Timing treatment for smoldering myeloma: is earlier better?

ABSTRACT

Introduction: In 2014, the International Myeloma Working Group determined that patients with ultra-high-risk smoldering multiple myeloma (SMM) should be considered for treatment as per patients with symptomatic multiple myeloma (MM), despite not having CRAB (hyperCalcemia, Renal insufficiency, Anemia, Bone disease) symptoms. Current research is elucidating whether patients with high-risk, and even intermediate-risk, SMM could benefit from early therapeutic strategies aimed at delaying progression to active MM and prolonging survival.

Areas covered: The authors conducted a systematic literature search using PubMed to identify a series of patients with SMM in which prognostic and predictive factors for progression were investigated, plus the main clinical trials in SMM. Additionally, a search of active clinical trials in SMM was conducted at ClinicalTrials.gov.

Expert opinion: Patients with high-risk SMM can benefit from active treatment strategies, which may prolong survival and, perhaps, provide a possible path to cure. Enabled by the limited toxicity of new drugs investigated in MM, this approach, together with consolidation with autologous transplantation, is under investigation by American and European groups. In patients with high-risk SMM who are not candidates for transplantation, combinations of oral drugs may prolong time to progression. In the near future, these approaches may be endorsed by results of ongoing clinical trials.

KEYWORDS:

• Active treatment
• cure
• early therapy
• high-risk
• smoldering multiple myeloma

Article highlights

• The main risk-stratification models for patients with smoldering multiple myeloma (SMM) are those developed by the Mayo Clinic and the Spanish Myeloma Group (GEM/Pethema). A new model developed by the Mayo Clinic, which combines the risk factors of M-protein ≥2 g/dL, serum free light chain (sFLC) ratio >20, and bone marrow plasma cell percentage (BMPC%) ≥20 is currently being validated.

• Patients with ultra-high-risk SMM (BMPC% ≥60, sFLC ratio >100, or >1 focal lesion on magnetic resonance imaging) should be treated per patients with active multiple myeloma (MM), based on the recommendations of the International Myeloma Working Group.

• Old drugs, previous to bortezomib and lenalidomide, used for the treatment of patients with MM do not provide benefit in patients with SMM.

• Recent evidence has shown that the use of lenalidomide plus dexamethasone can delay progression to symptomatic MM and increase survival in patients with high-risk SMM.

• In younger patients, current clinical trials are aiming to achieve very deep responses, which result in delayed progression and longer survival. Some of these strategies are raising the possibility of finding a ‘path to cure’ in these patients.

• In older patients, combinations of drugs – preferably oral – are being investigated with the aim of prolonging survival while demonstrating a good safety profile.

Declaration of interest

JA Hernandez has served on advisory boards for Janssen Celgene, Amgen, and Takeda and has received honoraria from Amgen and Takeda. JJ Lahuerta has acted in a consulting or advisory role for Janssen-Cilag, Celgene, Takeda, and Amgen. J Martinez-López has acted in a consulting or advisory role for Novartis, Celgene, Janssen, and Bristol-Myers Squibb and on a speakers’ bureau for Novartis, Celgene, Janssen and Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.