The ASH21 Meeting of blood diseases is in the books. What I can share with patients, care partners, and all who are interested is that the myeloma research world is on fire! There are so many new questions for new and veteran researchers, so many creative possible solutions were a part of this annual meeting with a usual attendance of 30,000 health professionals with interests in hematology.
I wanted to share the many advancements being made in the myeloma world – to be able to communicate hope for treatment options and high hopes for a cure for multiple myeloma (MM). There was something new at every level of myeloma treatment — from the newly diagnosed to those who are considered to have relapsed/refractory multiple myeloma (RRMM).
There were an incredible 879 myeloma-related abstracts submitted to the conference — a compelling evidence of increasing interest and progress in this rare cancer by researchers from all over the world. This was a huge increase compared to the number of myeloma abstracts during my first ASH conference 7 years ago in 2014.
The science was sometimes difficult for me to follow, but I knew I would have several opportunities, including leaning on team members to try to understand the mechanisms of new therapies. I knew that I should not get distracted by trying to follow p-values, levels of significance or by understanding the intricacies of targeted therapies. These targeted therapies are moving us closer to precision or personalized medicine. I could gain better understanding of the biology of multiple myeloma and the new strategies to control it.
Some outstanding advances included the seeming omnipresence of the monoclonal antibody, daratumumab, in many therapies – both front line and after three or four therapies. Daratumumab was approved by the FDA in 2015 along with three other drugs. It is interesting to see it taking center stage in combination with various other drugs. The evidence of several clinical trials shows that there may be a change from the current “gold standard” of newly diagnosed myeloma therapy —from three drugs to four drugs.
Population Studies and Biologic Determinants of Myeloma Control
There were several important progress reports on two population studies, one of which is the iStopMM Study (Iceland Screens, Treats, or Prevents Multiple Myeloma) —a part of the Black Swan Research Initiative (BSRI) of the IMF. In this innovative nationwide, randomized clinical trial (RCT), approximately 80,000 adults over 40 years of age who consented to participate were screened for the myeloma precursor monoclonal gammopathy of undetermined significance (MGUS). There were an impressive eight presentations from this clinical trial, including four oral and the remainder poster presentations. One of the significant results is the occurrence of MGUS, expected in the general population as they increase in age. Smoldering multiple myeloma (SMM) incidence was higher than expected. Observations have determined that the use of mass spectrometry versus Serum protein electrophoresis (SPEP) should be used to determine myeloma protein levels.
Because of this unique longitudinal trial, there is genetic sequencing information on all volunteer participants. Finding SMM during screening can allow earlier intervention. The question arises as to whether widespread screening is advisable. The ethics of screening without having an appropriate treatment plan needs to be considered. The results of the studies that come from this trial are highly significant, but come with the limitation of being a homogeneous, virtually all-white population.
Early results from another population clinical trial called the PROMISE Study were presented. In contrast to the demographics of the iStopMM study, the PROMISE Study enrolled myeloma patients 40 and over who self-identified as African American or Black and patients of any race who had a family history of myeloma.
Over 7,200 were screened using SPEP and mass spectroscopy. Overall, MGUS was detected in 10% of volunteers using mass spectroscopy, 6% using SPEP. Some subgroups showed even higher prevalence of MGUS, like African Americans over age 50 with 17% MGUS using mass spectrometry. Clearly, these population studies with different demographics —age, race/ethnicity, geography, genetic sequencing, etc.— will help us unravel the many mysteries of myeloma.
New Approaches to Myeloma Control
Other study results focused on immunotherapy called CAR T therapy, including ABECMA® (idecabtagene vicleucel). On March 26, 2021, the FDA approved idecabtagene vicleucel (also called ide-cel), which targets B cell maturation antigen (BCMA) protein that lives on the myeloma cell. There has been so much work since this therapy was first introduced to reduce major side effects and the expense of CAR T as major barriers for access to this therapy.
The reported outcomes demonstrate remissions that are deeper and last longer, allowing patients and their families a longer period of no treatment. With these advances, there was discussion among some scientists that someday CAR T therapy might replace stem cell transplant as a consideration for earlier therapy than after four prior treatments.
Another major area of research and hope for those who have already been heavily treated for myeloma is the research of bispecific antibodies – an emerging immunotherapy. Bispecific T-cell Engagers (BiTEs) are antibodies that simultaneously target BCMA or other proteins, GPRC5D, and FcRH5 and immune effector cells (like T-cells). Research on all these therapies is ongoing with reports especially on working to decrease side effects like cytokine release syndrome (CRS), cytopenia, and infections.
Social Determinants of Health
I was excited to witness more attention being given to the equally important Social Determinants of Health (SDoH). With all the bench research, and phases I-IV of clinical trials, translating that research to delivery of results to patients and communities must also take center stage. I was encouraged to see the Anti-Racism Studio as a part of the daily agenda at ASH. I believe this heightened awareness of the need for diversity in clinical trials and suggestion from the audience could move the inclusion of diversity in research to a policy level at these scientific sessions. We have to include community engagement in the recruitment of “partners or participants,” not “subjects” to clinical trials. We have to learn from studies like iStopMM and take the clinical trial to the community to remove barriers to participation, such as transportation. We need to consider institutional racism and unconscious bias on the part of providers to be successful in equitable access to care. We should find ways to ensure that all myeloma patients will have access to newly discovered therapies —removing yet another potential barrier to participation. Acknowledging and monitoring for health equity is essential.
I am honored and humbled to be a member of this patient advocate team. It still melts my heart each time I see and hear a researcher-presenter include patients and participants in their acknowledgments. I extend my sincerest appreciation to the IMF and all the sponsors who supported our attendance at this very important annual ASH meeting.
The diagnosis of multiple myeloma is just that — “multiple.” There are so many manifestations of this one diagnosis that you could have 10 people with multiple myeloma in a room and you could hear 10 different versions of their diagnosis and treatment.
Modern treatment options continue to improve progression free survival (PFS) and overall survival (OS). This was nicely reviewed by Dr. Bharat Nandakumar (Mayo Clinic —Rochester, MN) in his Paper Number: 119: Mortality Trends in Multiple Myeloma after the Introduction of Novel Therapies in the United States
All patients with multiple myeloma (MM) diagnosed between January 1, 2004 and December 31, 2018 seen at MAYO and followed in SEER (18 registry research data 2000-2018, November 2020 submission) were included in the study.
Patients were grouped into three 5-year groups based on the year of diagnosis:
For the estimation of relative survival, patients alive at the end of 2019 were censored to align with the published United States general population rate tables.
Overall survival (OS) estimates were calculated by Kaplan and Meier method.
Steady improvement in OS in both populations with time.
Steady decrease in early mortality in both populations with time.
Improvements in survival across all risk groups with time.
Older patients (>65 years) with favorable disease characteristics experienced survival outcomes comparable to US general population – ‘Functional cure.’
Are patients seen in community settings lacking behind in the adoption of available therapies or lack access to them?
However, effective treatment options remain very limited for high-risk variants (HRV) of myeloma such as extramedullary disease (EMD), especially with organ manifestation, and 1q+ and 1q amplification. There is increasing interest in addressing this unmet need. I will share a few of the abstracts that looked at these HRVs.
Paper No: 485: Characteristics and Outcomes of Newly Diagnosed Multiple Myeloma Patients with and without Extramedullary Disease after Autologous Transplant and Maintenance Therapy: A Study from the Cmwp-EBMT. Dr. Nico Gagelmann (University Medical Center Hamburg-Eppendorf — Hamburg, Germany)
EMD is when myeloma cells develop in tissues outside of the bone marrow and can happen at diagnosis or as part of relapse/progression. EMD is less common in IgA MM, but more common in ISS (International Staging System) Stage III. Use of post-transplant maintenance was the focus for this subgroup analysis. In short, PFS and OS was shorter in this subgroup of organ involved EMD regardless of choice of maintenance with thalidomide, lenalidomide or bortezomib.
The effects of the addition of daratumumab are yet to be analyzed. EMD, especially organ involved, remains an area of unmet need where further investigation into effective therapies for PFS and OS is needed.
Paper No: 467: Impact of Chromosome 1 Abnormalities Among Patients with Newly Diagnosed Multiple Myeloma: A Subgroup Analysis from the Endurance (ECOG-ACRIN E1A11) Trial, Dr. Timothy M. Schmidt (University of Wisconsin —Madison, WI)
77In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present from the Diagnosis in Tiny Undetectable Subclones – Herve Avet-Loiseau, MD, PhD,(Universite Paul Sabatier —Toulouse, France)
Dr. Avet-Loiseau asked the following questions: Are abnormal clones present earlier than currently identified? Do these minor subclones impact clinical evolution?
The progression free survival (PFS) and overall survival (OS) were essentially the same for those who did not present but had 1q+ at time of relapse. It is believed this subclone already had an impact on outcome. The significance is that we need to look for this subclone at time of diagnosis to address proper therapy at time of diagnosis.
There are many unmet needs in myeloma therapy. These HRVs are just a couple. Having “extra”-medullary disease or “extra” copies of chromosome 1 are not favorable.
Each year I attend the ASH meeting, I am inspired and thankful there are so many scientists and clinicians that work extra hard to improve diagnostic testing, develop new drugs and combinations of therapies. In this respect, “extra” is important.
I want to send an “extra” thank you to the researchers, the research coordinators, the clinicians, and the patients for their “extra” contribution that will help us one day find a cure for myeloma. Without the “extra” effort by so many, we would not be where we are today in improving survival. But we are not done, and we need to go the “extra” mile(s) to get there.
Until next year, when we learn the newest updates at the 64th annual American Society of Hematology meeting, please stay safe, stay hopeful and be good to yourself and others.
“You have power over your mind – not outside events. Realize this, and you will find your strength.”—Marcus Aurelius, Meditations
As the 63rd annual meeting of the American Society of Hematology (ASH) wrapped up this week, I am looking to the future with hope and excitement. I admit my brain is a bit tired from trying to process all the technical data, but I am trying to have power over my mind!
Since I have relapsed twice in my 10 years of living with multiple myeloma, I tend to be very interested in any studies or information pertaining to my options at relapse. This chart shows that there are many options and combinations available.
This year’s ASH had many updates on key clinical trials. Many of the trials were for heavily pre-treated patients who are running out of options. My other teammates have summarized this information better than I could. However, there was one presentation by Dr. Thomas Martin (UCSF Helen Diller Family Comprehensive Cancer Center – San Francisco, CA) with an update on the CARTITUDE-1 trial that got my attention. This is a study of a B cell maturation antigen (BCMA) directed CAR T-cell therapy called Ciltacabtagene autoleucel (cilta-cel) for heavily pre-treated, relapsed/refractory multiple myeloma patients. When Dr. Martin took the stage, you could see the excitement in his face. He was excited to present the data but more importantly, I think he was happy to be there, presenting to his colleagues who were able to attend in-person.
At the International Myeloma Foundation (IMF) Best of ASH presentation, Dr. Brian G.M. Durie (IMF Chairman of the Board) commented that cilta-cel could have FDA approval by the first or second quarter of 2022.
Last year’s ASH was all virtual. I watched everyone make their presentations virtually. And it is just not the same. Even though we were virtual this year, you could sense the excitement from those who were there in-person during their presentations in front of colleagues.
For those able to attend this year’s ASH in-person, it must have seemed like a family reunion. So many doctors tweeting out pictures with friends or colleagues whom they haven’t seen in 2 years. And all these myeloma doctors and researchers from all over the world work so hard to find ways to treat and hopefully, cure multiple myeloma one day. I am in awe of what they do, and I am deeply grateful for their dedication.
Finally, I was amazed by the Support Group Leaders’ participation in the International Myeloma Foundation’s (IMF) ASH team this year. As I go back and read their blogs, I was amazed at the diversity of the topics. I urge you to take some time to read their blogs. They are all so very interesting, and all from a slightly different point of view. That’s what makes us a great team!
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 …”
Today’s blog will be my last #IMFASH21 blog. As I gather my thoughts after the exhausting but inspirational ASH program, I find myself filled with deep gratitude for research, resources, and the friendships formed along the way.
ASH is filled with the best of the best research in all hematological cancers. There were 879 myeloma-related abstracts at ASH this year. Thank you, researchers! I remember when we first started going to ASH in the early 2000s, there was only a one-page listing of myeloma abstracts presented.
The IMF is developing the first definitive cure for myeloma. Led by the world’s foremost multiple myeloma experts, the Black Swan Research Initiative (BSRI) is pioneering the way for discovery.
The IMF has numerous educational programs and resources that surround ASH that I’d like to ensure you have all the links to. If you were not able to participate on the live programs, below are all the replays. Learn and feel the hope for our futures!
The IMF’s International Myeloma Working Group Breakfast meeting. Thank you to each and every one of these members for checking their ego at the door and doing good work for all of us. Myeloma has no borders!
The ASH IMWG Conference Series is always a lively discussion on the forefront of the future of myeloma research and care. Leading myeloma experts discuss the latest drug therapy and focus on highlights from the 879 myeloma-related abstracts.
Last, but not least: the highly anticipated and valued, IMF Best of ASH. Dr. Brian G. M. Durie discusses important myeloma takeaways in language that patients and caregivers can understand.
When my husband, Michael was diagnosed in 2000, the word “gratitude” was not on the tip of my tongue. However, over the years, we’ve seen many silver linings and layers of goodness. Since I began working for the IMF in 2005, it’s been my great pleasure to work with and to form many wonderful friendships in the myeloma community: the IMF staff, myeloma doctors, researchers, nurses, pharmaceutical/healthcare folks, and so very many cherished myeloma support group leaders, patients, and care partners.
This year’s #IMFASH21 Team has been exceptional. Every year, the team becomes connected like a family. These bonds will forever keep us together in spirit and friendship. To Jack Aiello, Sheri Baker, Yelak Biru, Becky Bosley, Jessie Daw, John Deflice, Linda Huguelet, Sue Massey, Teresa Miceli, Gail McCray, Michael Tuohy, and Jill Zitzewitz — I am grateful for your care, compassion, and dedication, but mostly your friendship. Thank you for being on the Team and for taking your time to help others.
Wishing you Good Health, Peace, Love, and Laughter in the New Year and Always.