Tuesday was the last day of the American Society of He­ma­tol­ogy annual meeting in Orlando.  The myeloma portion of the conference concluded with one session of talks in the morn­ing about treat­ments under devel­op­ment.

The first talk was given by Dr. David Siegel of Hackensack Uni­ver­sity Medical Center in New Jersey.  Dr. Siegel pre­sented re­­sults from a study of single-agent carfilzomib ^[1] in myeloma patients who had re­lapsed mul­ti­ple times and did not respond to their last treat­ment (abstract ^[2]).

Among the 257 evaluable par­tic­i­pants, 24 per­cent achieved at least a partial re­sponse, 10 per­cent a minimal re­sponse, and 35 per­cent stable dis­ease.  Importantly, car­filz­o­mib was as ef­fec­tive in patients with un­fa­vor­able chromosomal ab­nor­mal­i­ties (28 per­cent achieved at least a partial re­sponse).

Patients responded to car­filz­o­mib for a median of 8.3 months, and median over­all sur­vival was 15.5 months.  Disease pro­gres­sion and sur­vival were both ­de­pen­dent on the patient’s re­sponse to treat­ment.  Better re­sponses corresponded with longer pro­gres­sion-free sur­vival and sur­vival.

Dr. Siegel said that there were “surprisingly few” blood-related side effects, par­tic­u­larly in terms of severe side effects  Twelve per­cent of patients devel­oped periph­eral neu­rop­athy (nerve damage to the extremities that can cause pain and tingling sensations), but less than 1 per­cent devel­oped severe neu­rop­athy.

Sixteen per­cent of patients com­pleted all 12 cycles of treat­ment.  The majority of patients who dis­con­tinued ther­apy did so because of dis­ease pro­gres­sion.  Nine per­cent of patients died on study, also mostly due to dis­ease pro­gres­sion.

Dr. Siegel concluded by saying he thought car­filz­o­mib is “an amazing new drug.”

Next, Dr. Paul Richardson from the Dana-Farber Cancer Center in Boston pre­sented a Phase 2 study of elotuzumab ^[3], a humanized mono­clonal anti­body (abstract ^[4]).  Elotuzumab was given in com­bi­na­tion with Revlimid ^[5] (lena­lido­mide) and low-dose dexamethasone ^[6] (Decadron) to re­lapsed/refractory mul­ti­ple myeloma patients who had not re­ceived prior Revlimid ther­apy.

A total of 63 patients re­ceived treat­ment.  Half of the patients re­ceived 10 mg/kg elotuzumab, and the other half re­ceived 20 mg/kg.

In the low-dose elotuzumab group, 90 per­cent of par­tic­i­pants achieved at least a partial re­sponse.  In the high-dose group, 72 per­cent achieved the same re­sponse, in­di­cating more fa­vor­able re­­sults with the lower dose.  Median time to re­sponse was 2 months.

The median pro­gres­sion-free sur­vival was not yet reached during the 4.9 months of follow-up.  However, pro­gres­sion-free sur­vival was more than 1 year in the Phase 1 trial.

Side effects were man­ageable in the majority of patients and were predominantly side effects seen with Revlimid and dexa­meth­a­sone.  The most common elotuzumab-related side effect was fever.  Preventative treat­ment helped to reduce, but not elim­i­nate, the oc­cur­rence of in­jec­tion site reac­tions.  No treat­ment-related deaths oc­curred.

The re­searchers will be going for­ward with the lower dose of elotuzumab in a Phase 3 trial that will start in early 2011.

Next, Dr. Suzanne Lentzsh pre­sented re­­sults of a Phase 1 study of Treanda ^[7] (bendamustine) in com­bi­na­tion with Revlimid and dexa­meth­a­sone in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma (abstract ^[8]).  Treanda is an al­kyl­at­ing agent approved to treat two types of leukemias.  The goal of this study was to de­ter­mine the max­i­mum tol­er­ated doses of Treanda and Revlimid in this com­bi­na­tion.

Treanda was tested at 75 and 100 mg/m² on days 1 and 2 of a 28 day cycle, and Revlimid was tested at 5 and 10 mg on days 1 to 21.  The doses tested for Revlimid are much lower than what is commonly used for induction treat­ment in myeloma, causing sev­er­al questions from the audience about the dosing choices used in the study.

The max­i­mum tol­er­ated dose was 75 mg/m² Treanda and 10 mg Revlimid plus dexa­meth­a­sone.

Low blood cell counts were common with this regi­men.  Almost half of the par­tic­i­pants ex­peri­enced severe low white blood cell counts.  Fatigue was the most common side effect that was not blood-related.

Among the 26 study par­tic­i­pants, 9 per­cent achieved a very good partial re­sponse, 57 per­cent a partial re­sponse, and 9 per­cent a minimal re­sponse.  Half of the patients achieved their best re­sponse within 1.8 months.

Median time to pro­gres­sion was 4.3 months, and median over­all sur­vival was 10.9 months.

Dr. Lentzsh said that this com­bi­na­tion may be par­tic­u­larly well suited for older patients or those with periph­eral neu­rop­athy.

The final myeloma-related pre­sen­ta­tion of the conference was given by Dr. Irene Ghobrial, who pre­sented re­­sults from a Phase 1/2 study of Torisel ^[9] (temsirolimus) in com­bi­na­tion with weekly Velcade ^[10] (bor­tez­o­mib) (abstract ^[11]).

Torisel is approved for the treat­ment of ad­vanced kidney cancer. A pre­vi­ous study showed that the over­all re­sponse rate with Torisel alone is 43 per­cent in myeloma patients.

This study in­cluded heavily pre-treated patients, most of whom had re­lapsed or were resistant to Velcade treat­ment. Phase 1 of the study in­cluded 20 patients, and Phase 2 in­cluded 43 patients.

The pur­pose of Phase 1 was to test the safety of the com­bi­na­tion to de­ter­mine the max­i­mum tol­er­ated doses of both drugs.  Velcade was tested at 1.3 and 1.6 mg/m², and Torisel was tested at 15 and 25 mg. The max­i­mum tol­er­ated doses were 1.6 mg/m² Velcade 4 out of 5 weeks and 25 mg Torisel weekly.

Almost all patients ex­peri­enced side effects, especially low platelet counts, which are asso­ci­ated with both Velcade and Torisel. Other types of low blood cell counts were common as well. One patient died due to septic shock.

In the Phase 2 study, 47 per­cent of patients responded to treat­ment with 5 per­cent com­plete re­sponses, 9 per­cent very good partial re­sponses, 19 per­cent partial re­sponses, and 14 per­cent minimal re­sponses. For patients pre­vi­ously treated with Velcade, re­sponses were predominantly stable dis­ease, with 20 per­cent achieving a minimal re­sponse or better.

Progression-free sur­vival was 5.6 months, and over­all sur­vival was 18.8 months.

Dr. Ghobrial said the trial re­­sults were promising in heavily pre­treated myeloma patients and that the com­bi­na­tion of Torisel and Velcade warrants fur­ther evaluation.

Earlier this week, The Myeloma Beacon pub­lished “as it hap­pens” up­dates from the fourth day of ASH in this thread ^[12] in the Beacon’s myeloma forums ^[13].