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.
“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!
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]
December 13, 2021 – Today was the final day of ASH but it was still full of information, and to be honest, I’m a bit brain-fried. The day began with the IMWG Conference series (with the replay available on the IMF website). I jotted a few quotes that I found interesting:
IMF Chairman of the Board Dr. Brian G.M. Durie noted that he expects “mass spec will be rolled out in the next year or so.” We’ll see it as a blood test called “Exent” from The Binding Site, which designed the original free light chain test. For many, the results on Exent may be used instead of minimal residual disease (MRD) testing via a bone marrow biopsy.
Dr. Thomas Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA) remarked: “We at UCSF are considering 4-drug therapy Griffin (dara + RVd) to be the new standard of care for transplant-eligible multiple myeloma patients, pending insurance coverage for the dara.”
Dr. Maria-Victoria Mateos (University of Salamanca — Salamanca, Spain) commented: “CELMoDs such as iberdomide will replace immunomodulatory drugs (IMiDs) Revlimid® (lenalidomide) and Pomalyst® (pomalidomide).”
Dr. Martin: “We’ve seen poor responses to the COVID-19 vaccine for patients on anti-B cell maturation antigen (anti-BCMA) and anti-CD38 treatments, but some patients have efficacy after their booster shot. Stopping CD38 treatment for a period of time doesn’t appear to improve booster benefit.”
And now for a few of my takeaways from today’s ASH (all treatments for relapsed/refractory multiple myeloma (RRMM) patients unless otherwise noted:
Dr. Jonathan Kaufman (Winship Cancer Institute, Emory University — Atlanta, GA) presented early results from a trial comparing venetoclax plus dara and dexamethasone (VenDd) vs Velcade®(bortezomib) plus dara-dex (VenDVd) for RRMM and found an overall response rate (ORR) improvement of 20+ points (87% vs 63%) 
This study examined outcomes of RRMM patients (pts) following treatment of bispecific antibodies and concluded for N=57 pts that getting another T cell directed therapy significantly improves median progression free survival (PFS) (mPFS:19 vs 2 months) and OS (NR vs 12 mos) 
For clinical trials, it was proposed that PFS and QoL measures be co-primary endpoints rather than just PFS since many MM patients favor one over the other. 
Dr. Sham Mailankody (Memorial Sloan Kettering —Commack, NY) presented another CAR T study of MCARH109 that targets GPRC5D (not BCMA) and CD3, and eligible patients included those with prior BCMA therapy (inc CAR T as well as allo-SCT). N is small at 16 but 69% had ORR (inc 25% CR) with similar ORR for prior BCMA/CAR T. 
For N=55, this bispecific called elranatamab from Pfizer achieved 69% ORR at the recommended phase 2 dosage (RP2D) 
Dr. Philippe Moreau (University Hospital — Nantes, France) presented results of teclistamab, another bispecific, from a study called MajesTEC-1. For N=165, ORR=62%, CR=29%, 9-mos PFS = 59% and MRD- is 17% (10-6). Dosage is .06 -> .3 mg/kg, using a step-up dosing to minimize side effects such as cytokine release syndrome (CRS), which were all grade 1/2. 
The DREAMM-5 study showed that combining Blenrep® (belantamab mafodotin-blmf) with a T cell Co-stimulator Agonist aICOS resulted in increasing single agent Blenrep ORR from 32% to 52% without increasing side effects. 
Another bispecifc ABBV-383 (previously called TNB-3838) targets BCMAxCD3. For N=76 at the RP2D (40mg via IV), ORR was 81% with >= VGPR of 69%, although for triple-class refractory, ORR dropped to 53%. 
Finally, there were a couple of interesting abstracts 665 and 666 that looked at the cost of saving stem cells for a 2nd transplant and the cost /wait times for doing blood draws (CBC and chem panel) before every Velcade infusion as part of RVd treatment. At Mayo Clinic-Florida, only 2% of patients get a 2nd transplant but the cost of harvest and cryopreservation totals $8 million for all their patients (average 4 years storage). And changing protocols to perform blood draws only once per cycle can save $1,500 and 3-4 hours wait time per draw times the number of draws previously done per cycle.
Well, that’s it for 2021 ASH, although I’ll likely created a blog with my final thoughts, as well as a multipage write-up for anyone that wants it. This “virtual” hybrid platform worked for the most part, though I do miss connecting face-to-face with others. Perhaps that will happen at the 2022 ASH in New Orleans.
The last few years, I have been interested and hopeful in the number of types of immune therapies. Immunotherapies aid our own immune systems to help fight infections and attack cancer cells. We want our immune systems to function as normally as possible to find and destroy abnormal cells to possibly prevent or slow the growth of many cancers, including myeloma.
However, we all know that myeloma is smart and tricky. Myeloma cells have ways to avoid the immune system’s ability to destroy them due to genetic changes that make myeloma cells less visible to the immune system.
Dr. Mikhael has created a series of videos to help us better understand:
Harnessing the power of our own immune systems to work best and help it to do what it’s supposed to do is smart science! Bispecifics act as the bridge connecting the T-cells to the myeloma cell. The T-cell then kills the myeloma cell, as it recognizes it as an abnormal cell. These bispecifics are what are sometimes referred to as “off-the-shelf.” This is different than the CAR T immune therapies, whereby a patient’s own T-cells are harvested and then sent to a lab to be re-engineered and then given back to the patient.
This process takes time and the challenge of what does a patient do while waiting for treatment, plus can a patient even get CAR T? We have heard that cancer centers only have a certain number of spots for patients waiting for CAR T. Hopefully, this shortage of spots opens soon to enable more myeloma patients to have access to CAR T.
On Saturday afternoon, we listened to Abstract 161 on “Phase 1b Results for SubQ Talquetamab Plus Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)” by Dr. Ajai Chari (Mount Sinai — New York). This bispecific is a little different because instead of targeting B-cell maturation antigen(BCMA), it targets G protein-coupled receptor, class C group 5 member D (GPR5CD). This is important for patients who have already had multiple BCMA targeted therapies, because it’s a different target to go after besides BCMA. More Targets = More Hope!
Here are a few slides on SubQ talquetamab plus dara:
The title of today’s blog is “I Hope Myeloma BiTES the Dust” and here’s my song for you to enjoy by Queen: