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ASCO 2012 Multiple Myeloma Update – Day Four: Poster Presentations On New Myeloma Treatments

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Published: Jun 4, 2012 8:23 pm; Updated: Jun 6, 2012 11:00 am

This year’s American Society of Clinical Oncology (ASCO) annual meeting, which is being held in Chicago, began on Friday and goes through tomorrow. How­ever, to­day is the last day with any myeloma-related sessions.

Several myeloma-related oral pre­sen­ta­tions were given this morn­ing and were summarized in an up­date pub­lished earlier to­day (see re­lated Beacon news).

This afternoon featured a poster session in which im­por­tant new re­search findings were summarized on posters throughout a large conference hall.

The stud­ies pre­sented this afternoon were on a wide variety of myeloma-related topics ranging from new treat­ments being devel­oped for myeloma, to cur­rently used regi­mens, to sec­ond­ary cancers, to precursor myeloma dis­eases, and much more.

This up­date covers some of the myeloma-related stud­ies pre­sented during the poster session. In par­tic­u­lar, this article covers posters about new treat­ments that are being devel­oped for myeloma.  Some of the posters in­cluded pre­lim­i­nary re­­sults from on­go­ing clin­i­cal trials.  Others described the design of on­go­ing clin­i­cal trials for which re­­sults are not yet avail­able.

Additional up­dates will summarize posters from this afternoon that were about other myeloma-related topics.

Carfilzomib

The session in­cluded posters about three dif­fer­en­t carfilzomib (Kyprolis) stud­ies, one of which -- described a bit fur­ther below -- studied the com­bi­na­tion of car­filz­o­mib and panobinostat (Farydak).

Carfilzomib is being devel­oped by Onyx Pharma­ceu­ticals (NASDAQ: ONXX). It works similarly to Velcade (bor­tez­o­mib) and is cur­rently being reviewed by the U.S. Food and Drug Admin­istra­tion for po­ten­tial ap­prov­al as a new myeloma treat­ment.

One poster highlighted re­­sults from a Phase 1/2 study of the safety and ef­fi­cacy of car­filz­o­mib as a replacement ther­apy for Velcade in patients who progressed while taking Velcade-containing regi­mens (abstract). Early re­­sults of the study sug­gest that car­filz­o­mib is an ef­fec­tive and tol­er­able re­place­ment for Velcade in these patients.

The study in­cluded 27 patients who had re­ceived a median of six pre­vi­ous lines of ther­apy.  Of the 27 patients, 22 of whom were eval­u­ated for re­sponse. The over­all re­sponse rate was 51 per­cent, with 23 per­cent of patients achieving a com­plete re­sponse, 5 per­cent a very good partial re­sponse, and 23 per­cent a partial re­sponse.

The median pro­gres­sion-free sur­vival time was 9.8 months.

The most common severe side effects were low platelet and lym­pho­cyte counts as well as fever, pneu­monia, and sepsis.

Another car­filz­o­mib poster summarized re­­sults of an analysis of the safety of car­filz­o­mib in re­lapsed and re­frac­tory myeloma patients. In the analysis, re­searchers assessed the rate of var­i­ous blood-related side effects in 526 myeloma patients treated with single-agent car­filz­o­mib across four dif­fer­en­t Phase 2 stud­ies (abstract).

According to the study in­ves­ti­ga­tors, 70 per­cent of patients treated with car­filz­o­mib ex­peri­enced blood-related side effects.  However, severe to life-threatening blood-related side effects were both infrequent and lasted for short periods of time. These in­cluded low platelet, lym­pho­cyte, neu­tro­phil, and red blood cell counts.

Based on their re­­sults, the re­searchers concluded that the safety profile of car­filz­o­mib was similar to or better than that of cur­rently approved myeloma ther­a­pies.

Carfilzomib Plus Panobinostat

The final car­filz­o­mib-related poster described an on­go­ing Phase 1/2 clin­i­cal trial eval­u­ating the safety and ef­fi­cacy of the com­bi­na­tion of car­filz­o­mib plus panobinostat for the treat­ment of re­lapsed and re­frac­tory mul­ti­ple myeloma (abstract).  Results are not yet avail­able for this trial.

Panobinostat is an oral drug that is being devel­oped by the pharma­ceutical com­pany Novartis (NYSE: NVS) for a variety of dif­fer­en­t cancers. It belongs to a class of drugs called histone deacetylase (HDAC) in­hib­i­tors, which work by in­creas­ing the pro­duc­tion of pro­teins that slow cell division and cause cell death.

The study plans to en­roll up to 52 re­lapsed or re­frac­tory myeloma patients.

The Phase 1 portion of the study will in­clude approx­i­mately 24 patients and will de­ter­mine the max­i­mum tol­er­ated doses of car­filz­o­mib and panobinostat when admin­istered to­geth­er.

In the Phase 2 portion of the study, approx­i­mately 25 patients will re­ceive treat­ment with the optimal doses of the car­filz­o­mib-panobinostat com­bi­na­tion. Re­searchers will then eval­u­ate the over­all re­sponse rate, time to pro­gres­sion, pro­gres­sion-free sur­vival, and over­all sur­vival of patients treated with this regi­men as well as the safety of the regi­men.

Elotuzumab

The session also in­cluded four dif­fer­en­t posters about elotuzumab stud­ies.

Elotuzumab is a mono­clonal anti­body being devel­oped by Bristol-Myers Squibb (NYSE: BMY).  It works by identifying pro­teins on the surface of myeloma cells and signalling for the im­mune sys­tem to destroy the cancer cells.

Three posters described the designs of on­go­ing clin­i­cal trials investigating elotuzumab-containing regi­mens. Results are not yet avail­able for these trials.

Two of the stud­ies are Phase 3 clin­i­cal trials investigating the com­bi­na­tion of elotuzumab, Revlimid (lena­lido­mide), and dexamethasone (Decadron) com­pared to Revlimid plus dexa­meth­a­sone alone.

One of these trials plans to test the com­bi­na­tion in 750 newly diag­nosed myeloma patients who are in­eli­gible for stem cell trans­plan­ta­tion (abstract).  The other plans to test the com­bi­na­tion in 640 re­lapsed and re­frac­tory myeloma patients (abstract).

Another on­go­ing study is a Phase 2 clin­i­cal trial investigating the com­bi­na­tion of elotuzumab, Velcade, and dexa­meth­a­sone com­pared to Velcade plus dexa­meth­a­sone alone (abstract).  The trial plans to test the com­bi­na­tion in 150 re­lapsed and re­frac­tory myeloma patients.

In each of these trials, patients will be eval­u­ated for re­sponse.  Progression-free sur­vival and over­all sur­vival will also be tracked.

Another poster pre­sented a laboratory study in which re­searchers in­ves­ti­gated whether the com­bi­na­tion of elotuzumab plus Revlimid dem­onstrates greater anti-myeloma ac­­tiv­ity com­pared to elotuzumab or Revlimid alone (abstract).

The re­searchers found that when myeloma cells and blood cells were incubated with elotuzumab or Revlimid alone, some of the myeloma cells died.  However, sig­nif­i­cantly more myeloma cells were killed when treated with the com­bi­na­tion of elotuzumab and Revlimid.  The re­searchers also showed that elotuzumab activated cer­tain im­mune cells known as natural killer cells, which kill myeloma cells.

SNS01-T

Another poster from the session described the design of an on­go­ing Phase 1/2 trial investigating the safety and tol­er­a­bil­ity of SNS01-T in re­lapsed and re­frac­tory mul­ti­ple myeloma patients (abstract).  Results are not yet avail­able for this trial (see up­date below).

SNS01-T is being devel­oped by the pharma­ceu­tical com­pany Senesco (NYSEAMEX: SNT). It sel­ectively causes cells to die by targeting a pro­tein called eIF5A, which is be­lieved to be an im­por­tant regulator of cell growth and cell death.

The trial plans to en­roll 15 patients who are not eli­gible for any standard treat­ment op­tions.  They will be divided into sev­er­al groups, each of which will re­ceive a higher dose of SNS01-T.

Participants will be eval­u­ated for re­sponse, and pro­gres­sion-free and over­all sur­vival will also be tracked.

Update (June 6, 2012; 11:00 am) - In a press re­lease issued on Monday, Senesco re­leased initial re­­sults from the trial that were not in­cluded in the poster pre­sented at ASCO.   The com­pany reported that five patients have been en­rolled in the study so far.  Additionally one has com­pleted treat­ment and has achieved stable dis­ease.  However, two patients dis­con­tinued ther­apy due to dis­ease pro­gres­sion. No dose-limiting side effects have been reported.

Myeloma Vaccine

The search for vaccines to treat mul­ti­ple myeloma and other cancers has been under way for sev­er­al years.  Another poster from this afternoon’s session described the design of an on­go­ing Phase 1 clin­i­cal trial investigating a vaccine for the treat­ment of myeloma patients undergoing stem cell trans­plan­ta­tion (abstract). Results are not yet avail­able for this trial.

The vaccine, which is being devel­oped by GlaxoSmithKline (NYSE: GSK), targets the pro­tein MAGE-A3, which is present on the surface of myeloma and other cancer cells, but not nor­mal cells.  The vaccine trains im­mune cells to attack cells with MAGE-A3 on their surface.  The vaccine is in Phase 3 trials for lung cancer and mel­anoma.  However, this is the first time the vaccine is being tested for myeloma or in patients undergoing stem cell trans­plan­ta­tion.

The trial plans to en­roll 16 patients who have been diag­nosed with mul­ti­ple myeloma within the last year and achieved at least a very good partial re­sponse to their induction ther­apy.

Patients will be vaccinated six weeks before their stem cell trans­plant.  Three weeks after vaccination, lym­pho­cytes (a type of im­mune cell that have hopefully been trained by the vaccine to attack myeloma cells) will be collected.  These will be re-infused three days after stem cell trans­plan­ta­tion.  Patients will be vaccinated seven more times within the nine months fol­low­ing their trans­plant.

Additional myeloma-related posters from to­day, Day 4 of the ASCO 2012 meeting, also will be summarized in ASCO 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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7 Comments »

  • nancy shamanna said:

    Thanks for the great article , Julie. On the topic of the MAGE-A3 vaccine test, I see that the vaccination, six weeks before transplant, but after induction chemo I assume, would save the lymphocytes for re-infusion after the melphalan had destroyed the patient's bone marrow (SCT). Did they say in the full paper whether the leukaphoresis (collection of the lymphocytes) would occur before the aphoresis collection of the patient's own stem cells (assuming this is an auto type collection)? I ask this because strong chemo is also used before stem cell collection, and it possibly could damage the lymphocytes.

  • Julie Shilane (author) said:

    Hi Nancy,

    Thanks for the follow-up questions. As you suspected, participants will receive induction therapy followed by vaccination, lymphocyte collection, then stem cell collection, high-dose chemotherapy with melphalan, and finally stem cell transplantation and re-infusion of the lymphocytes.

  • Dan in Phoenix said:

    Hi Julie,

    Did the authors mention the possibility of purging the lymphocytes of CD20+ B cells which are potentially MM Stem cells (according to Bill Matsui-Hopkins model) and not desirabable to be reinfused after transplant? Most of the benefit of the vaccine would probably come from the killer T cells anyway.

    If we are going to make real progress and cure myeloma we need to consider all the science for the benefit of the patients!

  • Julie Shilane (author) said:

    Hi Dan,

    The authors do not mention purging the lymphocytes, or the stem cells for that matter.

    Dr. Adam Cohen, one of the Beacon's Medical Advisors, is the first author on the poster, so I will follow up with him to see if he can provide any further detail on the methods he and his colleagues will be using.

  • Dan in Phoenix said:

    I appreciate this and the fine work of the Beacon Team Julie. Thanks

  • Adam Cohen said:

    Hi all,
    We are not doing any purging of the peripheral blood lymphocytes or stem cells in this study. Several studies in the 90's examined purging stem cell products of myeloma cells, without clinical benefit seen. The Hopkins group (and others) have tried to eliminate the putative CD20+ myeloma stem cell (which still remains a controversial concept) using rituximab post-SCT, again without clinical benefit seen. While our primary goal with the vaccination and initial leukopheresis is to activate and transfer "killer T cells", as you suggest, there are many vaccines where the primary protective effect is mediated by antibodies, which requires activation and expansion of CD20+ B cells. So there may be a real downside with regard to immunity by taking these cells out. Since we don't know yet which immune cells will be most important for response to the vaccine and for controlling the myeloma, we've opted not to manipulate the cell products in this study.
    Hope this is helpful.
    Best regards,
    Adam Cohen

  • Dan in Phoenix said:

    Thanks for the feedback Adam.
    It seems you are involved in this exciting project. I didn't mean to criticize, just suggesting next steps to improve upon it. I am unique as a 25 year survivor with systemic AL-amyloidosis diagnosed in 1987 with 25 year remission without ASCT just interferon maintanance after two "experimental" therapies for those day (VAD then the Sloan Kettering M2 protocol- I think).
    Diagnosed and followed Barlogie from MD Anderson to UAMS now getting treatment in collaboration with Stewart (Mayo-AZ) and Barlogie- a testament to pick the brightest minds your can find for your care. A concept I urge for all MM patients.
    I am also a PhD tumor immunologist and cancer cell biologist with an interest in cancer stem cells. It doesn't surprise me that killing cancer stem cells takes more than rituximab because there are more survival signals than death signals both in the MM stem cells and the supportive "niche cells" that keep the cancer alive for future relapse.
    All of the excellent discoveries made with the MM drugs are fantastic and definately leading to longer survival but once the patient is in remission (by whatever method we use) we need to go after the true source of the disease. I tell my students it's like trying to put out a fire, if you beat down the flames (MM plasma cells) without destroying the embers (MM Stem cells) it is only a matter of time before the fire returns.
    I'd love to see an collaborative initiative in myeloma community (scientists, clinicians and even Pharma) perhaps under MMRF to develop anti-MM stem cell-targeted therapy.
    It could be our best hope for a real cure and as I alluded to earlier the basic science science is beginning to be developed.