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 (Kyprolis) is an investigational drug that belongs to the same class of myeloma treat­ments as Velcade (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 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 (lena­lido­mide) and low-dose dexamethasone (Decadron) in pre­vi­ously untreated multiple myeloma patients (abstract).

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 (Thalomid) and dexa­meth­a­sone as an induction ther­apy prior to stem cell trans­plan­ta­tion and as consolidation ther­apy after trans­plant (abstract).

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; presentation slide deck (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 (Pomalyst) 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).

Dr. Palumbo presented results from a Phase 1/2 study of poma­lido­mide in com­bi­na­tion with cyclophosphamide (Cytoxan) and prednisone 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; presentation slide deck (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).

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).

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.