Towards ASH 2020: Highlights on smoldering multiple myeloma

Since the last American Society of Hematology (ASH) meeting, smoldering multiple myeloma (SMM) has continued to draw attention in the field of multiple myeloma (MM). Recent discussions focused on two main topics: identifying the patients who could benefit the most from early treatment and how they should be treated.

To prepare for the 62^nd ASH Annual Meeting & Exposition, which will be held between December 5–8, 2020, we have summarized the recent advances in SMM covered on the Multiple Myeloma Hub from last year, and how we plan to cover this topic at the 2020 meeting.

How to accurately identify candidates for early intervention

We were pleased to speak to the Multiple Myeloma Hub Steering Committee member, Irene Ghobrial, Dana-Farber Cancer Institute, Boston, US, about the recent advances in our understanding of myeloma progression during the 6^th Controversies in Multiple Myeloma (COMy) World Congress. Irene Ghobrial discussed the need for criteria to define patients who would progress to active MM in their lifetime and benefit from early intervention. Listen below to her detailed explanation of the clinical markers to help experts define patients with high-risk SMM.

In 2019, the International Myeloma Working Group (IMWG) revised its diagnostic criteria for high-risk SMM as a “2/20/20” model, which corresponds to:

• Serum M protein > 2 g/dL
• Involved to uninvolved serum free light-chain ratio > 20
• Bone marrow plasma cell infiltration > 20%

This risk stratification model is considered a useful tool in identifying patients with SMM who have a > 50% probability of progressing to MM in 2 years. The presence of a chromosomal abnormality may be included as an additional risk factor to these three parameters. A more detailed discussion on the IMWG 2/20/20 risk stratification model can be found here.

During the 2020 ASH meeting, we will learn about several initiatives attempting to identify more accurately patients who are at a higher risk of progression to MM amongst those who could be safely followed with a ‘watch and wait’ approach. Upcoming abstracts include:

• The iMMunocell study by Rosalinda Termini, investigating longitudinal immunogenomic profiling of tumor and immune cells
• A comprehensive genomic analysis that could help in identifying low-risk SMM, by Anil Aktas-Samur
• The use of low-dose whole-body CT to detect bone lesions at an early stage in progression to MM, by Maria Gavriatopoulou
• The impact of CD56 expression on disease progression by Laura Notarfranchi
• The results of a prospective observational study investigating a variety of genomic, immunological, and clinical parameters that may be predictors of progression, by Elisabet Manasanch

How to treat SMM

The debate on whether SMM should be treated early, when it is a less complex disease, is still ongoing.

Watch our interview from the 61^st ASH meeting with Irene Ghobrial on treating SMM. Irene Ghobrial argues that patients with SMM should be treated once there is an agreement on defined selection criteria, and she discusses SMM therapeutic options such as lenalidomide-based therapies and daratumumab for low-risk SMM.

In the following interview from ASH 2019, Mark Bustoros, Dana-Farber Cancer Institute, Boston, US, presents the results from a phase II trial of ixazomib, lenalidomide, and dexamethasone in treating high-risk SMM. This combination is associated with promising results with a favorable safety profile.

During the eighth annual meeting of the Society of Hematologic Oncology (SOHO), Angela Dispenzieri, Mayo Clinic, Rochester, US, and Multiple Myeloma Hub Co-Chair, María-Victoria Mateos, University Hospital of Salamanca, Salamanca, ES, debated whether SMM should be treated. María-Victoria Mateos has argued that patients should be treated from two main perspectives: (1) to prevent the development of MM, and (2) to cure the disease before progression to MM. Several agents, including elotuzumab, ixazomib, carfilzomib, isatuximab, and daratumumab, demonstrated positive results for prevention. In a curative approach, carfilzomib-based therapies were associated with promising results based on the phase II GEM-CESAR trial data. On the other hand, Angela Dispenzieri argued that SMM should not be treated yet, as most cases identified by the available tools today would not progress to MM. She advocates for a larger and broader validation of the described SMM risk stratification models. Find out more on this thorough discussion here.

At the moment, there are several ongoing clinical trials, but the GEM-CESAR study presented last year at ASH leads the field of curative approaches being evaluated for patients with SMM. Review the preliminary key results in this interview with María-Victoria Mateos:

New treatment approaches for high-risk SMM will be also be discussed this year. Dickran Kazandjian and Elizabeth Hill, of the National Cancer Institute, Bethesda, US, will be presenting the results of a phase II study evaluating carfilzomib, lenalidomide, and dexamethasone (KRd) followed by lenalidomide maintenance and the value of ¹⁸f-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) for the evaluation of the depth of response achieved with it. Additionally, Shaji Kumar will present preliminary safety data from phase II ASCENT trial investigating induction (carfilzomib, lenalidomide, daratumumab, dexamethasone), consolidation (daratumumab, dexamethasone), and maintenance (lenalidomide, daratumumab) approaches in patients with high-risk SMM.

The MM Hub will be providing live coverage, summary articles on key sessions, and interviews with leaders in the myeloma field during the 62^nd ASH Annual Meeting & Exposition. Stay tuned!