As a Ph.D. with a focus in sport and exercise psychology (Kinesiology, Illinois, 1999), I naturally want to understand thought processes and emotions, and how they influence behavior. As a myeloma support group leader, I also participate in discussions with those on their myeloma pathway. And, as someone diagnosed with smoldering myeloma, I have evaluated (and constantly evaluate) my own pathway from a psychological perspective. This is natural for me, as this is life with a capital “L.” My Life is me — and how I view the world in the course of my pathway, or what I refer to as mindset, impacts my quality of life. It does for others, too.
Sometimes, people feel like things happen to them and they have no control, while others perceive more control in their lives in spite of challenges faced. This can be likened to the phrase of a glass half-empty or half-full, but it goes beyond simple pessimism and optimism. In short, those who lack a sense of control tend to feel like a pawn, as they experience low self-esteem, loss of motivation, and shame. They also tend to shut others out and may also use a lot of comparison behaviors.
In contrast, those who perceive more control act as orchestrators of life, regardless of current circumstances. Of course, unexpected and negative things happen, but they act through these things with a sense of involvement to determine their next best steps. Those with this mindset tend to persist more with health-related behaviors and have better mental health. And while they may listen to and learn from others’ experiences, they don’t engage in a lot of comparison. (Maybe you’ve heard the quote: “Comparison is the thief of joy.”)
With this orientation, I searched for ASH abstracts dealing with mental health. I found papers addressing:
psychological distress, prognostic awareness, and quality of life among patients and caregivers;
exploratory work assessing interest in lifestyle intervention for myeloma patients;
examination of depression, anxiety, and clinical trial perceptions among patients;
impact of a digital life coach during autologous stem cell transplant; and
financial toxicity and its effects on patients and families
Additionally, the iStopMM project reported that it will be assessing mental health longitudinally, and so that data will be highly anticipated in the years ahead.
I found much of this work interesting, and my original intent was to detail these various papers and their findings. But as I write, I’m shifting perspective to more of an editorial nature. As I provided a summary of mindsets above, I have nagging thoughts about toxic positivity along with the roles distress and mental/emotional pain. I think we have to be aware of toxic positivity. This is the frame of mind where negative emotions are dismissed and people think that no matter what, “I must present a positive mindset.” It tries to push aside the difficult emotions, such as fear and sadness, and can be quite harmful to our mental health.
In this Life, how can we help people who are in the midst of what for many is their toughest challenge? How can patients get to a mental space where they recognize and accept their challenge, and also hold a positive mental mindset that provides a healthy energy which helps them deal not only with day-to-day challenges, but also with something that endangers their way of life and, at times, even their existence?
For me, much of the answer is in rejecting toxic positivity and in embracing the full range of the emotional spectrum — from experiencing the high of highs to the low of lows, and being authentic and aware in these moments of life. Yes, in the low times, the heart hurts and feels like it’s breaking apart and is being torn out. We cannot deny these difficulties and must experience them. But how can we help others see that instead of breaking apart, the heart may actually be breaking open? Breaking open to new possibilities, new ways of being, deeper relationships, and a greater empathy as we move through our personal worlds. That in the midst of all the crap, there is something else there that can be used for good in the future. Maybe it’s not even an issue of the glass being half-full or half-empty — instead, it’s an issue of “now, what are you going to fill your glass with?”
“The most important things in life are the connections you make with others.”—Tom Ford
While I am grateful to be attending ASH 2021 virtually this year, I do miss the experience of interacting with my fellow International Myeloma Foundation (IMF) Support Group Leaders (SGLs). I have fond memories of sharing meals with other SGLs and learning so much about their families, their professions, and the impact that myeloma has on their lives. I still remember my first ASH experience where I learned so much about the diverse histories of the amazing people with whom I attended. We were united by the common thread of myeloma.
I am particularly grateful to be attending this year’s ASH virtually because my dedicated dog is in “hospice” with worsening anorexia and plummeting weight loss. Despite her condition, she follows me to my office where I continue to learn more about the current and latest treatments for this unshakable disease. I remember her squeals when I came home from California from my stem cell transplant 11 years ago. I so appreciated her staying up with me when I had steroid-induced insomnia. In the middle of the night when I awoke with racing thoughts about my disease, my family, and my future, she was right there by my side. I will miss her dearly.
Don’t get me wrong, the amount of information I continue to learn is truly valuable and I look forward to sharing this knowledge with my local Support Group members. Most of our local meetings are highly informative and we learn about current therapies, new drugs, and their side effects. However, there is no real substitute for getting together in-person to communicate and share ideas and stories about our families and our treatments.
Listening to experts from across the globe means connecting with people who are committed to finding a cure and improving the lives of myeloma patients. We learn to appreciate their dedication to research and clinical trials. We anticipate hearing from them, year after year, as their research progresses from phase I to phase II studies. Even though we don’t know them personally, we start to develop a connection to them — somewhat like a favorite actor, musician, or athlete.
What a whirlwind of information it was this weekend! #ASH21 #IMFASH21
We learned about new and exciting studies related to monoclonal gammopathy of undetermined significance(MGUS) smoldering myeloma (particularly high-risk), and then active myeloma. I am so blessed to be able to participate in these presentations and gain this new level of insight into the myeloma world.
As a current high-risk myeloma patient with two young children, I started out as high-risk IGA MGUS and then developed high-risk smoldering myeloma (SMM). However, I continue to hope for a “magic wand” (as my son says) to cure this disease. Therefore, I am writing this blog from that perspective: (1) to encourage other multiple myeloma patients and caregivers, especially those with young children; (2) to provide uplifting information; and (3) to empower those with myeloma through these new educational resources.
As a previous high-risk IGA MGUS patient who had it for almost five years, the new studies out of Iceland with the iStopMM (Iceland Screens,Treats, or Prevents Multiple Myeloma) Study showed the importance of tracking MGUS. Depending on which type of MGUS you have, MGUS may have a greater tendency to turn into active disease. The iStopMM Study demonstrates the importance of tracking the disease so that doctors can monitor who may or may not progress into a different stage. Tracking the disease at an early stage allows myeloma patients and their medical team to monitor it carefully and decide when and if to move on to doing treatment. With early detection, a person can hope to avoid certain struggles and issues that they could face without early treatment.
If a patient moves from MGUS to smoldering myeloma, wow! What choices are coming down the road! Very exciting! As a patient who went from high-risk smoldering myeloma to active myeloma within 8 months, it is so encouraging to see the latest studies that show the benefits of treatment on high-risk SMM. It used to be that many high-risk SMM patients would use the “watch and wait” approach. While that still is a viable option (as there are considerations of starting therapies), it seems that there are some great outcomes when treating high-risk SMM patients. Some studies are showing promising results by using Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone (also known as KRd) and even KRd with a stem cell transplant. [Carfilzomib, Lenalidomide and Dexamethasone (KRd) as Induction Followed by HDT-ASCT, Consolidation with KRd and Maintenance with Rd. GEM-CESAR, paper 1829.]
If the patient then goes into active myeloma, again – I just have to say, wow! There are all sorts of options! There were a lot of presentations that added daratumumab to various drug combinations. From a non-medical standpoint, it seems that in most cases, Dara added to these various drug combinations increased the survival rates and deepened the responses. However, for some patient groups, Dara wasn’t always the “magic wand.” While Dara may still help that segment of myeloma patients, it was not as effective as it was in other groups. But overall, it was great to know about the effectiveness of the drug, and how Dara provides another available option in the treatment arsenal in this myeloma journey.
Another interesting topic point was the discussion on CAR T therapy and minimal residual disease (MRD) negativity. CAR T therapy may be another treatment option for myeloma patients that could beneficial. Again, looking at it from a lay person’s perspective, it seems that CAR T therapy has advanced and some of the side effects have gotten a bit better. The stats related to progression free survival (PFS) and overall survival is amazing! It is also exciting to see how CAR T affects MRD negativity. MRD negativity seems to be a key factor in a person’s success in their myeloma journey. It is interesting to see how CAR T continues to develop as part of the myeloma treatment plan.
One of the primary outcomes of attending ASH this weekend was gathering INFORMATION! While I may not completely understand the ins and outs of the therapies, drugs, side effects, charts, stats, and everything else (my head is still spinning!), ASH provides the latest information that allow for intelligent and meaningful conversations with the medical/treatment team.
Information allows myeloma patients to be empowered, be their own advocate, and partner with their healthcare team to help make the right decisions with current available information. By learning more about different treatment options, myeloma patients can ask questions like: Is the current treatment plan still the best approach? Are there novel advances that may work better at the current stage of myeloma? Is now the best time to hit myeloma harder? For all these questions, I have no answers. But, by learning about new treatment options and therapies, myeloma patients are empowered to talk to their doctors about options and to see if status quo is the way to go or if there are any changes that should be considered based on the new research.
I have learned so much this weekend! It was interesting to see the developments that are happening within the myeloma community. The treatments are advancing every day. Hopefully, one day, we will find that “magic wand.”
My son and what he would love to be his magic wand!
Today was another great day at ASH21, and antibodies (of course) took center stage in my choice of talks to attend.
Darzalex® (daratumumab), again, showed impressive results, this time in the ADROMENA trial for light-chain (AL) amyloidosis — a protein misfolding disease that can also occur in ~15% of multiple myeloma patients. These phase III trial results that were presented by Dr. Raymond Comenzo, MD, showed that the addition of Darzalex to Velcade/Cytoxin/dexamethasone (VCd) induction followed by Darzalex maintenance led to a 60% response rate compared to 20% in the VCd arm.
Most impressively, patients with renal or cardiac involvement showed improvements in organ function in the Dara-VCd arm. This talk was so moving to me because I lost a dear friend to AL amyloidosis years ago, which prompted me to switch my research focus to protein misfolding as a first step towards therapeutic development for protein misfolding diseases. I’m glad that there is now a good therapeutic option, at least for newly diagnosed AL amyloidosis patients.
Bispecific antibodies that targeted other sites besides BCMA have shown impressive results in preclinical and early clinical studies, offering options for patients who do not express BCMA on the surface of their myeloma cells.
Dr. Stefano Sammicheli, PhD, Director at Ichnos Sciences, presented early data on a first-in-class CD47/CD38 bispecific antibody innate cell modulator, ISB 1442. This antibody has two CD38+ epitopes that are distinct from daratumumab to bind myeloma cells as well as a CD47+ epitope to increase destruction of myeloma cells.
The preclinical data is impressive and first-in-human clinical trial enrollment is expected in mid-2022. Dr. Suzanne Trudel, MD presented data on the phase I clinical trial of another bispecific antibody, cevostamab — a FcRH5/CD3 bispecific antibody that facilitates the killing of myeloma cells. The safety profile is concerning, but a step-up dosing procedure seems to help, and it is a good option for relapsed, refractory patients who do not have an established treatment available for them.
Dr. Amrita Krishna, MD presented data on the MonumenTAL-1 Phase I study of talquetamab, a GCPRC5D/CD3 bispecific antibody that showed durable responses that deepened with time. A phase II expansion study is underway.
Additionally, Dr. Ajai Chari, MD presented results of the TRIMM-2 phase Ib study of talquetamab with daratumumab, which showed even deeper responses compared to monotherapy, with no increase in adverse effects. These data show that combination therapies with bispecific antibodies will be a promising future therapy option.
Dr. Sagar Lional, MD, FCAP gave an update on the phase 1/2 trial on iberdomide (IBER), a novel oral cereblon E3 ligase modulator (CelMoD), in combination with dexamethasone. While the overall response rate was low (26%) in this heavily pre-treated population, iberdomide is very well-tolerated with minimal side effects compared to other immunomodulators, likely because only the S isomer is administered so there are no off-target effects from the R enantiomer. The unique mode of action of CelMoDs warms this protein folder’s heart, and I expect to see future combination trials that will likely play an important role in new myeloma treatments.
In addition to novel antibody therapies, there were several interesting talks that focused on early precursors to myeloma and detection of myeloma in circulating plasma cells. In all of these talks, I was struck by how amazing the bone marrow environment can be.
Two trials that screened for MGUS indicated the importance of identifying patients at risk of progression to allow the best likelihood of treatment success. The first results on the IStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma) Study were presented. Incredibly, half of the population over 40 in Iceland was screened for MGUS, and the estimated prevalence of smoldering myeloma was 0.5%, making a case for early detection. Another IStopMM talk showed that the presence of MGUS did not increase the risk of COVID-19.
Additionally, several interesting talks from the lab of Dr. Irene Ghobrial, MD were presented today. Results from the PROMISE Study showed increased incidence of MGUS in high-risk populations. Molecular profiling of circulating multiple myeloma cells can predict disease aggressiveness, and liquid biopsies can be predictors of immune response in high-risk smoldering myeloma. The idea of blood biopsies to detect myeloma is very appealing – who wouldn’t be happy to have fewer bone marrow biopsies!
In one final talk from the lab of Dr. C. Ola Landgren, MD, PhD the immune microenvironment in the blood and bone marrow is normalized when there is an MRD-negative response to lenalidomide maintenance. How cool is it that your bone marrow can reboot and normalize after treatment? The bone marrow environment sure is complex but so incredibly amazing!
Even my kitty, Miss Lili, was impressed by all the results we saw today at ASH21. I am hopeful that all these fascinating studies will translate into new therapies for myeloma patients in the future!
Dec 11, 2021 – The day began at 3:30 a.m. PST for the privilege of being able to attend the International Myeloma Working Group (IMWG) meeting. The IMWG has over 250 myeloma specialists who meet twice a year. The agenda included a review of current projects and a discussion of possible proposals to specifically produce guidelines for myeloma treatment. For example, in 2021, guidelines were produced for redefining plasma cell leukemia as 5% circulating plasma cell, infection prevention (very timely during this pandemic), bone disease, and the role of mass spectrometry. Ongoing projects include the management of renal failure, CAR T, and smoldering multiple myeloma (SMM) guidelines.
Then it was off to “virtually” attend a number of first-day oral abstract presentations. The format of these 15-minute talks is for the primary investigator to present their slides for 10 minutes and allow 5 minutes for questions. The hybrid nature of this year’s ASH — where facilitators, presenters, and the audience is a blend of in-person and virtual— made this quite a challenge. This format worked better as the day went on but did cause some information to be missed, if you attended virtually. [On the other hand, it snowed in Atlanta 2 years ago and I missed some information while being there in-person.]
These are my highlights from today’s presentations: [Abstract#]
Iceland
There were at least 3 studies presented from the iStopMM project, which is in its 5th year. If you’re not familiar with this project and its potential importance, check out Dr. Brian G.M. Durie’s recent blog video.
One essential question asked was whether or not we should screen for monoclonal gammopathy of undetermined significance (MGUS). Other diseases offer early screening, resulting in the improvement of overall survival so why shouldn’t this be true for MGUS, a possible precursor to myeloma? Over 75,000 individuals were screened with nearly 4,000 MGUS patients found and after 3 years of follow-up some have become SMM and myeloma patients. [156]
While this is a long-term study, several interesting outcomes have already been determined: 1) SMM occurs in 0.5% in persons 40 years or older but according to today’s risk stratification, only 1/3 of these SMM patients are considered intermediate or high risk; [151] 2) There is no relationship between MGUS and the susceptibility of either getting COVID-19 or the severity of it. [154]
Bispecific Antibodies
There were several updates provided on bispecific antibodies with more to come on Sunday and Monday. The Bispecifics often use 1-2 “step-up” doses (start with lower amounts) to mitigate potential cytokine release syndrome (CRS). Today, abstracts provided results for:
1) Cevostamab (FcRH5 marker on the MM cell x CD3 on the T cell) given every 3 weeks to n=161 patients (pts) heavily pre-treated (including prior BCMA) resulted in ORR of 57% and mDOR of 11.5 mos for dosing 132-198mg via IV; [157]
2) Talquetamab (GPRC5D x CD3) given SubQ to N=55 pts resulted in ORR 67-70%; [158]
3) And when talquetamab is combined with dara N=21 showed an ORR 77-85% (no dara within prior 90 days); [161]
4) REGN5458 (BCMAxCD3) N=73 provided ORR = 75% at the combined 200-800mg dose levels. [160]
Other Studies
An update with a 2-year follow-up was provided for the Griffin study: [Dara]RVd -> SCT -> [D]RVd -> [D]R maintenance (2 yr). Dara arm results in superior outcomes after 2-year follow-up: MRD- (10-5) 64% vs 30%, CR 82% vs 61%, and MRD- >12 mos durability 44% vs 13%. [79]
Iberdomide (a CELMod) + dex demonstrates efficacy in triple-refractory patients, including those 100% refractory to IMIDs, ORR 26% N=26 and pts with previous BCMA, ORR 25% N=24. [162]
The PROMISE study examines potentially high-risk individuals, specifically Black/AA (N=2439) and those with first degree relative dx with hema malignancy or precursor to MM (N=3866). MGUS screening via both SPEP (6%) and Mass Spec (13%) confirmed both higher rates and increased sensitivity with Mass Spec. [153]
That’s it for tonight. While my first meeting tomorrow isn’t until 6:30 a.m. PST, one benefit of a virtual ASH is that many sessions are recorded and available for replay (just in case I oversleep).
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