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New Orleans, LA December 10, 2013 - As I'm sitting here in the New Orleans airport, flight delays have given me a chance to summarize my thoughts following all the meetings at the 2013 American Society of Hematology annual conference. Here are highlights for me and all multiple myeloma (MM) patients, in no particular order:

    • Monoclonal Antibodies  This seems to be the next area beyond proteasome inhibitors (e.g. Velcade) and IMiDs (e.g. Revlimid) that will yield drugs for the field of targeted therapies.  Daratumumab, Elotuzumab, and SAR-650984 are already in trials, but I saw others which have showed success in the labs and mouse models that are heading to Phase I clinical trials.
    • Fit/Unfit/Frail  A way of categorizing patients using geriatric studies that will help determine a best treatment for older patients while focusing on quality of life.
    • Smoldering Multiple Myeloma  There's a belief that, like other cancers, earlier treatment means longer term success. While the standard treatment for SMM is watch-and-wait, there's a portion of SMM patients that are high risk and will likely progress to full-blown MM within a couple of years. Perhaps treatment for high risk SMM patients can significantly delay the onset of MM, thus preventing earlier organ damage.
    • Cytoxan Instead of Melphalan  Since Cytoxan is less likely to damage bone marrow and blood counts, several presenters recommended using Cytoxan as the alkylating agent in treatment rather than melphalan.
    • So Many Options The list of treatment options since last year's ASH continues to grow now that we have carfilzomib and pomalidomide. And there seem so be clinical trials for every diagnosis phase...smoldering through high-risk MM, newly diagnosed through relapsed/refractory. Trials are so important because that's how we move possible treatment forward, so perhaps you want to ask your MM doctor if there's a trial that's beneficial for you.
    • Maintenance  This is still a hot topic. Most agree that maintenance (a better name might be "continued treatment") improves progression-free survival.  But does it extend overall survival? I heard one doctor say it best--"Maintenance certainly helps some...we just don't know which ones."  I guess you could say the same for any treatment (e.g. transplant). More maintenance studies are necessary before there's full agreement on the benefit.

That's it. Next year's ASH meeting is in San Francisco. Together we can help each other.

 -- Jack Aiello

New Orleans, LA December 9, 2013--As I mentioned previously, today is Myeloma Monday, meaning the first oral presentation began at 7 a.m. and the last one ended at 6 p.m.  Yes, we had some breaks, but I used them to review the new posters (none will be mentioned here) and walk to different rooms in the large Convention Center. Each oral presentation is about 13 minutes with 2 minutes of questions and answers. The 15-minute time limit is monitored very closely.

Here's a sample title of the first presentation I attended (remember, it's 7 a.m.): "Novel AKT Inhibitor Afuresertib in Combination With Bortezomib and Dexamethasone Demonstrates Favorable Safety Profile and Significant Activity in Patients with Relapsed/Refractory Multiple Myeloma." The Power Point presentation topics typically cover Background, Trial Rationale, Treatment Plan, Patient Demographics, Trial Results (Responses, Survival Outcomes, Adverse Side Effects), Conclusion, and Future Directions. 

I'm watching densely written slides fly by at real time speed, all the while trying to record accurate information and listen to what's being said.  It's pretty intense as you listen to the terminology (for example, we know bortezomib as Velcade) and try to interpret the results.

In these trials, I look for Clinical Trial Phase (the one above was at Phase I), "n" representing number of patients, Responses (e.g. Complete Response, Overall Response), Survivals (e.g. Progression Free Survival, Overall Survival), Adverse Events/toxicity (both hematologic-blood and non-hematologic) and Conclusion/Summary. Phase I trials consists of a handful of patients to determine Maximum Tolerated Dose (MTD); Phase II, with roughly 50-100 patients, examines treatment efficacy; and Phase III, with several hundred patients, compares that new treatment/drug with a current standard of care. Finally, I look at who the trial is intended for such as newly diagnosed patients or relapsed/refractory myeloma (RRMM) patients.

Just a few of these talks are mentioned below all for RRMM patients unless otherwise noted:

Drugs I heard about today in Phase I trials include:

  • SAR650984...CD38 monoclonal antibody that has single agent activity.

This adds to other monoclonal antibodies Elotuzumab and Daratumumab, definitely a hot area for MM research.

Phase II trials I found interesting include:

  • ARRY-520 (KSP Inhibitor) which had single agent activity combined with Vel-Rev or just Dex.  Most interesting was the detection of a biomarker called AAG that can help determine if a patient will respond to ARRY-520.
  • Vel-Mel-Pred 9 cycles followed by Rev-dex 9 cycles versus alternating each cycle for newly diagnosed elderly patients.  Results didn't seem to matter overall but it might for a given individual. 
  • Oral MLN9708 (Ixazomib) + Rev + Dex is an effective all-oral regimen containing a proteasome inhibitor and IMID for newly diagnosed patients.
  • Carfilzomib + Rev + Dex followed by Rev maintenance in newly diagnosed patients.
  • Carfilzomib + Cytoxan + Dex for newly diagnosed patients
  • Pomalidomide + Dex for high-risk del 17p or t(4:14) patients

Phase III trials of interest were:

  • Velcade Induction followed by transplant followed by Velcade maintenance 
  • The measurement of PFS2 was defined as Progress Free Survival through relapse and another treatment therapy.  PFS2 was proposed to show in a large French Phase III study that Revlimid maintenance didn't result in Overall Survival improvement over no maintenance.  However, this was argued by other myeloma experts. Maintenance still needs more study.

That's enough for now.  There are so many others I attended and even more I couldn't attend since there were 835 Myeloma abstracts at this year's ASH.

While typing this, I'm watching a wonderful IMWG Conference Series live webcast, "Making Sense of Treatment," featuring myeloma experts Drs. Brian Durie, Antonio Palumbo, Joseph Mikhael, and Ola Landgren.  Among these four experts, there's both agreement and disagreement.  We all want the "best" treatment and get frustrated not having definitive answers.  

Well, let me tell you what's worse--having only two treatment options: Melphalan-Prednisone or VAD induction + SCT, and told the average life-span is only 2-3 years. That was my choice when I was diagnosed 19 years ago.  Personally, I'm much happier having more and much more effective/less toxic options.

ASH ends tomorrow morning so my final blog report will probably be written from the airport or after I return home.  I'm looking forward to both.

Stay educated.

-- Jack Aiello
New Orleans, LA December 8, 2013--Today was a busy one, having just returned from a meeting that ended at 10 p.m., but more about that later.  I'm sure a highlight for any presenter at the annual meeting of the American Society of Hematology (ASH) is to be selected for a Plenary session. This is a 30-minute oral presentation with no other competing talks. As such, several thousand attendees are in the audience.

One of today's Plenary session talks was given by Dr. Thierry Facon from France about Phase III trial results for 1,623 (!) newly diagnosed myeloma patients, at least 65 years old, who were randomized into 3 study arms: (A) Revlimid plus dexamethasone until disease progression; (B) Revlimid plus dex for a fixed 18 cycles (72 weeks); and (C) Melphalan-Prednisone-Thalidomide for a fixed 12 cycles (72 weeks).

Results for Arms (A), (B), and (C) respectively showed:

  • Overall Response Rate (%): 75  73  62
  • Progression-Free Survival (mos):  26  21  21
  • Median 4-yr Overall Survival (%):  59  56  51

While some of the numbers may look close, there are important differences as you drill deeper.  For example, PFS curves for (A) and (B) were very close through 18 months, but then the curve separation became apparent and growing.  Another factor supporting (A) as the preferred treatment was that (A) had a 1-year improvement over the others in a measurement called Time-To-Progression. And while Arms (A) and (B) both had about 28% grade 3-4 neutropenia (low white count), Arm (C) had 45%.

I've highlighted a few posters [abstract number] below:

  • Poster [3178] compared outcomes for Velcade-Cytoxin-Dex (CyBorD) versus Velcade-Revlimid-Dex (VRD) for newly diagnosed patients. Besides comparable PFS (70% vs 68% at 2 yrs) and OS (92% vs 85% at 2yrs), cost was also examined.  The cost for 4 cycles CyBorD versus VRD was $37K vs $67K.  Both costs are outrageous but I'm glad to see studies looking at this.
  • Phase III study in Poster [3189] showed that Perifosine with Velcade plus Dex in patients previously treated with Velcade showed no benefit in PFS or ORR. It's also useful to eliminate some drug usage.
  • Poster [3209] examined responses to Revlimid in newly diagnosed patients with and without continuous therapy. It demonstrated that patients stopping Revlimid after 1 year and achieving a VGPR or better can result in long-term (4 yrs) disease control and can be considered a treatment strategy. 

My day ended with a very educational and inspirational workshop for International Journalists.  There were approximately 100 in attendance, many with headsets providing real-time translation, and also streamed live to 20 countries.  A summary of several ASH highlights was presented along with future goals of developing better treatments, perhaps at earlier diagnosis, and build upon the IMF's Black Swan Research Initiative to have better testing tools (Minimum Residual Disease) that more accurately determines patient responses. 

Well, that's about it for the day.  Lots of information, and yet tomorrow is also known as "Myeloma Monday" with oral presentation going from 7 a.m. to 8p.m.  And then I'll be watching the International Myeloma Working Group (IMWG) conference series tomorrow evening (check the IMF website myeloma.org for more details).

It's late and I have a 5:30 am wake-up call.  

-- Jack Aiello
New Orleans, LA December 7, 2013--Today was the official start of the annual meeting of the American Society of Hematology (ASH) with the Exhibit Hall open, posters displayed and education talks presented, which is what I'll start with. This session featured three renowned myeloma experts, each speaking for about 30 minutes: Dr. Ola Landgren (National Cancer Institute), Dr. Maria-Victoria Mateos (Spain) and Dr. Phillip McCarthy (Roswell Park Cancer Institute, Buffalo, NY). All three doctors summarized what is known at this instant in time, pending future announcements at ASH.

Dr. Landgren discussed MGUS and smoldering myeloma (SMM) in terms of biological insights and early treatment (contrary to the current watch and wait recommendation). I found it interesting that he mentioned one could think of myeloma as a metastatic disease that evolves from a Solitary Plasmacytoma (passing through the MGUS and SMM phases). While MGUS only has a .5-1%/yr progression to full-blown myeloma, SMM is much higher at 10%/yr during the first 5 years. All of this says that many of us had precursors to myeloma before we were diagnosed.  

So one might ask if earlier treatment would have delayed the onset of full-blown myeloma. This is a relatively new area of investigation with several clinical trials examining possible answers.  These trials are incorporating difference risk stratifications for SMM patients so that ultimately High or Ultra-High Risk SMM patients may benefit with early treatment whereas MGUS and standard-risk SMM patients may still fall into the watch and wait category. We'll see what happens as these trials progress.

Dr. Mateos focused on summarizing treatments available for non-transplant ("elderly") patients. She indicated the importance of evaluating such a patient as being Fit, Unfit, or Frail.  All the well-known treatments are available to "Fit" patients, while "Unfit" patients may benefit by lower dosages and "Frail" patients should avoid Melphalan.

I found several posters of interest.  (You can actually look up the abstract for these posters by going to www.hematology.org and looking up the poster number, which I'll identify within square brackets [ ]. The actually poster may contain updated information.)

• Poster [1888] suggested that if a solitary plasmacytoma has abnormal PET-CT scans and serum Free-Light-Chain values, perhaps myeloma treatment should start after appropriate surgery/radiation.

• Poster [1933] demonstrated that Carfilzomib plus Melphalan and Prednisone for newly diagnosed elderly patients is a promising therapy. In a Phase I/II trial, it showed an Overall Response Rate (ORR) of 91%, including 10% Complete Response (CR) and 45% Very Good Partial Response (VGPR).

• Poster [1940] looked at Pomalidomide plus Velcade plus Dex in patients with relapsed/refractory myeloma (RRMM). This PVD regimen showed ORR of 90% for patients refractory to Revlimid.

• Poster [1974] showed Bendamustine, Velcade and Dex (BVD) for RRMM patients an effective treatment with ORR-77% (CR 20%, VGPR 20%)

• Poster [1979] explained that treatment with Pomalidomide directly after being treatment with either Revlimid or Thalidomide actually has lower response rate and shorter treatment duration.

Tonight I attended International Myeloma Foundation (IMF) Grant Awards reception, where four myeloma patients shared their personal stories and the IMF awarded a number of $80K and $50K grants to researchers primed to make new discoveries benefitting patients in the future.

Definitely a nice way to end the day. 

-- Jack Aiello

Friday was the day before the official start of ASH, otherwise known as Symposium Day where organizations like the International Myeloma Foundation (IMF) provide a panel of myeloma (MM) experts to discuss various topics and are typically attended by hundreds of clinicians.

But first, I have two other topics of discussion. I attended a meeting of the IMF's Global Myeloma Alliance, where representatives of advocacy organizations around the world attended in person or by phone. Participating countries included Canada, Israel, UK, Spain, Australia, South Korea, Malaysia and more. The goal of the GMA is to build upon the knowledge that exists within different countries on topics such as drug access and funding, and leverage that expertise in countries that need it.

Also, I just saw a joint press release from the IMF and Onyx (carfilzomib/Kyprolis) announcing a partnership in support of the IMF's Black Swan Research Initiative®. The goal of BSRI®  is to develop better testing (MRD -- minimum residual disease) that can more quickly determine new drug efficacy and possible cures (MRD-Zero). 

Next I attended the IMF Symposium, which was moderated by IMF Chairman Dr. Brian Durie and featured myeloma experts Doctors Shaji Kumar and Vincent Rajkumar (Mayo Clinic); Philippe Moreau (France), Jesus San-Miguel (Spain) and Antonio Palumbo (Italy). The format of this meeting attended by nearly 1,000 clinicians from around the world was to look at 5 case studies. For each study, a treatment question was asked, 2 experts presented Pro (Yes) and Con (No) sides, there was discussion, and the audience voted before and after each case study.

Overall, this symposium validated the importance of having a myeloma expert on your side. Beware though, if you have two or more, they may disagree. 

What follows are the questions and my takeaways in some detail:

 I) Treat High Risk Smoldering Myeloma (HR-SMM)?

First we need to agree on the definition of HR-SMM.  M-spike > 5 g/l AND plasma % > 33% is a possibility but there are others. Dr. San-Miguel (Pro) noted that every other cancer, e.g. breast, lung, benefit from early treatment so why not SMM, where the standard of care is "watch and wait"? And a recent Spanish study for HR-SMM (different definition) using Revlimd + dexamethasone showed an improvement of progression free survival (PFS) by about 2 years. Dr. Rajkumar (Con) said HR-SMM is not defined well.  We should look at ultra-HR-SMM (with del 17p or t(4:14)) and treat as MM.  And for standard risk SMM, watch and wait.  Then for the other group of HR-SMM, look at an on-going trial such as E3A06 that compares arms Revlimid-only (no dex) usage versus watch and wait. The audience voted about 37% pro vs 63% con.

II) Early Stem Cell Transplant (SCT) -Yes or No?

Dr. Moreau argued the Yes side, noting various studies. One showed three-year overall survival of 94% (w SCT) versus 78% (w/o SCT). Dr. Kumar argued No, countering that while an SCT can clearly help some patients, we don't know who they are. An SCT should not be mandatory but could be done at relapse. Both agreed that future results from the on-going IFM-DFCI trial comparing early versus late SCT will be valuable. The audience voted about 82% yes and 18% no.

III) Should Melphalan (Mel) be considered for induction treatment?  

Dr. San-Miguel (Yes) showed that in a study of Mel-Pred-Rev versus Mel-Pred, the results were nearly the same. So Mel had a bigger influence on treatment response than Rev. While Dr. Palumbo (No) noted that complete response (CR) rates correlate to long-term outcomes and showed there are better alternatives than Mel combinations (e.g. Vel-Mel-Pred) for generating CR's (e.g. Cfz-Rev-dex).  The audience voted about 44% yes and 56% no.

IV) Maintenance Therapy...Yes or No?

The audience vote going into this presentation was 71% yes versus 29% no.  Dr. Palumbo (Yes) showed trial results for either Rev or Vel maintenance provided a 1-year improvement before the myeloma reappears. Maintenance has also resulted in fewer deaths compared to non-maintenance arms in trials. As he stated, "Maintenance is really continued treatment." And drug-resistant relapse is much less of an issue than clonal MM cells causing relapse. Dr. Rajkumar (No) countered with the fact that "maintenance after an SCT removes the allure of a treatment-free benefit." He also noted that PFS is not the right endpoint and OS benefits are inconsistent.  He recommend that high-risk MM pts (del 17 or t(4:14)) benefit from Velcade maintenance; however standard-risk patients who achieve less than a VGPR (Very Good Partial Response) from the SCT should get Rev maintenance for 2 years, while those getting a VGPR or better should not get any maintenance. His arguments changed the minds of the audience, which then voted 45% yes and 55% no.

V) Should new therapies such as carfilzomib (Cfz) or pomolidomide (Pom) be used in the salvage setting - Yes or No?

Before the presentation, the audience voted 60% yes and 40% no. Dr. Kumar (Yes) showed that both Cfz and Pom have had good Overall Response Rates (ORR) in patients refractory to both Rev and Vel.  Dr Moreau (No) argued that since the case study had relapsed after 3 years on Rev maintenance after an SCT, that both non-Rev trials as well as a second SCT were viable treatment options. He convinced the audience which changed their vote to 41% yes and 59% no.

That's it. Great session, demonstrating the complexities of myeloma (there really are "multiple" myelomas) and treatment options.  

-- Jack Aiello

I'm off to New Orleans, site of this year's American Society of Hematology (ASH) conference.  Through the IMF, I'll be blogging each night about the highlights that occurred earlier that day. 

As background, I attended my first ASH meeting seven years ago and found it a bit like being diagnosed with myeloma nearly 19 years ago. The terminology and amount of information was overwhelming, understandably though since the intended audience is the 20,000 researchers and oncologists, presenting and learning the latest updates for blood cancers, including myeloma (MM). I loved learning whatever I could understand because I was energized by all the great research being done. I learned so much at that first meeting and haven't missed an ASH conference since. 

I also learned to prepare a few weeks ahead of time, creating my personal agenda of talks I want to attend. These presentations will typically be on clinical trial results rather than on biological lab studies because these are more immediate value to patients currently in treatment or soon to be diagnosed.

Officially, the ASH meeting runs from Saturday, Dec. 7 through Tuesday, Dec. 10.  Each day consists of:

Exhibit Hall: Analogous to a trade show in Silicon Valley (my home) where pharmaceutical companies (nearly 300), medical suppliers, research and diagnostic companies, non-profits, and publications involved with blood cancers have a booth and provide product information. IMF has a booth where they interview MM experts for subsequent posting on their website.

Posters Hall:  Each day, over 1,000 new 5x3-foot posters are hung displaying research projects from selected abstracts with details of background, method, patient demographics (could be Mouse Models), results for both responses and adverse side effects, and conclusions. 

Oral Presentations: Nearly 1,000 abstracts are designated for oral presentations, typically 10 minutes of slides and 5 minutes for Q&As. Unfortunately, there are simultaneous presentations, so no one can attend everything, even for just a single disease like MM...thus the reason for working out my agenda before arriving at ASH.

Today (Friday, Dec. 6), the day before the official start of ASH, is designated as Symposium Day, with Symposium sessions scheduled for 3 to 4 hours in the morning, afternoon and evening. For example, the IMF symposium is tomorrow afternoon with a panel of Myeloma experts discussing various MM issues. While answers in these sessions cannot include information yet-to-be-released at ASH, it's always fascinating to see how MM experts have different opinions/recommendations to handle various patient case studies or posed questions for which there's no definite answer yet...welcome to the world of myeloma. I'm sure some of those differences will also be heard at the IMF Monday night debate, which can be heard live here.

Friday morning I'll be attending a meeting of the IMF's Global Myeloma Alliance.  Our first meeting was this past summer and the goal of these 20+ advocates is to address several of the international MM issues, such as the unavailability of certain treatments due to government regulations. 

I'm with several other patients the IMF brought to ASH. We'll be blogging, posting on Facebook, and Twitter, and we hope to keep you well informed from our individual patient perspectives.  Of course, you'll have other vehicles to learn about ASH in the weeks that follow, including webinars, telephone conferences, seminars and more. Maybe your own oncologist will be at ASH. Take advantage of these resources and become your own best patient advocate.  

Ready for 4.5 days of information,

--Jack Aiello