ASH wrapped up today (Tuesday) with the Late Breaking Abstracts session, but yesterday (Monday) had a lot of myeloma-related sessions, both oral and poster presentations. It’s been quite a weekend! I’ve categorized and summarized more research related to smoldering myeloma (SMM), and hope that you find it useful.
Risk Factors and Diagnosis:
The iStopMM study investigated various risk factors for SMM compared to monoclonal gammopathy of undetermined significance (MGUS) and controls (Sigrun Thornsteinsdottir, MD, PhD, Risk Factors of Smoldering Multiple Myeloma: Results from the Screened iStopMM Study). Interestingly, they found that while lifestyle factors like body mass index (BMI), smoking, alcohol consumption, and prior autoimmune diseases or chronic infections weren’t significantly associated with increased odds of SMM, specific blood assessments revealed marked differences between MGUS and SMM. These included immunoparesis, abnormal FLC ratio, IgA isotype, and increasing M-protein levels. These findings suggest that while demographic and behavioral factors might not distinguish SMM from MGUS, blood assessments linked to the plasma cell clone are indicative of the transition to SMM.
Novel Therapies and Intervention Studies:
In my Saturday, December 9th blog, I shared some clinical study updates provided on Day 1 of ASH. Some additional clinical trial research was presented. Promising therapeutic avenues have emerged, such as linvoseltamab and the combination treatment D-RVD. Linvoseltamab, a BCMA x CD3 bispecific antibody, demonstrated encouraging results in inducing deep and durable responses in relapsed/refractory multiple myeloma (RRMM). Studies using linvoseltamab, like LINKER-SMM1, aim to evaluate its safety and clinical activity in early intervention for high-risk SMM patients (Paula Rodriguez Otero, MD, PhD, Trial in Progress: A Phase 2 Study of Linvoseltamab for the Treatment of High-Risk Smoldering Multiple Myeloma (LINKER-SMM1). Similarly, investigations into D-RVD’s impact on high-risk SMM showcase positive outcomes with early MRD negativity and manageable safety profiles (i.e., no patients dropped out due to toxicities). These ongoing trials are crucial in understanding the efficacy, safety, and potential benefits of early intervention in high-risk SMM. (Omar Nadeem, MD, Phase II Trial of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma).
Prognostic Markers and Disease Progression:
Studies have delved into prognostic markers and disease progression in SMM. Detecting circulating tumor cells (CTCs) using next-generation flow cytometry (NGF) has shown potential in predicting progression from SMM to active multiple myeloma (MM). The presence of CTCs is associated with a trend towards an increased risk of progression from SMM to active MM. However, longer follow-ups are essential to fully understand the role of CTCs as a prognostic biomarker and their additive value in risk stratification tools (Efstathios Kastritis, MD, Circulating Tumor Cells By Next Generation Flow Cytometry May be a New Prognostic Biomarkers Among Patients with Asymptomatic Monoclonal Gammopathies). Additionally, genomic profiling has provided insights into SMM’s heterogeneity, uncovering potential therapeutic targets and aiding in monitoring disease transformation (Jean-Baptiste Alberge, PhD, Genome Sequencing to Discover Drivers of Clonal Expansion in Smoldering Multiple Myeloma).
Further research comparing SMM patients who progressed to active MM with those newly diagnosed showed some interesting findings. Patients developing active MM after SMM clinic monitoring had lower disease burden and fewer harmful bone issues. They also had better survival rates. This might be because of effective SMM monitoring leading to less severe disease when treatment begins, or it could relate to different treatment approaches between these groups. Additionally, some patients with slower-growing conditions might be diagnosed incidentally during their SMM phase due to extended periods of precursor conditions. (Yael Cohen, MD, Smoldering Multiple Myeloma Progressing to Active Multiple Myeloma Vs De-Novo Active Multiple Myeloma – a Comparison of Disease Characteristics, Organ Involvement and Outcomes in a Real-Life Multicenter Retrospective Cohort Study). These studies highlight the importance of identifying biomarkers for early intervention and understanding disease evolution in SMM.
Patient Preferences and Lifestyle Interventions:
Understanding patient preferences and potential lifestyle interventions is vital. Studies exploring patient preferences for intervention in individuals with MGUS and SMM reveal diverse risk tolerances and varying priorities among patients. Some prioritize MM risk reduction over side effects and cost, suggesting a need for a range of interventions that align with patient preferences beyond the current “watchful waiting” or “active surveillance” paradigm (Catherine Marinac, PhD, Understanding Patient Preferences for Intervention in Individuals with Precursor Multiple Myeloma: The Preference Study). Additionally, investigations into a whole food plant-based diet show potential in altering disease trajectory by improving metabolic profiles, microbiome diversity, and immune subsets. These findings suggest the importance of considering patient preferences and exploring lifestyle interventions as potential adjuncts to existing approaches (Urvi Shah, MD, A Whole Foods Plant-Based Weight Loss Intervention Improves Quality of Life, Metabolic, Microbiome and Immune Profile in MGUS/SMM As Well As Progression Trajectory in a Subset – the Nutrivention Trial).
External Influences and Associations:
Exploration into external influences, like the impact of SARS-CoV-2 infection, suggests intriguing associations. Studies indicate no direct evidence linking SARS-CoV-2 infection to the progression of MGUS to MM. However, observations note that unvaccinated individuals with higher baseline M protein concentrations experienced a significant increase in M protein after SARS-CoV-2 infection. This implies a potential influence of baseline risks and vaccination status on disease progression, signaling the need for further investigation into external factors affecting disease trajectories. (Robert Palmason, MD, Sars-Cov-2 Infection Does Not Lead to Progression of Monoclonal Gammopathy of Undetermined Significance: Results from the Population-Based iStopMM Screening Study).
In conclusion, these diverse studies collectively underscore the multifaceted nature of SMM. They highlight the necessity for tailored approaches, identification of prognostic markers, and consideration of patient preferences alongside potential external influences for effective management and possible intervention strategies.
Thank you for reading, and I hope you have found this information valuable. Stay informed, stay proactive, and engage with your healthcare team so you can navigate your journey with confidence.
— Jessie Daw
@Daw6Jessie