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Highlights Of The 2014 International Myeloma Working Group Annual Summit

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Published: Jun 26, 2014 1:06 pm

The 2014 International Myeloma Working Group (IMWG) Annual Summit took place in Milan, Italy on June 9 and 10.

The summit is a special meeting organized by the International Myeloma Foun­da­tion in which leading myeloma researchers get to brainstorm col­lectively about the most pressing issues in the field, find ways to col­lab­o­rate, and plan future laboratory and clinical studies.

The IMWG summit is hailed by most attendees as the most important meeting for myeloma researchers worldwide. It is a unique opportunity for investigators in the field to engage in lively debate but, at the same time, learn new and often differing points of view.

All of this is important as we strive to do what is best for our patients and make further progress in the diag­nosis and treatment of multiple myeloma.

Some of the highlights of the meeting from my perspective are listed below.

  1. We will be coming out with revised diagnostic criteria for myeloma that will allow earlier treatment be­fore end-organ damage.
  2. The IMWG is standardizing minimal residual disease (MRD) assessment, and a highly sensitive flow cytometry method is being prepared for implementation soon. We are glad that there is agreement in the myeloma community to move forward on this issue.
  3. Dr. Antonio Palumbo of the University of Torino in Italy is leading the charge in the development of a frailty index for myeloma and specific recommendations for modification of therapy that take into ac­count a patient’s age and other health problems. Work related to such an index was presented dur­ing the most recent American Society of Hematology annual meeting (abstract and related pre­sen­ta­tion slides).
  4. There was a lively debate on whether melphalan (Alkeran) should remain as an option for frontline therapy given results of the recent FIRST trial. A consensus emerged that there are strong data that continue to support the use of alkylators such as melphalan in frontline therapy as part of many reg­i­mens, but cyclophosphamide (Cytoxan), another alkylator, may be a better option for most patients when an alkylator is to be used in the frontline setting. Melphalan, however, remains a very important agent in myeloma therapy.

    (I included the results of the FIRST trial as #1 in my previous column for The Beacon, “Top 10 Dis­cov­eries Of 2013 In Multiple Myeloma.”  For more on the results of the trial, see this related Beacon news article.)

  5. There is a difference in practice between the US and Europe regarding early versus delayed stem cell transplantation. In Europe, early transplants are favored. In the US, either option is offered depending on various factors, including patient choice. A large ongoing randomized trial this is comparing early versus delayed transplant will provide answers soon in regard to this issue.
  6. A number of new agents are showing promise in myeloma. These include new proteasome inhibitors (marizomib, ixazomib (MLN9708), oprozomib (ONX 0912)), anti-CD38 monoclonal antibodies (dara­tu­mu­mab and SAR650984), elotuzumab, panobinostat, filanesib (ARRY-520), and dinaciclib.
  7. The bone working group decided to collaborate and compile data on how best to use new imaging modalities in the diagnosis and management of myeloma.
  8. There is an emerging consensus that the t(4;14) subset of myeloma should be treated with Velcade (bortezomib)-based initial therapy and maintenance. In addition, the data available show that this subset of myeloma benefits from early transplantation, and we are now discussing whether selected patients may also benefit from tandem auto transplants.
  9. There was a good discussion on the current status of immunotherapy for myeloma. We are looking forward to more data from ongoing trials.
  10. As expected, there was a lot of discussion about the recent measles vaccine news, and my Mayo Clinic colleague Dr. Steve Russell was on hand to explain the plans moving forward. (For more regarding the measles vaccine news, see this press release and the related discussion in the Beacon’s forum.)
  11. One of the highlights of the meeting was the presentation of the Robert A. Kyle Award to Dr. Antonio Palumbo, Dr. Palumbo has made numerous contributions to the field, including leading over 10 ran­dom­ized controlled trials -- a phenomenal accomplishment.

A lot more happened at the summit; this is just an overview. One of the best aspects of the summit is small group discussions, of which there were at least eight. I am sure a lot of new collaborations were formed at the summit. We are already looking forward to the next one!

Dr. S. Vincent Rajkumar is a professor of medicine and chair of the Myeloma Amy­loi­dosis Dysproteinemia Group at the Mayo Clinic in Rochester, Minnesota. His research focuses on clinical, epidemiological, and laboratory research for myeloma and related disorders.

Photo of Dr. S. Vincent Rajkumar, professor at the Mayo Clinic.
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  • R said:

    Thanks !!

  • Nancy Shamanna said:

    Thanks Dr. Rajkumar for this summary and description of the latest research and thinking about myeloma. I think that what stands out to me is how the international community of researchers and clinicians are getting together to 'brain storm collectively', as you say. We as patients can only benefit ultimately from all of this, even though sometimes the world of new research takes time to reach patients.

  • Steve said:

    Muchos Gracias!

  • Mark K said:

    Thank you Dr. Rajkumar.

  • Nicole Racette said:

    Great summary. Thanks to all of you to participate in the working group. This will benefit all of us.

  • Susan said:

    Thank you for keeping us up to date Dr. Rajkumar. I do not know if you have researchers from Australia attend these meetings, but I do feel that we in Australia have brilliant researchers and I hope they are working together with the USA & Europe. The more knowledge that is pooled the better from a patient's point of view!

  • Jan Stafl MD said:

    Thank you Dr. Rajkumar for another useful summary list! A few specific questions please: 1.) Are we closer to being able to clinically check Cereblon levels for IMiB sensitivity prior to Rev and Pom therapy in recurrent MM patients? 2.) Likewise, how about CD38 ab testing prior to monoclonal antibody therapy with Elo or Dara? And 3.) What about the utility and timing of genomic analysis? It seems to me that more targeted therapy may be applied individually based on this testing, such as the BRAF (V600e) and MEK inhibitor therapy that I had a near complete response to, albeit for only the average 7 months.

    Finally, the immunotherapy options and combination novel agent therapy appear to hold the best hope for long term control in our hope for making MM a chronic, controllable disease for most patients.

    I always value your opinion as the most experienced and wise. Namaste! Jan

  • Mark said:

    Thanks for the excellent summary and the great job you do of keeping myeloma patients informed of the latest news.

    I just want to make a quick comment with respect to points 8 and 9. I am a younger (early 40's at diagnosis), high risk patient and I am doing extremely well 3 years after doing an allo transplant in first complete response. The only pharmaceutical drug I currently take is zoledronic acid [Zometa] due to extensive bone damage and my quality of life is back to normal other than the bone damage I had at diagnosis. I currently have no GVHD. IMO the myeloma doctors that are not skilled/comfortable with allo transplants should be encouraged to refer younger patients to doctors that do allo transplants so more younger patients get the opportunity I was given. My experience with immunotherapy for myeloma has been extremely positive.

  • Sylvia B said:

    Dear Dr. Rajkumar,

    Thank you for the information. As an mm patient, I really appreciate the up-to-date report as it gives me such hope. I see that many doctors and researchers are working hard on helping people live good quality lives with mm.


  • marvin said:

    Dr. Rajkumar

    I want to add my thanks. As a mm patient, I can't get enough info about our disease and treatments for it. Your articles are always appreciated.


  • Jan Stafl MD said:

    Hello again, Dr. Rajkumar. I have one more burning question, as it is a therapy I am considering as a trial. Any mention of CAR-T therapy, which seems so promising for many hematologic cancers? Thank you. Jan

  • S. Vincent Rajkumar, M.D. (author) said:

    Thanks for the comments. I am not sure about whether we are closer or not as far as testing for cereblon expression. I know Dr. Keith Stewart is working on it. Having an assay that is up to certification standards is a hard process. Further, we need more data on how such information works in terms of positive and negative predictive value in practice.

    CD38 is almost always expressed by plasma cells, so no need to test. Elotuzumab targets CS1, not CD 38; daratumumab and SAR650984 target CD38. CS1 is also almost always expressed by myeloma cells, so I do not think testing is needed.

    The value of genomic sequencing such as whole exome sequencing or limited commercial panels is not established in myeloma (and as far as I know any other malignancy). Having said that, I think it is worth considering such testing in some circumstances, although realistically the chance of finding an actionable target, where the "action" actually works in a meaningful manner, is very low at present – probably <5%. This number will hopefully increase as we have more new targets and more new drugs. Right now we are considering genomic testing in patients refractory to other treatments and who are not candidates for the available clinical trials.

    I agree about immunotherapy -- promising. Dr. Stadtmauer did discuss the CAR-T therapy and the trial at the IMWG summit. Just need to wait for real data to decide where this goes.

    The IMWG has researchers from all over the world, including Australia! The full list is usually in the Appendix or Acknowledgment section of most IMWG manuscripts.

  • Myeloma Beacon Staff said:

    Just as a quick follow-up to Dr. Rajkumar's feedback directly above ... a regularly updated list of IMWG members is available in this Beacon forum thread:

    "International Myeloma Working Group (IMWG) - Members"

  • Jan Stafl MD said:

    Thank you Dr. Rajkumar for your insightful answers to my queries. You are providing a very valuable service to the readers of Myeloma Beacon with your quarterly column, and it is much appreciated! I do think an important focus of research needs to be on testing to predict the therapeutic response to novel agents and monoclonal antibody therapy, especially in refractory patients. CD19 testing may be warranted with emerging CAR-T therapy. Your comments on genomic sequencing are right on. It certainly made a great difference in my treatment though.

    The IMWG, along with the IMF and MMRF, are making a huge difference in pressing for the need for basic science research, in addition to just the profit driven pharmaceutical company sponsored research. Thank you to the MB staff for providing a list of the IMWG members. I noticed it includes two members from my home country, Czech Republic, Dr. Hájek and Dr. Sevčíková in Brno. Keep up the great work! Jan