high-risk multiple myeloma | The IMF at ASH 2024

Smoldering Myeloma at ASH 2024: What We’ve Learned So Far

Dec 9, 2024 | Jessie Daw

The first two days of the 66^th American Society of Hematology (ASH) Annual Meeting—Friday’s Satellite Symposium and Saturday’s research presentations—offered limited content specifically focused on smoldering myeloma (SMM). However, a few key discussions stood out, providing insights into treatment strategies, disease progression mechanisms, and the psychological impact of living with precursor conditions. These set the stage for additional abstracts on SMM during the rest of the conference.

Understanding Disease Progression: From MGUS to Myeloma

A presentation by Dr. Michaela Liedtke, MD, examined the mechanisms driving the progression of monoclonal gammopathy of undetermined significance (MGUS) to active myeloma. While the talk focused on MGUS, the findings are also relevant for SMM, which serves as an intermediate stage.

Dr. Liedtke categorized progression mechanisms into three main areas:

Clone Intrinsic Factors: These include the type and level of the M-protein, abnormal light chain ratios, and specific genetic mutations.
Clone-Host Interactions: The interplay between cancerous cells and the patient’s immune system or bone marrow microenvironment is critical in disease evolution.
Host Factors: Patient-specific factors, like age and obesity, also influence disease progression.

These insights reinforce the importance of understanding individual risk profiles in managing precursor conditions like MGUS and SMM. Questions I have as someone with SMM include how can we significantly change our immune system function and/or the bone marrow microenvironment? Also, while I cannot control my age, I do have some measure of control over my body mass and fitness.

Treatment Decisions for Smoldering Myeloma

The transition from smoldering myeloma (SMM) to active myeloma is complex, and decisions about treatment are critical. In one of Friday’s Satellite Symposiums, Dr. Shaji Kumar, MD, presented on “Newly Diagnosed Multiple Myeloma: Many Choices and More Questions,” and this content has some relevance for those with SMM. As a reminder, the standard of care for low and intermediate-risk SMM is active surveillance, while for high-risk, it is either active surveillance or possible treatment, preferably within a clinical trial.

One of the key messages is that the first treatment can set the stage for long-term outcomes. Indeed, the goals of initial treatment were highlighted.

We want to use the very best treatment first, as we don’t want any subclones that remain and develop into treatment-resistant clones down the road. Dr. Kumar highlighted obtaining the deepest response possible, and I’ve heard other specialists emphasize that making the initial therapy the best possible choice can influence overall survival and quality of life.
Additionally, care must be tailored to each individual. Factors like genetic markers, disease aggressiveness, and a patient’s overall health (including frailty) play crucial roles in developing a treatment plan. Frailty in particular was highlighted as a major determinant of survival and should inform both treatment intensity and supportive care measures.

For those with SMM, this information is crucial, especially when deciding between active surveillance/watchful waiting, starting treatment, or participating in clinical trials. For me personally, I’ve decided to wait as long as possible to start treatment (I have three high-risk cytogenetic features), using the time instead to get in the best shape possible while eating the best foods possible.

The Psychological Toll of Precursor Conditions

Living with a precursor condition such as MGUS or SMM is not just a physical challenge—it’s a mental one, too. Interestingly, while some specialists have noted that their SMM patients experience higher levels of anxiety than those with active myeloma, studies on this topic have produced conflicting results.

At last year’s ASH, the iSTOPMM study reported minimal psychological impact associated with being diagnosed with a precursor condition. However, a UK-based study by Dr. Sandra Quinn, PhD, and colleagues presented at this year’s ASH found the opposite. Using both quantitative surveys and qualitative analysis, the study revealed that both MGUS and SMM patients experience reduced health-related quality of life (HRQoL) compared to the general population.
Key findings included:

MGUS patients reported worse outcomes than SMM patients in areas like anxiety, depression, fatigue, and sleep disruption.
Qualitative data highlighted themes such as:
- Living with the Unknown: The uncertainty of disease progression weighs heavily on patients.
- Prevention as Cure: Many patients feel they are constantly searching for ways to prevent disease progression.
- Remediation Through Treatment: Treatment is often seen as the only way to restore normalcy.
- Needless Suffering: Some patients feel trapped by the lack of clear guidelines for managing precursor conditions.
This underscores the need for psychosocial support alongside clinical care to help patients navigate the emotional challenges of living with these conditions. Personally, I experienced significant anxiety in the first few years after my diagnosis. I’m more accepting of this now, and in a way, I look at this diagnosis as a gift as I’ve been given the opportunity to re-evaluate my life and how I’m living it. I think I needed some critical incident to make this happen, and I appreciate the changes I’ve made.

Final Thoughts

While the first two days of ASH 2024 offered limited SMM-specific content, these highlights provide valuable perspectives for patients and providers alike. The conference schedule suggests that Sunday, and especially Monday, will feature more in-depth discussions on smoldering myeloma. Stay tuned for additional updates as the conversation around SMM continues to evolve.

@Daw6Jessie

New Words: I Feel Smarter Already!

Dec 7, 2024 | Barbara Davis

The first day is kind of a beginner’s day, with a number of Continuing Medical Education (CME) courses/presentations. I went to two: The first was Championing the Care of Relapsed/Refractory Multiple Myeloma: Practical Strategies to Integrate Bispecific Antibodies, and it was presented by Drs. Ajai Chari and Amitra Krishnan. Here are some of its key points:

Heavily pretreated relapsed/refractory (R/R) patients will continue to fail more and more drugs
In the HORIZON study, there were three bispecific antibodies: linvoseltamab, Tecvayli (teclistamab), and Talvey (talquetamab) used, each in a different arm of the study. Patients were heavily pretreated relapsed-treated MM patients, yet, they still each had an overall response rate (ORR) of over 60%
Oral and skin toxicities were higher with talquetamab, but the infection rate was lower. Both doctors agreed that patients must be warned about skin problems. Also dysgeusia (my new favorite word, means abnormal taste), weight loss, and (rarely) cerebellar ataxia (poor muscle coordination).
They discussed how to choose between CAR T-cell therapy and bispecific antibodiess? Timing is very important. Dr. Chari said to consider the time from “brain to vein,” meaning the time when the doctor first thinks about putting a patient into the CAR T list to when the patient’s T cells are reinfused is long. So, the question is can the patient last long enough, or is their disease rapidly progressing? In the latter case, a bispecific antibody would be the better choice.
There’s still much learning to be done about sequencing these new therapies. “More questions than answers,” said Dr. Chari.
Management of key toxicities is extremely important. Clinicians must treat for cytokine release symptoms (CRS) as the first symptom. Also, infection management must be done at first onset, often giving IVIG as soon as treatment is started.
“Bispecific antibodies will become as routine as Darazalex (daratumumab) now,” said Dr. Krishnan.
Bispecifics and other MM drug combos are currently off-label.
Phew! It was an interesting discussion, and I was pleased that I understood so much. The next session was a bit harder, but I’ll tackle that report tomorrow. It was about Optimizing CD38 antibody-based triplet regimens for early relapse MM. For my fellow patients, you probably know that early relapse is a signal that your myeloma is showing itself to be high- risk. That sounds scary; and it is scary, but I was also impressed that so much energy is being put into drug development and clinical trials to learn how to successfully treat the high-risk patient.

Looking for the Light at ASH!

Dec 2, 2024 | Terry Glassman

I was diagnosed with Multiple Myeloma/Plasma Cell Leukemia (MM/PCL) in November 2022. For a solid 2 months, I was a bit paralyzed by my diagnosis, and the induction road was rocky. Yet, eventually, things smoothed out and I started my quest to learn all I could learn and then started reaching out to help others. As an RN, my learning curve was a bit shorter than most, but there is SO much to learn about MM! I’d say at this point, I have a decent understanding of the disease, but there is always more to learn and thankfully new information/treatments/medications keep coming. I am so honored and excited to attend ASH with the IMF as it is the ultimate meeting in Hematology/Oncology and, being the nerd I am, I can’t wait to learn and share!

My goal as an IMF Voice at ASH is to learn as much as possible and share that knowledge with all my fellow MM Patients. As a high-risk patient myself, I’ll put an emphasis on presentations that focus on the high-risk population. I am also very interested in how MRD (Minimal Residual Disease) testing may affect or change the landscape of MM treatment and research studies. I have experience in research, albeit as a cardiac research nurse, so the potential of MRD Negativity as an endpoint to facilitate research intrigues me. Another area of personal interest is decreasing the dose of dexamethasone. I’m not sure if this topic, will be discussed but if it is…I’ll be there. I was one of those people who took 40mg of Dex for 5 days; and yes, it made its mark in a very negative manner! And finally, I look forward to what’s new and on the horizon.

I have found that even when you think people understand the MM Journey, they don’t. I’m sure we all have people who we have explained MM to only to have them say a few months later “So, when are you finished with chemo”? If my attendance at ASH can help others better understand MM, while also helping to keep my fellow MM patients updated, then it’s a huge win/win! The biggest fear I had when I was diagnosed was that I would lose my ability to help people. My involvement with the IMF has given me the ability to regain what I cherish most in life…helping others! So again, I thank the IMF for this amazing opportunity to learn from those who work so diligently for us all! In the words of my MM Specialist: “the longer I keep you alive, the longer I can keep you alive.” I am sure that sentiment is in the minds of all these amazing scientists, and I look forward to learning from them all! SCIENCE, IT’S LIKE MAGIC, BUT REAL!

~Terry Glassman~
@TerryGlassman