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ASH 2010 Multiple Myeloma Update – Day Four

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Published: Dec 9, 2010 3:15 pm

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 in myeloma patients who had re­lapsed mul­ti­ple times and did not respond to their last treat­ment (abstract).

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, a humanized mono­clonal anti­body (abstract).  Elotuzumab was given in com­bi­na­tion with Revlimid (lena­lido­mide) and low-dose dexamethasone (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 (bendamustine) in com­bi­na­tion with Revlimid and dexa­meth­a­sone in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma (abstract).  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 (temsirolimus) in com­bi­na­tion with weekly Velcade (bor­tez­o­mib) (abstract).

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 in the Beacon’s myeloma forums.

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4 Comments »

  • Sean Murray said:

    Julie

    Thank you, and all at the MB, for four days of excellent reporting from the ASH conference in Orlando. I join all MM patients in following the exciting news as it further unfolds in the Beacon.

    Sean M.

  • John Williamson said:

    Excellent coverage of the ASH conference Julie. The use of layman language combined with disclosure of the major statistics provided an understandable format for the MM patients. Thanks for the clear communications geared to the technical level of your audience.

  • Julie Shilane (author) said:

    Thanks, Sean and John! All of us here at The Myeloma Beacon are glad to hear that you found our coverage helpful and easy to understand.

  • Peter Parker said:

    Julie, thank you from our group also.
    Great job!!!! Peter