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

On the first day of the meeting, there was only one talk related to multiple myeloma.  During an afternoon education session, in which current practice and recent research results are reviewed, Dr. Raphael Fonseca from the Mayo Clinic in Scottsdale, Arizona, spoke about high-risk multiple myeloma.

The second day of the meeting included a morning and an afternoon session in which myeloma researchers presented their findings in the form of posters.

The highlights from the morning poster session included four Phase 2 studies on carfilzomib ^[1], a new agent being studied for the treat­ment of multiple myeloma.  Carfilzomib works similarly to Velcade ^[2] (bor­tez­o­mib) but appears to cause less periph­eral neu­rop­athy (pain and tingling in the extremities).  It is expected to be approved by the U.S. Food and Drug Administration for use in the United States by the end of the year.

The first study, a Phase 2 clinical trial in re­lapsed / refractory multiple myeloma patients, showed that the com­bi­na­tion of car­filz­o­mib, Revlimid ^[3] (lena­lido­mide), and low-dose dexamethasone ^[4] (Decadron) is effective and that the side effects of the com­bi­na­tion are tolerable (abstract ^[5]).  The over­all response rate was 78 per­cent (24 per­cent complete or near complete response, 18 per­cent very good partial response, and 37 per­cent partial response).  Most patients responded within the first two months of treat­ment, but responses improved with longer treat­ment.  The most severe side effects were primarily low blood cell counts.  Fatigue and diarrhea were also common.  A Phase 3 study comparing this com­bi­na­tion versus Revlimid and dexa­meth­a­sone alone opened in July and is recruiting patients.

An ongoing Phase 2 study presented during the poster session is evaluating the efficacy of car­filz­o­mib in patients with re­lapsed myeloma who have never before been treated with Velcade (abstract ^[6]). Two dosing regi­mens were used.  Higher dosing yielded better results.  For patients receiving the higher dosing, the over­all response rate was 51 per­cent (26 per­cent very good partial response, 25 per­cent partial response).  The median duration of response was 13.1 months for the lower dosing and not yet reached at 10.3 months follow-up time for the higher dosing.  Like the pre­vi­ous study, the main serious side effects were low blood cell counts.  Fatigue, nausea, and shortness of breath were also common.  While on ther­apy, around 16 per­cent of participants developed mild periph­eral neu­rop­athy and one case of severe neu­rop­athy was reported.

A long-term follow-up analysis from a Phase 2 study of car­filz­o­mib in patients with advanced re­lapsed / refractory multiple myeloma showed an over­all response rate of 24 per­cent (0.4 per­cent complete response, 5 per­cent very good partial response, 18 per­cent partial response) with a median duration of response of 7.8 months (abstract ^[7]).  Patients who had chromosomal ab­nor­mal­i­ties responded similarly with an over­all response rate of 30 per­cent and a median duration of response of 7 months. Velcade-refractory patients had an over­all response rate of 17 per­cent.  For the entire group of study participants, pro­gres­sion-free survival was 3.7 months and median over­all survival was 15.6 months.  Like the pre­vi­ous two studies, the main serious side effects were low blood cell counts, and new cases of periph­eral neu­rop­athy were uncommon.

Another Phase 2 study of car­filz­o­mib in re­lapsed / refractory multiple myeloma patients likewise showed that car­filz­o­mib-based ther­apy is effective in myeloma patients with very advanced disease (abstract ^[8]).  Carfilzomib was admin­istered in com­bi­na­tion with dexa­meth­a­sone, and other ther­a­pies could be added after the first cycle.  In this study, the over­all response rate was 37 per­cent (18 per­cent complete or near complete response, 19 per­cent partial response). Event-free survival was 21 per­cent at 6 months and 11 per­cent at 12 months.  Overall survival was 54 per­cent at 6 months and 42 per­cent at 12 months.  Almost all participants experienced low blood cell, high blood sugar, low potassium, and low phosphate levels; and most experienced fatigue.

The poster session concluded with a discussion of some of the posters.  Dr. Jonathan Kaufman from Emory University spoke about the first three car­filz­o­mib studies.  He was an investigator on two of the studies.

Dr. Kaufman said that all three studies dem­onstrate that car­filz­o­mib is effective in re­lapsed / refractory myeloma patients and that it is asso­ci­ated with low rates of periph­eral neu­rop­athy.  He said, however, that a number of questions remain:  What is the optimal dosing for car­filz­o­mib?  Does car­filz­o­mib, alone or in com­bi­na­tion, provide a survival advantage compared to the current standard of care?  How does the safety and efficacy of car­filz­o­mib compare to Velcade, especially now that weekly and sub­cu­tane­ous admin­istra­tion of Velcade have been shown to be safer?

There were two presentations from the afternoon session that may be of interest for myeloma patients.

The first study in­ves­ti­gated GDC-0941 ^[9], a new oral drug that is in the early stages of clinical testing.  The dosing of GDC-0941 was studied in this Phase 1 trial in patients with advanced solid tumors or multiple myeloma (abstract ^[10]).  Initial results in patients with solid tumors show that GDC-0941 is generally well tolerated below 450 mg daily.  Serious side effects included rash, fatigue, low white blood cell counts, and high blood sugar levels.  Common side effects included nausea, diarrhea, fatigue, vomiting, ab­nor­mal taste, and loss of appetite.  GDC-0941 appeared to have anti-tumor effects in several patients.  Results are not yet available for the study participants with multiple myeloma.

Results from a large Phase 3 trial comparing sub­cu­tane­ous Xgeva ^[11] (denosumab) with intravenous Zometa ^[12] (zoledronic acid) was also presented during the afternoon poster session.  Xgeva and Zometa are both used to treat cancer patients with bone disease.  This particular study included patients with bone metasteses from solid tumors or bone lesions due to multiple myeloma.  The results showed that patients receiving denosumab were 10 per­cent less likely to experience a skeletal-related event as compared to patients receiving Zometa.

For addi­tional summaries of the day’s sessions, see The Myeloma Beacon’s extensive Day 1 and Day 2 ^[13] coverage in the Beacon multiple myeloma forums ^[14].  News from the rest of the ASCO meeting will also be summarized in the forums and in daily updates like this one.