The afternoon sessions of the third day of the American Society of Hematology (ASH) 2011 annual meeting in San Diego were just as awash with myeloma-related presentations as were the morning sessions.

Many of the afternoon sessions were devoted to two particular potential new myeloma treat­ments: car­filz­o­mib and pomalidome.

Those presentations will be covered in this article, while presentation from the afternoon sessions that were about other new ther­a­pies will be summarized in the final daily update for the meeting's third day.

Carfilzomib

Carfilzomib ^[1] (Kyprolis ^[2]) is an investigational drug that belongs to the same class of myeloma treat­ments as Velcade ^[3] (bor­tez­o­mib).

Onyx Pharmaceuticals, the com­pany developing car­filz­o­mib, has applied to the U.S. Food and Drug Administration for approval to market car­filz­o­mib in the United States as a treat­ment for re­lapsed and refractory myeloma.  A decision on that application is expected by the end of July 2012 (see related Beacon ^[4] news).

During the first talk in the afternoon, Dr. Andrzej Jakubowiak of the University of Chicago presented results from a Phase 1/2 study of car­filz­o­mib in com­bi­na­tion with Revlimid ^[5] (lena­lido­mide) and low-dose dexamethasone ^[6] (Decadron) in pre­vi­ously untreated multiple myeloma patients (abstract ^[7]).

The study included 53 patients with a median age of 59 years; 60 per­cent of study participants had advanced myeloma.

The patients received eight cycles of induction ther­apy with car­filz­o­mib, Revlimid, and dexa­meth­a­sone. After that, treat­ment was con­tinued as main­te­nance ther­apy at the doses tolerated at the end of eight cycles. Patients who had a partial response or better could receive a stem cell trans­plant after four treat­ment cycles.

Among the 49 patients assessed for response, 94 per­cent achieved at least a partial response, with 53 per­cent achieving a complete or stringent complete response. After 12 treat­ment cycles, 79 per­cent of patients achieved a near complete, complete, or stringent complete response.

Almost a quarter of the patients receiving the com­bi­na­tion treat­ment experienced periph­eral neu­rop­athy, a con­di­tion char­ac­ter­ized by pain and tingling in the extremities due to nerve damage. However, Dr. Jakubowiak pointed out that all cases were mild to mod­er­ate.

Dr. Jakubowiak closed his presentation by saying that this new treat­ment regi­men is highly active and well tolerated in newly-diagnosed multiple myeloma patients, with responses that compare favorably to those achieved with the best frontline regi­mens for myeloma.

Dr. Pieter Sonneveld from the Erasmus Medical Center in Rotterdam, The Netherlands, also presented results from a study of car­filz­o­mib in newly diagnosed myeloma patients.

This Phase 2 trial in­ves­ti­gated the efficacy and safety of car­filz­o­mib plus thalidomide ^[8] (Thalomid) and dexa­meth­a­sone as an induction ther­apy prior to stem cell trans­plan­ta­tion and as consolidation ther­apy after trans­plant (abstract ^[9]).

The study included 34 patients with a median age of 57 years; 63 per­cent of patients had advanced myeloma.

The patients received four cycles of induction ther­apy with car­filz­o­mib, thalido­mide, and dexa­meth­a­sone, then proceeded to stem cell trans­plan­ta­tion and con­tinued with four cycles of consolidation ther­apy with the car­filz­o­mib com­bi­na­tion.

After induction ther­apy, 84 per­cent of patients achieved at least a partial response, with 16 per­cent of patients achieving a complete response or stringent complete response, 29 per­cent a very good partial response, and 39 per­cent a partial response.

Eight patients have undergone a stem cell trans­plant so far, and four patients have completed consolidation ther­apy.

Twenty-four per­cent of patients experienced periph­eral neu­rop­athy; all cases were mild to mod­er­ate.

A third presentation on car­filz­o­mib was given by Dr. Ravi Vij from the Washington University School of Medicine in St. Louis.

Dr. Vij presented the final results of a Phase 2 study of single-agent car­filz­o­mib in re­lapsed/refractory myeloma patients who had not pre­vi­ously been treated with Velcade (abstract ^[10]; presentation slide deck ^[11] (pdf), made available by Dr. Vij as a courtesy to The Beacon's readers).

Patients received either 20 mg/m² of car­filz­o­mib for all treat­ment cycles or 20 mg/m² during the first cycle followed by 27 mg/m² for all sub­se­quent cycles.

The study included 129 patients with a median age of 65 years who had not been treated with Velcade before. Patients had received a median of two prior ther­a­pies.

The median duration of car­filz­o­mib treat­ment was seven cycles.

A total of 42 per­cent and 52 per­cent, respectively, of the two treat­ment groups achieved a partial response or better as their best response to treat­ment.

The median time to disease pro­gres­sion was 8.3 months and median duration of response was 13.1 months in the first treat­ment group. Both the median time to pro­gres­sion and the median duration of response have not been reached yet in the second treat­ment group.

Dr. Vij pointed out that the higher response rates in the second treat­ment group do not appear to be asso­ci­ated with higher side effects.

Treatment-related periph­eral neu­rop­athy was mild and infrequent (16 per­cent). Only one case of severe periph­eral neu­rop­athy was observed.

Dr. Vij concluded that single-agent car­filz­o­mib has shown durable activity in Velcade-naïve patients with re­lapsed multiple myeloma. In addi­tion, car­filz­o­mib was asso­ci­ated with limited periph­eral neu­rop­athy.

Pomalidomide

Four presentations about pomalidomide ^[12] (Pomalyst ^[13]) were given during the afternoon session.

Pomalidomide, which is being developed by Celgene, belongs to the same class of drugs as Revlimid and thalido­mide.  Many industry analysts expect poma­lido­mide to be approved as a new treat­ment for re­lapsed and refractory myeloma within the next one to two years.

The first poma­lido­mide-related presentation was given by Dr. Antonio Palumbo from the University of Torino in Italy (abstract ^[14]).

Dr. Palumbo presented results from a Phase 1/2 study of poma­lido­mide in com­bi­na­tion with cyclophosphamide ^[15] (Cytoxan) and prednisone ^[16] in patients with re­lapsed / refractory multiple myeloma.

The study included 41 patients with a median age of 69 years. All patients had pre­vi­ously received Revlimid and had re­lapsed or were refractory to Revlimid.   In addi­tion, all patients had one to three pre­vi­ous lines of therapy, with the median being three pre­vi­ous treat­ment regi­mens.

The dose testing in the Phase 1 part of the trial established 2.5 mg / day as the target dose of poma­lido­mide to be tested in the Phase 2 part of the trial

Of the 29 evaluable patients in the Phase 2 part of the trial, at least 66 per­cent achieved a partial response as their best response to the com­bi­na­tion regi­men.

The most common severe side effect was low white blood cell counts, which was observed in 40 per­cent of patients.  Otherwise, there was only a limited number of severe side effects.

Dr. Paul Richardson from the Dana-Farber Cancer Institute in Boston presented Phase 2 results from a Phase 1/2 study of poma­lido­mide alone versus poma­lido­mide plus low-dose dexa­meth­a­sone in re­lapsed / refractory multiple myeloma patients (abstract ^[17]; presentation slide deck ^[18] (pdf), made available by Dr. Richardson as a courtesy to The Beacon's readers).

In the Phase 1 part of the study, 4 mg / day was identified as the target dose for use during the Phase 2 part of the study.

In the Phase 2 part, all patients received 4 mg of poma­lido­mide daily on days 1 through 21 of 28-day treat­ment cycles. In addi­tion, half of the patients received 40 mg of dexa­meth­a­sone weekly.

A total of 221 patients were enrolled in the Phase 2 part of the trial.  Patients had a median of five pre­vi­ous lines of ther­apy, and a majority of patients had been treated with -- and stopped responding to -- both Revlimid and Velcade.

Results showed that 34 per­cent of patients in the poma­lido­mide plus dexa­meth­a­sone group achieved at least a partial response to treat­ment, compared to 13 per­cent of patients in the poma­lido­mide only group. The complete response rates were the same in both treat­ment groups (1 per­cent).

The median duration of response was 7.7 months with poma­lido­mide plus dexa­meth­a­sone and 8.3 months with poma­lido­mide alone.

The median pro­gres­sion free survival was 4.7 months and 2.7 months for the two regi­mens, respectively. Median over­all survival was a 16.9 months and 14 months, respectively.

The most common severe side effect in both arms of the Phase 2 part of the study was low white blood cell counts.

According to Dr. Richardson, the results indicate that both regi­mens are active and generally well tolerated in patients with advanced multiple myeloma. He also noted that poma­lido­mide plus dexa­meth­a­sone appears to be more active with no increase in side effects compared to poma­lido­mide alone.

Dr. Tomer Mark from the Weill Cornell Medical College in New York City presented the results from a Phase 2 trial of clarithromycin (Biaxin), poma­lido­mide, and dexa­meth­a­sone ther­apy in re­lapsed and refractory myeloma patients (abstract ^[19]).

Dr. Mark started his presentation by mentioning that pre­vi­ous research has shown that clarithromycin enhances the anti-myeloma activity of Revlimid and dexa­meth­a­sone in the upfront treat­ment of multiple myeloma. He and his colleagues therefore hypothesized that clarithromycin might similarly enhance the activity of poma­lido­mide and dexa­meth­a­sone in patients with re­lapsed/refractory meyloma after prior Revlimid ther­apy.

Fifty-two patients were enrolled in the study. Patients had a median of five prior lines of ther­apy, one of which was required to be Revlimid.

Forty-six patients were eligible for analysis. Patients received a median of six treat­ment cycles.

Sixty per­cent of patients achieved at least a partial response after treat­ment with the com­bi­na­tion regi­men, with 7 per­cent of the patients achieving a stringent complete remission and another 20 per­cent achieving a very good partial response.

Dr. Mark pointed out that time to response was rapid, with patients achieving a partial response within a median of 1.5 treat­ment cycles.

The median pro­gres­sion-free survival time was 8.2 months.

After a median follow up time of 9.4 months, 85 per­cent of patients were still alive.

Dr. Mark concluded that this com­bi­na­tion is a highly effective regi­men for heavily pretreated myeloma patients, particularly for patients who progressed after Revlimid ther­apy.

The final poma­lido­mide-related presentation was given by Dr. Xavier Leleu from the University Hospital in Lille, France.

Dr. Leleu presented the final results of a Phase 2 trial of poma­lido­mide in com­bi­na­tion with low-dose dexa­meth­a­sone in re­lapsed/refractory myeloma patients who were pre­vi­ously treated with Velcade and Revlimid (abstract ^[20]).

The study included 84 patients with a median age of 60. The median number of prior ther­a­pies was five. All patients had pre­vi­ously received Velcade and Revlimid.

Fourty-three patients in the trial received 4 mg of poma­lido­mide daily on days 1-21 of a 28-day treat­ment cycle, and another 41 patients received 4 mg of poma­lido­mide daily on all days of a 28-day treat­ment cycle. In addi­tion, all patients received 40 mg of oral dexa­meth­a­sone per week.

The share of patients achieving a partial response or better was 35 per­cent in the 21/28 treat­ment arm and 34 per­cent in the 28/28 treat­ment arm.

The median duration of response was 11.4 months and 7.9 months in the 21/28 and 28/28 arms of the trial, respectively.  The median pro­gres­sion-free survival was 6.3 months in both arms.

Dr. Leleu concluded that poma­lido­mide in com­bi­na­tion with dexa­meth­a­sone is active and well tolerated in these heavily pre-treated myeloma patients.