Results from many important multiple myeloma studies were presented this morning during the third day of the American Society of Clinical Oncology (ASCO) annual meeting.  Most of the talks were about potential new anti-myeloma drugs.

This update will summarize the presentations about carfilzomib ^[1] (Kyprolis ^[2]) and pomalidomide ^[3] (Pomalyst ^[4]), two of the most promising new treat­ments being developed for multiple myeloma.  Both of these drugs have been submitted to the U.S. Food and Drug Administration for potential approval as new myeloma treat­ments.

Carfilzomib

The first three presentations were about car­filz­o­mib.  Like Velcade ^[5] (bor­tez­o­mib), car­filz­o­mib belongs to the class of drugs known as proteasome inhibitors.

The session started with a presentation by Dr. Philippe Moreau from the University Hospital in Nantes, France.  Dr. Moreau presented results from a Phase 1/2 clinical trial testing car­filz­o­mib in com­bi­na­tion with melphalan ^[6] (Alkeran) and prednisone ^[7] in elderly newly diagnosed multiple myeloma patients (abstract ^[8]).

The goal of the study was to identify the best dose for car­filz­o­mib when used in this com­bi­na­tion.  Among the 24 patients included in Phase 1 of the trial, the maximum tolerated dose was 36 mg/m² of car­filz­o­mib.

An addi­tional 16 patients were enrolled in Phase 2 of the trial.  Among the 35 patients in both phases of the trial who were evaluated for response, the over­all response rate was 89 per­cent, with 3 per­cent achieving a complete response, 40 per­cent achieving a very good partial response, and 46 per­cent a partial response.

The second presentation was by Dr. Joseph Mikhael from the Mayo Clinic in Scottsdale, Arizona.  He presented results from the Phase 2 portion of a Phase 1/2 trial testing a regi­men known as “CYCLONE.” The regi­men consists of car­filz­o­mib in com­bi­na­tion with cyclophosphamide ^[9] (Cytoxan), thalidomide ^[10] (Thalomid), and dexamethasone ^[11] (Decadron) (abstract ^[12]).

Twenty-seven newly diagnosed myeloma patients eligible for stem cell trans­plan­ta­tion were enrolled in the study.  Among the 24 patients evaluated for response, the over­all response rate was 96 per­cent.  Specifically, 29 per­cent achieved a complete response, 46 per­cent a very good partial response, and 21 per­cent a partial response.

The most common severe side effects were fatigue, low white blood cell counts, blood clots, and muscular weakness.  Additionally, 29 per­cent developed mild periph­eral neu­rop­athy (pain, tingling, or loss of sensation in the extremities, and a common side effect of Velcade).

Dr. Jakubowiak from the University of  Chicago gave the final presentation about car­filz­o­mib.  He presented long-term follow-up results from a Phase 1/2 study of car­filz­o­mib in com­bi­na­tion with Revlimid ^[13] (lena­lido­mide) and low-dose dexa­meth­a­sone (abstract ^[14]).

Fifty-three newly diagnosed myeloma patients were included in the study.  Patients could enroll in the study regardless if they were trans­plant eligible or ineligible.

Thus far, 98 per­cent of patients have responded to the treat­ment.  Forty two per­cent have achieved a stringent complete response, and an addi­tional 20 per­cent have achieved a near complete response.  Among the 22 patients who achieved a complete response, 91 per­cent had no evidence of residual disease.

The pro­gres­sion-free survival rate was 97 per­cent at one year and 92 per­cent at two years.

Among patients who received more than eight cycles of the com­bi­na­tion ther­apy, the most common side effects were low white blood cell counts and fatigue.  Dr. Jakubowiak reported that periph­eral neu­rop­athy was limited, with 11 per­cent of patients experiencing mild or mod­er­ate neu­rop­athy.

In a presentation that also took place during this morning's session, Dr. Robert Orlowski of the M.D. Anderson Cancer Center reviewed the three car­filz­o­mib studies.  During his talk, he said that the three studies showed attractive response rates and, in some cases, deeper responses than in com­parable pre­vi­ous trials that used Velcade instead of car­filz­o­mib.

In addi­tion, car­filz­o­mib may offer a better side effect profile than Velcade.  However, Dr. Orlowski believes future comparisons between the two drugs should account for the fact that Velcade is increasingly being admin­istered sub­cu­tane­ously and just once a week, which noticeably improves its side effect profile.  (As a courtesy to The Beacon's readers, Dr. Orlowski has made his presentation ^[15] (PowerPoint format) available for download and viewing.)

Pomalidomide

Later in the session, Dr. Ravi Vij from Washington University School of Medicine in St. Louis presented results from a Phase 2 study of poma­lido­mide for advanced myeloma patients (abstract ^[16]).

The study included 221 re­lapsed and refractory myeloma patients with a median of five pre­vi­ous lines of ther­apy.  Half were treated initially with poma­lido­mide alone, while the other half were treated with poma­lido­mide plus low-dose dexa­meth­a­sone.  Results from the trial were presented last year at the American Society of Hematology meeting (see related Beacon ^[17] news).

Today, Dr. Vij presented an analysis of out­comes of the patients treated with poma­lido­mide and low-dose dexa­meth­a­sone who were refractory (resistant) to pre­vi­ous treat­ment with Revlimid, Velcade, or both.  Seventy-seven per­cent were refractory to Revlimid, 73 per­cent to Velcade, and 61 per­cent to both.  Additionally, 42 per­cent were refractory to both and also had received a stem cell trans­plant.

Among these patients, 20 per­cent achieved at least a partial response, median pro­gres­sion-free survival was 3.5 months, and the one-year survival rate was 59 per­cent.  These out­comes were similar regardless of whether patients were refractory to Revlimid or Velcade, both, or had a pre­vi­ous trans­plant.

Dr. Vij said that these results suggest that patients resistant to Revlimid will not necessarily be resistant to poma­lido­mide, despite that the two drugs are chemically related to one another.

Dr. Vij has made his presentation available ^[18] to The Beacon as a courtesy to the Beacon's readers.

Myeloma presentations from today and the rest of the ASCO meeting will be summarized in addi­tional ASCO daily updates.  Further 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 ^[19] coverage.