This year, the IMF held the usual Best of ASH for everyone to register for free and participate in —with a live Q&A with IMF Chairman of the Board Dr. Brian G.M. Durie. Additionally, the IMF Support Group Leaders had a special Zoom room gathering where all the leaders were invited to join and watch the webinar and have an additional Q&A with Dr. Durie.
Questions ranged from discussion on novel agents and how they are changing treatment for high-risk patients, smoldering multiple myeloma (SMM) and high-risk smoldering multiple myeloma (HRSMM) trials, newly diagnosed multiple myeloma (NDMM) patients and 4 drugs upfront (use the best treatment option available at each stage) and of course, CAR T and bispecifics in relapsed/refractory multiple myeloma (RRMM) and potentially upfront for even better responses.
Dr. Durie presented the highlights from ASH, including six iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) ASH Abstracts, consisting of 4 oral presentations and 2 posters. I’m excited for all the results from this important research, and I am looking forward to additional updates instead of using serum protein electrophoresis (SPEP), or mass spectrometry to measure the myeloma protein as it is so much more sensitive and showing deeper levels of minimal residual disease (MRD) negativity, even at the 10-5 and 10-6!
I look forward to how this will be interpreted for treatment decisions in the real world. Another focus I’m watching for is information on DNA genetic sequencing to help determine genetic features that predispose to monoclonal gammopathy of undetermined significance (MGUS) and progression to myeloma.
When we had the opportunity to be in Iceland to listen to iStopMM updates in 2018 and 2019, the iStopMM team shared insights into the tree; there were a couple that stood out to me:
Flow Cytometry – The iStopMM study is employing Next Generation Flow (NGF) cytometry in the care of individuals with MGUS and those who are diagnosed with SMM and MM. The aim is to be able to use this emerging technology to identify those who will progress to active disease so that their follow-up and treatment can be tailored to them in the future. NGF also gives insights into tumor microenvironment, the cells around the myeloma cells that nurture and support them. Learning more about this crucial part of myeloma development might open the door to new ways of treating or preventing myeloma in the future.
Psychological impact of cancer screening – A part of the iStopMM project is to do deep analysis into the psychological effects of screening for MGUS and how knowing about precursor conditions (that, in most cases, is otherwise harmless) will affect mental health. This information is highly relevant for other cancer screening programs as well.
COVID-19 – The iStopMM team just published a paper using iStopMM data and “created a new branch of the tree” to answer pressing questions for individuals with MGUS —there is no increased COVID-19 severity with MGUS (Abstract #154)
On last night’s Q&A with Dr. Durie and leaders, Dr. Durie stated that Iceland may be a place where we can either prevent or even cure myeloma! Thanks to all the Icelanders for participating in the iStopMM trials!
Of course, we all continue to be excited about CAR T therapy, and as Jack Aiello stated in his blog, “Which CAR to Hitch a Ride with?” Well, CARTITUDE-1 (cilta-cel) continues to impress with excellent Overall Response Rate (ORR) of 97.9% and even more encouraging is the stringent Complete Response (sCR) Median 1-year follow up: 67 and actually deepened over time; Median 2-year follow up 83! (Abstract #549) Remember, these are patients that have been heavily pre-treated. Imagine what the results may be if used upfront in NDMM?
As #ASH21 comes to a close, the research continues on. So, keep on keepin’ on and look to the future with hope and share that hope with others. We’re all in this together.
Thanks to the IMF for being the first to bring myeloma patients/support group leaders to ASH. It’s an honor and privilege to be a part of the Team. Thanks to all the sponsors for supporting this valuable opportunity: BMS, Karyopharm, and Takeda Oncology.
My last song to share with you from #IMFASH21 is “End of the Line” by The Traveling Wilburys.
Fun fact: The name “Wilbury” was conceived in 1987 while Jeff Lynne was producing George Harrison’s “Cloud Nine” album. Whenever there was a mistake, Harrison would tell Lynne, “That’s okay, WE’LL just BURY it in the mix …”
I am so thankful and impressed with the content and variety of topics that the #IMFASH21 support group leaders are reporting through their blogs. Each brings important highlights that will be helpful in Support Group discussions.
For those who do not attend a support group, this information can be helpful to review and discuss with your healthcare team. Staying up to date on myeloma, its treatments, side effects and clinical trials is key to our futures, as we decide on next potential therapies.
My blog today will focus on “Filling in the Spaces” of information from other leader blogs. Yelak Biru wrote an excellent blog on #ASH21 Trial Design Acronyms. Along with that, I thought it would be helpful to add the treatment algorithms below.
Please remember that these are just general recommendations, but they are a good starting point for conversations with your own healthcare team.
New Myeloma or Smoldering Myeloma:
Myeloma: Frontline Treatment
Myeloma: First Relapse
Myeloma: Second or Higher Relapse
Additional Charts that I found helpful:
On the above chart, please note that panobinostat was withdrawn by the FDA in the US but not in Europe.
These algorithms are CURRENTLY the best options to think about but as we all know, things change.
Keep learning, keep sharing, andremember — you are not alone!
More information on the myeloma support groups can be found HERE. You can also contact me at [email protected]
Saturday at #ASH21 was a full day that began at 6:30 a.m. ET, with the #IMFASH21 team being invited to be a “Fly on the Wall” at the International Myeloma Working Group’s (IMWG) breakfast meeting. This prestigious group of over 250 global myeloma specialists meets twice a year to collaborate on projects. They form working groups, give updated status reports, produce guidelines for myeloma treatment, and decide upon new projects. At ASH, they also discuss and preview some ASH abstracts (which are embargoed until they are officially presented at ASH.)
I am both grateful and in awe at the amount of work this group does — and I mean “group.” As Susie Durie often would say: “Their egos are checked at the door,” and they come together on behalf of helping the entire myeloma community — from the general oncologists who don’t have time to come to ASH, to the patients and caregivers trying to keep up with the rapidly changing treatment paradigm. Learn more about IMWG and its guidelines/publications here.
After leaders attended the IMWG breakfast, we went directly into our schedule to view oral abstracts virtually. However, to our frustration, there were technical glitches, and we were not able to view some of the morning abstracts. But as resilient leaders, we will look to the replays. Our virtual badges give us the ability to watch #ASH21 replays until January 1.
I mentioned in my pre-ASH blog that I would be reporting a bit on the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) project in each of my blogs. iStopMM aims to map the epidemiological and clinical characteristics of smoldering multiple myeloma (SMM) in the general population based on a large population-based screening study.
Michael and I have been extremely interested in this project since its inception 5 years ago. This year at ASH, the iStopMM team has four oral abstracts and two posters — quite an amazing accomplishment! I listened with great anticipation, and I continue to be inspired by the results and the selflessness of the Icelandic people in their willingness to volunteer and to participate in this research! Read more in Oral Abstract 151: Prevalence of SMM: Results from iStopMM study Sigrun Thorsteinsdottir MD, Ph.D.
Additionally, refer to oral Abstract 154 on monoclonal gammopathy of undetermined significance (MGUS) and COVID-19 presented by Sæmundur Rögnvaldsson, MD (University of Iceland – Reykjavík, Iceland). This, of course, is of particular interest as we all learn how COVID-19 affects us. For MGUS patients in this large population-based study that included 75,422 individuals screened for MGUS, they did NOT find MGUS to be associated with SARS-CoV-2 susceptibility or COVID-19 severity. This is contrary to multiple myeloma (which is preceded by MGUS). These findings suggest that immunosuppression in MGUS differs significantly from that of multiple myeloma and is important since they can provide information for management as well as recommendations for individuals with MGUS.
Patients were heavily pretreated with 97% triple-class refractory. For me, this was an abstract I had been looking forward to, as it is a new mechanism of action. Cereblon E3 ligase modulator
(CELMoD) is “easy” since it’s all oral. Something to share with my support group members at home that is RRMM.
Saturday was packed with excellent presentations that continue to give us hope and are getting us closer to a cure, with lots of updates on MGUS, SMM, MM, and RRMM. Please read all the other excellent blogs from the #IMFASH21 Team members. Sharing the Hope!
Thanks to all the dedicated researchers. Cheers to your continued hard work that our futures will benefit from!
As with previous years, the International Myeloma Foundation (IMF) held its signature satellite symposium during that 63rd annual meeting of the American Society of Hematology (ASH). It featured Drs. Brian G.M. Durie (IMF Chairman of the Board), S. Vincent Rajkumar (Mayo Clinic — Rochester, MN), Tom Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA), Jesus San-Miguel (Clinica Universidad de Navarra — Navarra, Spain), Philippe Moreau (University Hospital — Nantes, France). Absent this year was Dr. Shaji Kumar (Mayo Clinic — Rochester, MN).
The symposium flow included a hypothetical case presentation, followed by how you treat questions and audience vote, the speakers’ case for why they voted the way they voted, and then audience polling to see if the speakers changed any audience minds.
The case studies and presentations ranged from smoldering myeloma to relapsed/refractory myeloma, approved drugs, drug combinations, and drugs in the pipeline.
I noted on the disclosure slides the only one that did not have ANY disclosures was Dr. S. Vincent Rajkumar. Does it mean the others are conflicted, and you should consider their discussions to be biased? Well, NO! I invite you to read this Twitter thread to see why not.
The significant benefit of treating high-risk SMM patients in myeloma is high, noted Dr. San-Miguel, up to 7 years of progression-free survival (PFS) before the smoldering myeloma progressed to full-blown myeloma. Not only was the progression delayed, but the risk profile post-progression was similar to those on the wait-and-watch approach. Dr. Rajkumar indicated the wait-and-watch experiment has failed for high-risk smoldering myeloma patients.
The speakers noted the features that made SMM high risk (seen below), where the presence of these features indicated an up to 50% chance of progressing to myeloma in two years.
Factors Identifying 50% Risk of Progression at 2 Years
Over the last two years, the researchers consider high-risk indicators have evolved. You may have heard the 2/20/20 model. They are now indicating the potential for the model to evolve to a 2/20/0.02% model allowing for frequent monitoring of the SMM patient and early warning system that the smoldering myeloma will progress to full-blown myeloma. Watch the studies in this area as research has indicated the importance of early intervention pre CRAB.
Circulating Tumor Cells Predict Risk of Progress in SMM Patients
Some exciting questions are being asked: Can CAR T replace upfront high-dose autologous stem cell transplant (ASCT)? Dr. Morreau indicated that a clinical trial is in the design phase in Europe.
Dr. Martin’s wish list for future bispecific antibodies in relapsed/refractory myeloma included outpatient dosing with low cytokine release syndrome (CRS) and neurological toxicity, convenient administration (every 4, 6, 8 weeks). Dr. Martin had a similar wish list for BCMA CAR T cells, including faster manufacturing, better expansion, dual targeting, and outpatient administration.
One of the highlights of the symposium was that all the bispecific antibodies for relapsed/refractory myeloma have a single drug overall response rate (ORR) of over 50%, some even 80%. This high ORR was unheard of in the chemotherapy era and even in the age of novel drugs such as Velcade® (bortezomib), Revlimid® (lenalidomide), Kyprolis® (carfilzomib), or Darzalex® (daratumumab).
Summary of Bispecific Antibodies in RRMM
Dr. Durie discussed the unmet need of triple-class refractory myeloma patients. Those patients, despite all efforts, their myeloma continue to progress and eventually die. He indicated the issue is even more exasperated with the withdrawal of melflufen and panobinostat from the market, and the limited use of venetoclax.
The Unmet Needs of Triple Refractor Myeloma Patients
And finally, Dr. S. Vincent Rajkumar of the Mayo Clinic unveiled his “Treatment Algorithm for 2020”. This algorithm embraces the principle of triplet preference, including at least two new drugs (not sure just drugs or if feasible drug classes), consideration of transplant in patients eligible for transplant. He said, “My preference is for people not to use this algorithm and urge patients to sign up to clinical trials.”
During this symposium, I heard the phrases
Flattening of the curve (the survival curve)
Long treatment-free interval (drug holidays)
Ease of administration (at home and subcutaneous administration, treatment intervals of >2 weeks)
Fewer side effects
There was an acknowledgment by the group that more needs to be done to bridge the gap between what the on-the-ground country by country reality is and the potential these new drugs offer.
The IMF teams will be busy at ASH and will be facilitating either virtual or hybrid meetings:
What an amazing and exciting day that kicked off the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition. ASH allows doctors from around the world to present various studies happening within the myeloma community. It is truly amazing to see all of the developments within this area.
In addition, I am so grateful that the meeting has a virtual component. The virtual element allows me to experience the meeting without missing a beat! If I had to attend in person, I would not be able to go. By still permitting a virtual platform, I’m able to see all the wonderful presentations that are full of the latest and greatest updates on myeloma. What a great opportunity!
Furthermore, I want to thank the IMF for this occasion. By attending ASH, I can gain more knowledge, which I can then provide to the members of the MM Families Virtual Support Group. https://www.myeloma.org/support-group/mm-families The MM Families Virtual Support group empowers myeloma patients and their caregivers who have young children. By hearing all this newfound knowledge, I hope to encourage them on their journey!
To kick off the first day of ASH, the IMF led a wonderful discussion panel which focused on the following: High-Risk Smoldering Patients; Therapeutic Strategies for Newly Diagnosed Myeloma Patients Both Eligible for Transplant and Not Eligible for Transplant; Tailoring Therapies for First Relapse; Managing Triple-Class Refractory Myeloma, and BCMA-Targeted Therapies.
It was so interesting to hear all the discussions and studies on these various topics. One of the most interesting items that I learned was the development in treating high-risk smoldering multiple myeloma (SMM). Wow! How times have changed! While there is still debate on whether to treat SMM or take the “watch and wait” approach, some of the new studies showed so much promise in treating myeloma early. There was also some interesting data on high-risk patients and tandem transplants, as well as discussion between triplet and quadruplet therapies. In addition, there are so many interesting new studies relating to CAR T.