Attending the 63rd American Society of Hematology (ASH) meeting for the first time was an illuminating experience! I feel quite privileged to be a part of the International Myeloma Foundation (IMF) team and to have this educational opportunity. This was an amazing experience and I’m so grateful! Thank you, IMF and my fellow team members!
In my Pre-ASH blog, I organized the SMM abstracts into five (5) categories. To wrap things up, it makes sense to provide highlights from those categories. In some, MGUS research had insightful findings, so those are included as well. Hold on tight — here we go!
- Prevalence/demographics: The iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) project provides the most compelling data in this category, as they have screened about half of the Icelandic population (40 years and older). They found that 4.9% are monoclonal gammopathy of undetermined significance (MGUS) and .5% are smoldering multiple myeloma (SMM). These numbers suggest that both precursor conditions are more prevalent than previously known. This is, perhaps, not surprising since many MGUS and SMM diagnoses are incidental. The caveat to this data is that Iceland is not very diverse.
The PROMISE study focuses on a Black/African American sample as well as those with a first-degree relative who has a hematologic disorder. They found that the prevalence of MGUS was 10%, higher than expected. This study is ongoing as well, so more results will be forthcoming.
- Risk identification/disease progression: Again, iStopMM has interesting findings related to disease progression, as they have followed the screened MGUS individuals (n=3487) for three (3) years. Using a randomized control trial, MGUS screened individuals were placed in one of three arms: (1) not contacted about MGUS (n=1164), (2) followed based on current MGUS guidelines (n=1159), (3) followed with more intensive diagnostics and monitoring (n=1164).
This table shows those who progressed to another diagnosis from each group:
|Arm 1(n=1164)||Arm 2 (n=1159)||Arm 3 (n=1164)|
|Smoldering Myeloma||0||56 (4.8%)||82 (7.0%)|
|Multiple Myeloma||4 (.3%)||12 (1.0%)||16 (1.4%)|
|Other lymphoproliferative disorder||5 (.4%)||24 (2.1%)||35 (3.0%)|
|Total:||9 (.7%)||92 (7.9%)||133 (11.4%)|
- Treatments/preventing progression: Two strategies currently exist in treating SMM: one is treat to delay progression and the other is treat to cure. These trials are primarily for those with high-risk SMM, although one preliminary result was also reported among those with MGUS and low-risk SMM. MGUS and LRSMM patients are taking daratumumab, and most have demonstrated a response of some degree at this point in time. Longer follow-up is needed to provide a complete picture. The other result was that Grade 3 toxicities occurred in only 5 of 41 patients, while other minor side-effects occurred among more patients.
Findings in the high-risk area are also preliminary, but promising, with longer follow up needed. The following are being studied: (a) the 3-drug combo of ixazomib, lenalidomide, and dexamethasone designed to delay progression, and (b) the combination of KYPROLIS®(carfilzomib), REVLIMID® (lenalidomide), and dexamethasone (KRd) plus stem cell transplant designed to cure.
- Disease mechanisms: Frankly, I struggled to understand much of the work in this area. But from my perspective, it seems like various markers are being investigated which can help with earlier disease identification, and I also heard remarks about further stratifying SMM patients into those who may need less frequent follow-up, those who may need closer observation, and those who should probably start treatment. Investigators are looking at things like genomic profiles, mutations, Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) activity, and clonal level markers, among other things. Again, to me this was pretty complex stuff, and I hope to learn more about some of these things in the future. The possibilities do seem quite exciting, however, even to this non-biologist. (Does anyone have a Disease Biology for Dummies book I could borrow?)
- COVID-19/vaccine-related information: The iStopMM project again reveals helpful information, as screened MGUS patients had similar rates of SARS-CoV-2 susceptibility and COVID-19 severity, compared to the general public. Regarding SMM patients, one study examining MM patients undergoing treatment also included a small sample of SMM patients in the “no-active-treatment” group. Since the study was focused on treatments, I didn’t see specific statistics regarding the no-active-treatment group, but the figure showed what looked like a slightly depressed response compared to the healthy control group (with no previous COVID-19), especially post dose 1 and within 10 days of receiving dose 2.
To all who have read my blogs, thank you for your interest and attention. I hope that I’ve been able to provide valuable information and insights. I also wish you the very best, in this season of hope.
Jessie Daw, on Twitter @Daw6Jessie