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There's No Place Like Home

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As Dorothy so correctly exclaimed, "There's no place like home." After a good night's sleep needed to catch up from an extraordinarily busy ASH, I thought I'd provide some final thoughts.

I've always said the good news about being diagnosed today with Myeloma is that there are so many more treatments available than when I was diagnosed in 1995. And it's never been truer after seeing more options presented at this year's ASH. Of course, the "bad news" about being diagnosed with MM today is there are so many treatments without knowing which works best for you. There's lots of overall statistics with details about responses according to different MM risk groups and other factors but nothing that says "this is the best treatment for you". However, the good news is that if a treatment is going to work, patients typically will show a response in 1-3 mos (cycles). If you're non-responsive, then try another treatment...i.e. manage your disease.

While it's believed that deeper responses lead to longer progression -free survival and overall survival, that's again part of "overall averages." I had a near complete response from an old induction treatment called VAD and a complete response from a tandem auto transplant...however, the response only lasted 18 months, after which I relapsed. Stay educated and try to consult with an MM expert whenever possible.

What I saw at this year's ASH was a better understanding of why patients either relapse (treatment stops working) or are refractory (treatment never worked). Even though Velcade and Revlimid protocols show high response rates, most patients still relapse. This year's meeting had several presentations identifying resistance mechanisms and pathways associated with these drugs. That's why Vorinostat plus Velcade might work in a patient refractory to Velcade. Or why R/R MM patients respond better to Elotuzumab plus Revlimind plus Dex than R/R MM patients respond to Rev plus Dex alone. Or why adding Perifosine to Velcade plus Dex shows responses in patients refractory to Velcade. It's all about "synergy" of drugs combinations used to treat MM, where combining drugs produce better responses than the sum of responses each drug yields.

And the other thing I learned is that not all IMIDs (Thalidomide, Rev, Pomalidomide), Proteasome Inhibitors (Velcade, Carfilzomib, Marizomib), HDAC Inhibtors (Vorinostat, Panobinostat), etc are alike even though they fall within the same category of drugs. As such, one could be R/R to Velcade but Carfilzomib may work...and I presume the reverse could also be true. There are different underlying cell interactions in these drugs even though they fall in the same general category.

Finally, treatment phases of induction (first-line treatment/s), SCT transplant (or not, early or late), consolidation (or not) and maintenance (if so, how long) all continue to be areas of study for newly diagnosed patients. Clinical trials typically begin with R/R patients and then move towards newly diagnosed patients. I think it's so important to enter a clinical trial if you have the opportunity. Typically a trial (especially phases II or III) offers you the best treatment, medically you're monitored very closely, and perhaps it's actually more affordable. Most important, it's the way we advance treatment options for ourselves and future MM patients.

I hope I get a chance to blog from next year's ASH in Atlanta. In the meantime, I'm spending most of the next 2 days pulling together all of my notes for presentation to our SF Bay Area MM Support group. If you want a copy, just reply to the blog with your email information or contact me through the IMF.

Thanks for reading,

Jack Aiello

Monday's Highlights

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It was a long day today with meetings beginning at 7am and ending at 6pm. There were a couple of 1-2 hr breaks in the middle that provided me time to check out posters. And then tonight I attended a Journalist Workshop where MM experts Drs. Durie, Moreau, Richardson and Orlowski presented ASH highlights to the US and International Press that was translated real-time into 4 other languages and also streamed on-line. So let me provide some of today's results working my way backwards.

At the press meeting, the doctors were asked about the most significant announcements at ASH. The various drugs getting the most attention (and well-deserved) were Carfilzomib and Pomalidomide. Maybe you've heard of these and the hope is they'll receive FDA approval in 2012. However, you may not have heard of Elotuzumab (humanized monoclonal antibody) or MLN9708 (oral proteasome inhibitor) which also received positive marks.

Dr. Durie also noted that the treatment paradigm has changed since 10 years ago when novel drugs such as Thalidomide and Velcade started appearing. In the past a patient would receive a limited cycle of drugs, get a transplant or not, and see how they do. Today continuous therapy (at least fairly long-term) is becoming the model. A patient receives induction therapy, a transplant or not, possibly consolidation treatment followed by maintenance. And while it's not known how long maintenance should last, trials are being done for 1-yr, 2-yrs, 3-yrs or even "time to progression" (till your MM becomes active again).

Some exciting trial results presented today include:

  • The oral proteasome inhibitor MLN9708 in Relapsed/Refractory MM pts in a Phase I trial showed about a 13% ORR (<= Partial Response) and 60% stable disease as a single agent.

  • Elotuzumab, which doesn't really have much MM activity on its own, is combined with Rev-dex in a Phase II trial of R/R MM pts and shows a 92% ORR (14% CR) whereas Rev-dex alone showed about 60% ORR for the same type of patients.

  • In the completion of a Phase III trial, Melphalan+Prednisone+Rev followed by Rev maintenance for newly diagnosed older (non SCT eligible) pts showed ORR of 79% and after 4 years, the median Overall Survival (OS) has not yet been reached. Remember, this is an older patient base.

  • BTW, in the same elderly population, Vel-Thal maintenance after VMP or VTP showed 46% CR and median OS not yet reached at 5 years.

  • Several Carfilzomib (Cfz) studies were presented:

    • CfzRd for newly diagnosed showed ORR = 100% after several cycles;
    • Cfz-only for R/R MM pts (not having taken Velcade) showed ORR 42-52%
  • Several Pomalidomide (Pom) results were also presented:

    • Pom-Cytoxin-Prednisone for R/R MM pts showed ORR 66%;
    • Pom-Biaxin-Dex for R/R MM pts showed ORR 60%;
    • Pom-Dex for R/R MM pts (75% refractory to both Vel and Rev) showed 32% ORR with little difference among various refractory groups

And still there was more with drug such as Perifosine, Panobinostat, Vorinostat as well as other combinations.

That's it for Monday's sessions highlights from my perspective. The show ends tomorrow and I'll try to put up one final post after I return home.

Jack Aiello

Sunday, Onyx and Posters

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I only attended a couple of presentations today, both concerning unrelated donor transplants. The first showed that in various area of the world there's significantly less GVHD in areas like Japan and Scandinavia as compared with N. America. The second examined peripheral blood stem cell transplants (PBSCT) vs Bone Marrow transplants, showing Chronic GVHD higher in PBSCT (53%) compared with BM (42%). However the PBSCT method (about 75% of today's transplants) showed benefits in other areas (e.g., better engraftment and better overall survival at 2 years). Since unrelated donor transplants (allo's) are rare for most MM patients, this information is not particularly relevant but still interesting to me.

So I thought I'd talk about a meeting I had with Onyx (Carfilzomib). They are building their Patient Services group and wanted feedback from MM patients such as myself and others. In addition to providing some financial help that will be income-based rather than asset-based, their goal is to address the patient (and caregiver's) complete experience. With direction from oncology nurses on staff, patients will be connected with orgs such as the Cancer Support Community (51 locations in the US, aka Wellness Center) for help with mental and physical well-being. Or a patient may be connected with the Chronic Disease Fund for transportation and logistics services. Or finally patients might be connected with IMF, MMRF, and LLS for medical-related help. We provided lots of feedback and suggestions but I'd say we were all impressed with the goals that Onyx has laid out for themselves to develop an integrated approach to support.

Over the last 2 days I've also looked at many posters with research details, a few I've listed below:

  1. Another example of synergy by combining Revlimid (expresses HM1.24...this isn't good) with AHM, an anti-HM1.24 antibody and helping an initial set of 4 relapsed/refractory (R/R) MM patients.
  2. In 30 R/R MM patients, ARRY-520 shows durable responses in this Phase I trial. And in a Phase II trial of 32 patients, there was single-agent activity (13% Partial Response (PR)). So this will be combined with Dex, Vel + Dex, and Carfilzomib in future trials.
  3. The protocol RVD -> SCT -> RVD (2 cycles) -> R maintenance in a Phase II trial shows 52% Complete Response (CR) and 94% Overall Response Rate (ORR). This represents a 10% improvement in CR (3% improvement in ORR) over CR and ORR at the end of the SCT.
  4. Velcade-Bendamustine-Dex (VBD) showed ORR 58% in R/R MM patients (57) including those R/R to Velcade (ORR 58%) and Revlimid (ORR 50%). In another trial of 40 R/R MM pts, VB (but no Dex!) showed a 47% ORR.
  5. Response rates to Carfilzomib were comparable in R/R MM normal-risk patients (158) with high-risk (at least one of del13, hypodiploidy, del 17, t(4:14), or t(14:16) risk factors) patients (71)
Are your eyes glazed over yet? Mine are. And to think tomorrow is referred to as "Myeloma Monday" when trial results are presented for many new potential MM drugs and regimens. Gotta get a good night's sleep since presentations run from 7am till 6pm.

A bit tired,
Jack Aiello

Saturday's presentations were similar to yesterday...that is, nothing new was announced and even the presentation title was similar: Controversies and Updates in MM. The presenters were MM expert docs Sergio Giralt (Memorial Sloan Kettering-NY), Donna Reece (Princess Margaret Hospital-Toronto) and Ken Anderson (Dana Farber-Boston). Dr Reese focused on induction and maintenance treatment, ie the front and back end of treatment. She stated that the "Depth of response usually correlates with benefits measured by Event-Free Survival (EFS) and Overall Survival (OS)." This belief explains why RVD induction and either Velcade consolidation (twice/wk) and maintenance (once every 2 weeks) or Revlimid maintenance are being evaluated in clinical trials. She also summarized secondary cancers (perhaps a 4-8% increased risk) as a concern being looked at very carefully. It appears the secondary cancers showed up early so perhaps patients were pre-disposed to it even before maintenance. And as my fellow patient, friend and doctor Jim Omel points out, "The chances of MM returning are much higher than getting a secondary cancer."

Dr Giralt spoke about the role of transplant and began by stating "There really are multiple [types of ] myelomas...should they all be treated the same?" He noted that while SCT's still show a benefit when compared with non-SCT regimens such as Melpalan-Prednisome-Revlimid (MPR), after 2yrs (OS 90% vs 87%), it's close. And it's why a new trial between France and the US is accruing patients who will compare RVD followed by a transplant or not to help answer questions about transplant benefits.

It's always a pleasure for me to listen to Dr Anderson, who always is so positive about the progress being made in treating MM. I counted between 20-25 new drugs beyond Carfilzomib and Pomolidomide which he spoke about enthusiastically. And these are drugs that are complementing each other at the cellular level. For example, did you know that as good as Velcade is, it also enhances AKt expression (this is bad)? So combine it with an AKt inhibitor such as Perifosine and you get a synergistic benefit. He ended by saying that genomic profiling of patients over time will be necessary for personalized medicine because changes occur..."the best is yet to come". If you ever get a chance to see or listen to Dr Anderson, please do so...I'm sure the IMF will interview him for their ASH updates.

Speaking of the IMF, this afternoon I attended a presentation on how we individuals can get more involved in legislative issues that benefit us. It's easy...just go to their website's Action Center to get involved and make a difference! And tonight I attended an IMF Media Reception followed by a Grants Award Reception where the IMF announces grant awards to various researchers. It was very exciting seeing young researchers investigating myeloma treatments which may make a difference in our future lives.

Here's to young, creative, brilliant minds...

Jack Aiello

Just some quick background...I was dx'd stage III Myeloma 17 years ago. Now 3 transplants later (one a full allo), a couple of clinical trials, radiation and 3 yrs of graft-versus-host disease (GVHD), I've been in a good remission with no treatment the last 9 years. I've been fortunate to be able to attend the ASH conference each of the last 6 years and am happy to summarize what I've learned (or been reminded of) each day.

ASH is attended by 25,000 hematologists, oncologists, and researchers from all over the world and focuses on providing current treatment options and developments for all blood cancers (leukemia, lymphoma, and myeloma). Most of the exciting new updates on MM clinical trials won't be presented till Monday but there's certainly lots going on before then. Exhibitors such as Celgene (Thalidomide, Revlimid, Pomalidmide), Millennium (Velcade), and Onyx (Carfilzommib) as well as non-profits such as the IMF will be exhibiting their information tomorrow. And each day several hundred posters displaying new findings are displayed.

Today (Fri) is always a day of symposiums preceding the official opening of the ASH meeting. As such, organizations like the IMF and MMRF bring in a panel of MM experts to present and discuss case studies. MMRF ran their symposium from 7-11am this morning and it was chaired my MM expert Dr Paul Richardson. And the IMF symposium chaired by Dr Brian Durie ran from 6:30-9:30 this evening. Each audience was about 500-700 of mostly doctors listening to the current treatment options and controversies that still need further research. Answers to questions such as:

1) How important is a Complete Response

2) Should a Stem Cell Transplant be done sooner, later or not at all

3) What about maintenance treatment?

On the other hand, I heard some great quotes from MM experts. Dr. S. Vincent Rajkumar said "Each year at ASH the number of MM drugs multiply and there are some I can't even pronounce," Or Dr. Antonio Palumbo remarked "Concentrate your best treatment (e.g. combination therapy rather than single agent) as early as possible (which also saves $$ in the long run.)" Dr. Phillippe Moreau pointed out the VGPR (Very Good Partial Remission) from an SCT (Stem Cell Transplant) will still benefit from consolidation therapy (e.g. Velcade-Thalidomide-Dex) followed by maintenance treatment. And all agreed that maintenance treatment should be continued until either the disease comes back or toxicity/QOL becomes an issue.

All agreed the MM is a very heterogenious disease, something we patients already see when treatment responses vary from patient to patient. However, I'm excited by the outlook for personalized therapy for MM patients. It's already starting as patients are being classified, based on cytogenetics and FISH analysis, to standard, intermediate and high risk patients with treatments varying accordingly...but still lots to research from these results as well as gene expression profiling data and more.

Well, that's enough for today.

Keep battling,
Jack Aiello


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