The past weekend, October 19-21, the IMF convened the second annual Asian Myeloma Network (AMN) Summit in Beijing. The first AMN Summit was in Seoul, South Korea last October. Members from the seven countries that make up the AMN—China, Singapore, Taiwan, Korea, Japan, Thailand, and the region of Hong Kong—gathered to review and discuss the top strategic priorities for 2018. With a focus on the Asia-Pacific region, the key topics aligned with those presented at the International Myeloma Working Group (IMWG) Summit held in Stockholm in June: CAR T-cell therapy, transplantation, genomics, and minimal residual disease (MRD).
2018 Strategic Priorities
Presentations from global guest speakers and Asian-Pacific experts made it clear that these were hot topics everywhere. With plenty of time for discussion, the input from the global experts, including myself, Professor Jean-Luc Harousseau (Nantes, France), and Dr. Thomas Martin (University of California, San Francisco), was greatly appreciated. And it was impressive to see the comprehensive data now available from Asia. CAR T-cell therapy, for example, is widely available in China—more protocols than anywhere else in the world! Professor Lei Yu of the Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development (ECNU) presented the impressive Chinese experience, including a combined BCMA-CAR T and CD19-CAR T protocol similar to the protocol being initiated by Professor Andrew Garfall at the University of Pennsylvania.
Professor Martin provided an excellent overview of the U.S. experience with CAR T-cell therapies. He emphasized the following:
- The dramatic efficacy of CAR T-cell therapies
- The need to carefully assess the length of remissions achieved, as well as the toxicities, such as cytokine release syndrome (CRS)
- The potential for significant refinements: transition from the “model T” to a Lamborghini type of “CAR.”
- The need for special response criteria, since the early dramatic responses outpace traditional methods of assessing response by measuring the percentage of reduction in m-protein, (as in PR, 50%, VGPR, >/=90%, and CR, 100%).
There is a huge opportunity to explore all of these approaches in China. For example, Dr. Juan Du from Shanghai presented results of a new CAR T-cell protocol in which patients with very advanced disease were already achieving dramatic benefit without significant toxicities. Without diminishing the major efforts in the U.S., there is a sense that China will be leading the way with innovative new CAR T approaches.
Professor Martin emphasized that CAR T therapy is a game-changer in the approach to myeloma management. He discussed how “safe” CAR T therapies can be introduced early, when the T cells harvested for the genetic engineering will be in “better shape” (more functional), and suggested that T-cell infusions could potentially replace traditional autologous stem cell transplant (ASCT).
Of concern in the use of CAR T-cell therapy is the cost. FDA Commissioner Dr. Scott Gottlieb recently sounded a note of alarm. The two CAR T therapies currently on the market cost between $373,000 and $475,000. One proposal is to use “outcomes-based contracting.” But no agreements have been reached. Of note, CAR T therapies are much cheaper in China, costing $30,000 to a maximum of $100,000. Since other expensive novel therapies are not yet available in China, it is possible that the new paradigms incorporating CAR T therapies will evolve more rapidly in China and elsewhere in the Asia-Pacific region.
Genomics, MRD, and Much More
A range of other strategic priorities were presented and discussed. There is considerable expertise in genomics in Asia. Professor Lugui Qui (Tianjin, China) and Professor James Chim (Hong Kong) provided excellent overview presentations. Professor Qui presented results of extensive FiSH testing carried out on approximately 1,500 cases of newly diagnosed multiple myeloma and 321 relapse patients. He particularly emphasized the poorer outcomes in patients with the 1q+ genetic abnormality (an additional lower part of chromosome 1 in myeloma cells), a feature recently gaining more frequent attention in U.S studies as well.
Professor Chim discussed a variety of topics, but ultimately focused on the potential value of molecular/mutational analyses of cell-free DNA in the blood. This is certainly a convenient approach, and is being used by Professor Andrew Spencer and his team from Melbourne, Australia, as part of his Black Swan Research Initiative® (BSRI) project to precisely monitor patients with positive MRD at the molecular level.
Professor Wenming Chen (Beijing Chaoyang Hospital) and I discussed the current status of MRD testing. There is tremendous interest in MRD testing throughout Asia. An action item is to plan a follow-up workshop on MRD in Asia in 2019. There is also a proposal to develop a specific, MRD-testing protocol for patients receiving CAR T therapy.
Professor Jean-Luc Harousseau and Dr. Yao Chen from Peking University Hospital discussed both autologous and allogenic transplantation. Clearly, transplantation remains an important modality of treatment. Potential protocols for the future were discussed.
Work Group Sessions
After the initial opening presentations and panel discussions, the participants broke up into working groups—just as we do at the annual IMWG Summit. These groups turned out to be very productive, and full reports were presented to the group the next morning. Action items for 2019 were discussed, with considerable excitement about the options available.
Professor Wee Joo Chng summarized the ongoing trials being conducted by the AMN group throughout Asia. There has been great progress in coordinating accrual of patients from the seven different countries. Results from the first trial (AMN 001) involving pomalidomide and dexamethasone are now being submitted for publication. With several trials ongoing, new discussions concerned possible AMM 008/9 trials, one to include an anti-CD38 monoclonal antibody, isatuximab. Interest in the AMN is leading to discussions of expanded membership. Representatives from Malaysia were present, and it seems they will be the next to join the AMN trial groups.
Perhaps the most appreciated presentation was given by Dr. Daryl Tan from Singapore, who discussed “Patient Support: Realities of Treatment in Asia.” The realities are, in fact, quite sobering, since many novel agents are either not available or way too expensive to be used by the average patient. Discussed in the context of the difficult options faced by an individual patient, the stark reality of poor access was obvious. Dr. Tan ultimately decided to refer the patient to China for CAR T therapy—certainly a sign of the times!
With this clear wake-up call, the participants were invigorated to become more active and involved to seek the best for their patients. For many patients, the availability of the AMN trial drugs is a true lifesaver.
The second AMN Summit closed on a very high note, with positive expectations for 2019 and anticipation of the third AMN Summit, which will be held in Hong Kong next year. My thanks for all who made this extraordinary meeting such a success, including Lisa Paik (IMF Senior Vice President of Clinical Education & Research Initiatives); Daniel Navid (IMF Senior Vice President of Global Affairs); Amirah Limayo (IMF Research Project Coordinator); Annabel Reardon (IMF Director of Meetings & Events); and Abigail Guzman (IMF Meeting Registration and Guest Relations). Thanks, also, to our local host, Professor Wenming Chen, and the AMN Executive Team members who helped plan the agenda and schedule the event. Guests were hosted at two wonderful Chinese dinners—one included the famous Peking duck. We also had the opportunity to tour the Forbidden City, an unforgettable experience which vividly evokes the time when emperors ruled China.
The year 2018 and beyond is a new era in Chinese history. Without knowing what is to come, it is certain that things are evolving rapidly. We look forward to the many opportunities to come in Asia to expand our knowledge of multiple myeloma treatment and hasten its cure.
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.