and 2 per­cent had a minimal response.

The maximum tolerated dose was 2.97 mg/m² of MLN9708.  The most common severe side effects were low platelet counts, diarrhea, fatigue, nausea, and low white blood cell counts.  In addi­tion, 12 per­cent of patients had mild or mod­er­ate periph­eral neu­rop­athy (pain, tingling, or loss of feeling in the extremities, and a common side effect of Velcade).

The second poster presented results from a Phase 1/2 study testing MLN9708 in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron) for pre­vi­ously untreated myeloma patients (abstract).

At the time the results were analyzed, 65 patients were enrolled in the study.  Of the 46 patients who have completed four or more treat­ment cycles, 98 per­cent have achieved at least a partial response to the treat­ment regi­men.   Specifically, 26 per­cent achieved a complete response, 20 per­cent achieved a very good partial response, and 52 per­cent a partial response.

Phase 1 of this study also determined 2.97 mg/m² to be the maximum tolerated dose of MLN9708.  The investigators recommended that a fixed dose of 4 mg be used for Phase 2 of the trial.

The most common severe side effects of the com­bi­na­tion ther­apy were rash, nausea, and vomiting.  Additionally, 22 per­cent of patients experienced mild or mod­er­ate periph­eral neu­rop­athy, but there were no cases of severe periph­eral neu­rop­athy.  One patient died during the study after contracting viral pneu­monia.

Carfilzomib

Another poster analyzed results from a Phase 2b study of carfilzomib (Kyprolis), a new agent that also works similarly to Velcade and is cur­rently being reviewed by the U.S. Food and Drug Administration for the treat­ment of multiple myeloma.

The analysis (abstract) included patients with advanced disease, specifically those who were either intolerant or refractory (resistant) to Velcade as well as Revlimid or thalidomide (Thalomid) (228 patients, referred to here as “double refractory/intolerant”) and a subgroup of those who were refractory to all approved classes of myeloma treat­ments (44 patients).  Across all patients in the study, the median time since diag­nosis was 5.4 years.

The results show that patients refractory to prior myeloma ther­a­pies had responses similar to the entire group of 266 patients included in the study.  Specifically, over­all response rates were 23 per­cent over­all, 21 per­cent for those who were double refractory/intolerant, and 20 per­cent for those refractory to all classes of myeloma ther­a­pies.  Responses lasted 7.8 months for the entire study group, 7.4 months for the double refractory/intolerant group, and 7.8 months for those refractory to all classes of treat­ment.

Pomalidomide

Results from a Phase 2 study of pomalidomide in com­bi­na­tion with clarithromycin (Biaxin) and dexa­meth­a­sone were also presented during the session (abstract).  Pomalidomide is chemically related to Revlimid and thalido­mide, and it is cur­rently being reviewed by the U.S. Food and Drug Administration for the treat­ment of multiple myeloma.

All 73 patients in the study had re­lapsed or refractory myeloma, with a median of five pre­vi­ous lines of ther­apy.  All had pre­vi­ously been treated with Revlimid.

Among the 66 patients evaluated for response, the over­all response rate was 56 per­cent.  Specifically, 5 per­cent achieved a stringent complete response, 17 per­cent a very good partial response, and 33 per­cent a partial response.

After a median follow-up of 1 year, 42 per­cent of patients had not progressed (median pro­gres­sion-free survival was 5 months) and 85 per­cent were alive.

Being refractory to Revlimid, Velcade, or double refractory did not appear to impact response or pro­gres­sion-free survival.

Metronomic Therapy

Another poster presented results from a retrospective study investigating the use of metronomic ther­apy for heavily pretreated myeloma patients (abstract).  Metronomic ther­apy is continuous or frequent treat­ment with low doses of anticancer ther­apy.  It is commonly used for many solid tumor cancers.

Researchers from the University of Arkansas analyzed data from 187 very advanced myeloma patients.  The patients were treated from 2004 to 2012 with metronomic ther­apy using a com­bi­na­tion of Velcade, thalido­mide, dexa­meth­a­sone, doxorubicin (Adriamycin), cisplatin, and Rapamune (rapamycin or sirolimus).

Overall, 49 per­cent responded to the metronomic ther­apy, with 6 per­cent achieving a complete response, 7 per­cent a very good partial response, and 36 per­cent a partial response.

The median pro­gres­sion-free survival time was 3.7 months, and the median over­all survival time was 1.1 years.

Almost all patients (95 per­cent) were treated in the outpatient setting, with 20 per­cent requiring hospi­tal­iza­tion at some point due to side effects.

Impact of Chromosomal Abnormality t(11;14)

Another poster included results from a retrospective analysis of myeloma patients who received a stem cell trans­plant.  The analysis compared out­comes of patients who had the chromosomal ab­nor­mal­ity t(11;14) to those with no chromosomal ab­nor­mal­i­ties (abstract).

The analysis included 1,239 patients who were treated between 2000 and 2010 at the M.D. Anderson Cancer Center in Texas .  Of these patients, 70 per­cent had no chromosomal ab­nor­mal­i­ties, 2 per­cent had t(11;14), and 28 per­cent had other chromosomal ab­nor­mal­i­ties.

When the researchers compared data for patients with t(11;14) to those without chromosomal ab­nor­mal­i­ties, they did not find any statistical differences between time from diag­nosis to stem cell trans­plan­ta­tion, disease status at time of trans­plan­ta­tion, or response after trans­plan­ta­tion for the two groups.

However, pro­gres­sion-free and over­all survival times were significantly shorter for patients with t(11;14).  Median pro­gres­sion-free survival times were 15.7 months for those with t(11;14) and 35.9 months for those with normal chromosomes.  Overall survival times were 51.4 months for those with t(11;14) and 88.4 months for those with normal chromosomes.

Secondary Cancers

Two studies about myeloma patients and second cancers were presented during the poster session.

The first was an analysis of data from a U.S.-based observational registry of multiple myeloma patients (abstract).  Preliminary results show that out of 1,175 patients analyzed, 15 patients (1.7 per­cent) developed a second cancer within a median of 6.5 months of beginning treat­ment for myeloma.  The patients who developed second cancers were pre­vi­ously treated with a variety of myeloma ther­a­pies, leading the investigators to conclude that "a causal rela­tion­ship with any single drug or regi­men is difficult to establish."

The second was a retrospective analysis of myeloma patients who underwent stem cell trans­plan­ta­tion (abstract) from 1989 to 2009 at the City of Hope National Medical Center in California.  Out of the 841 myeloma patients included in the analysis, 60 patients developed a total of 70 second cancers.  The over­all risk of developing a second cancer was 7.4 per­cent at 5 years and 15.9 per­cent at 10 years.  For patients over 65 years, the risk was 21.9 per­cent at 10 years.

Among the drugs the patients were treated with, only cumulative thalido­mide exposure appeared to possibly increase the risk of developing a second cancer.  Revlimid was not included in the researchers' analysis because there were not enough Revlimid-treated patients in their data.

However, given that several pre­vi­ous studies have shown that Revlimid increases a patient’s risk of developing a second cancer -- particularly in patients undergoing stem cell trans­plan­ta­tion -- the investigators suggest that other drugs chemically related to Revlimid and thalido­mide may also increase a patient’s risk of developing a second cancer.

Myeloma presentations from later today, Day 3, and Day 4 of the ASCO 2012 meeting also will be summarized in ASCO 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 ASCO meeting, see The Beacon’s full ASCO 2012 coverage.