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ASCO 2012 Multiple Myeloma Update – Day Three: New Myeloma Treatments

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Published: Jun 3, 2012 8:26 pm

Today was the third day of the American Society of Clinical Oncology (ASCO) annual meeting, and the morning was filled with oral presentations about important myeloma-related studies.  Most of the talks were about potential new anti-myeloma drugs.

This update summarizes the presentations about panobinostat (Farydak), obatoclax, Treanda (bendamustine), and MLN9708 (ixazomib), which are all being developed as potential multiple myeloma treat­ments.  In addi­tion, the update includes a recap of a presenta­tion about the safety of long-term bis­phos­pho­nate use.

An update from earlier today summarized today’s presentations about carfilzomib (Kyprolis) and pomalidomide, both of which have been submitted to the U.S. Food and Drug Administration for potential approval as new myeloma treat­ments.

Panobinostat

One of the morning presentations was given by Dr. Melissa Alsina from the H. Lee Moffitt Cancer Center in Tampa, Florida.  Dr. Alsina presented a Phase 2 study of panobinostat in com­bi­na­tion with Velcade (bor­tez­o­mib) and dexamethasone (Decadron).

The study included 55 patients with re­lapsed and Velcade-refractory (resistant) multiple myeloma, with a median of four pre­vi­ous lines of ther­apy.  Almost all of the patients also had been treated with Revlimid (lena­lido­mide) in the past.

Overall, 31 per­cent of the patients responded to the panobinostat com­bi­na­tion, with 2 per­cent achieving a near complete response and 29 per­cent a partial response.

The most common severe side effects were low platelet counts, fatigue, low red blood cell counts, pneu­monia, low white blood cell counts, and diarrhea.  Peripheral neu­rop­athy -- which is pain, tingling, or loss of feeling in the extremities -- was experienced by 31 per­cent of the patients, but almost all cases were mild or mod­er­ate.

The panobinostat trial results were reviewed by Dr. Asher Chanan-Khan of the Mayo Clinic in Jacksonville, Florida, in a presentation that also took place during this morning's session.

Dr. Chanan-Khan described the results as interesting.  However, he does not feel he can yet draw any conclusions about panobinostat's role as a myeloma treat­ment based on these, or pre­vi­ous, trial results for the drug.

For further details, see the slide deck (PDF) for Dr. Chanan-Khan’s presentation, which he has made available as a courtesy to The Beacon’s readers.

Obatoclax

Dr. A. K. Stewart from the Mayo Clinic in Arizona then presented results from a Phase 1 study of obatoclax in com­bi­na­tion with Velcade for the treat­ment of re­lapsed multiple myeloma (abstract).

The study included 11 patients, 10 of whom were evaluated for response.  To take part in the trial, patients had to have had at least one pre­vi­ous line of ther­apy.  However, patients in the trial typically had relatively advanced myeloma, with the median time since first diag­nosis being 4.7 years.

Among the 10 patients who could be evaluated for a response, 40 per­cent achieved a partial response and 10 per­cent achieved a minimal response.

The side effect profile of the com­bi­na­tion, however, was quite negative.  In addi­tion to blood-related side effects often seen with myeloma treat­ments, the com­bi­na­tion also brought about unusual, and severe, neurologic side effects, such as extreme sleepiness or euphoria.

For this reason, Dr. Stewart said that he and his colleagues have no plans to conduct further studies of obatoclax as a potential myeloma treat­ment.

For further details, see the slide deck (PDF) for Dr. Stewart's presentation, which he has made available as a courtesy to The Beacon's readers.

Treanda

Next, Dr. Philippe Rodon from General Hospital in Blois, France, presented results from a Phase 2 study of Treanda in com­bi­na­tion with Velcade and dexa­meth­a­sone in elderly myeloma patients (abstract).

The study included 73 patients over 65 years of age who had re­lapsed or were refractory to treat­ment after one pre­vi­ous line of ther­apy.  Patients could not take part in the study, however, if they had been pre­vi­ously treated with Velcade or received a stem cell trans­plant.

Overall, 58 per­cent of patients responded, with 11 per­cent achieving a complete response, 12 per­cent a very good partial response, and 34 per­cent a partial response.

The most common severe side effects were low white blood cell counts, low platelet counts, sepsis, and gastro­in­tes­ti­nal upset.  Four patients died during the trial due to sepsis, and one patient died as  a result of kidney failure.

The results of the Treanda trial also were discussed by Dr. Chanan-Khan during his review presentation at this morning's session.  Dr. Chanan-Khan said that, in his opinion, the Treanda com­bi­na­tion showed significant toxicity, yet the efficacy of the com­bi­na­tion was not much better than Velcade alone com­bined with dexa­meth­a­sone.  Therefore, he would not be inclined to use the Treanda com­bi­na­tion in patients after just a single pre­vi­ous line of ther­apy.

As a courtesy to The Beacon's readers, Dr. Rodon has made his presentation available for download and viewing.

MLN9708

Later during the morning session, Dr. Sagar Lonial from the Emory Winship Cancer Institute presented results from a Phase 1 study of MLN9708 as a single-agent treat­ment (abstract).

This study included 58 patients with re­lapsed and refractory multiple myeloma.  The patients had a median of four pre­vi­ous lines of ther­apy, and the majority of trial participants had pre­vi­ously been treated with Velcade and either Revlimid or thalidomide (Thalomid).

As compared to the study presented during Saturday’s poster session in which MLN9708 was admin­istered once a week  (see related Beacon news), this study tested MLN9708 admin­istered twice a week.

Among the 53 patients evaluated for response, 11 per­cent responded to MLN9708 ther­apy.  Specifically, 2 per­cent achieved a stringent complete response, 4 per­cent achieved a very good partial response, and 6 per­cent achieved a partial response.

The most commonly observed serious side effects were low platelet counts, low white blood cell counts, fatigue, and rash.  Additionally, 11 per­cent had mild or mod­er­ate periph­eral neu­rop­athy.

Bisphosphonates

One of the last presentations during this morning's session was given by Dr. Gareth Morgan from the National Cancer Research Institute in London.  Dr. Morgan presented long-term efficacy and safety data for bis­phos­pho­nate ther­apy (abstract), based on updated results from the well-known "MRC Myeloma IX" clinical trial.

The results are based on data from 1,960 myeloma patients who received anti-myeloma ther­apy along with either Zometa (zoledronic acid) or Bonefos (clodronate).  Both of these drugs belong to the class of bone-building treat­ments known as bis­phos­pho­nates.  However, Bonefos is not sold in the United States.

At a median follow-up of 5.8 years, patients who received Zometa had improved pro­gres­sion-free and over­all survival relative to those who received Bonefos.

Dr. Morgan stated that long-term bis­phos­pho­nate ther­apy was generally well tolerated.  However, patients receiving Zometa were at higher risk of developing osteo­necrosis of the jaw (ONJ), a con­di­tion that is asso­ci­ated with a loss of blood supply to the jaw, causing the jawbone tissue to die.

Among the patients treated with Zometa, 3.7 per­cent developed ONJ, compared to 0.5 per­cent of the patients treated with Bonefos.

Dr. Morgan and his colleagues found that patients typically developed ONJ between 8 and 30 months of bis­phos­pho­nate ther­apy, with the risk ceasing around 3 years.  They also found that patients treated with thalido­mide had a lower risk of developing ONJ.

Myeloma-related presentations from Day 4 of the 2012 ASCO annual meeting also will be summarized in daily updates to be published tomorrow.  Additional 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 coverage.

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  • Myeloma Beacon Staff said:

    Dr. Rodon has kindly agreed to make available to The Beacon's readers his presentation on the Velcade-Treanda-Dexamethasone combination for relapsed / refractory myeloma patients. It can be viewed by clicking this link: http://bit.ly/L880oX .