By Jerry Walton
Virginia Beach, VA

There was lots of good information in Dr. Jesus San-Miguel’s lecture on multiple myeloma (“MM: A model for scientific and clinical progress”). Myeloma resistance to treatment was one issue.

Myeloma cells that persist after treatment are a reservoir for clonal evolution and disease recurrence. The cells can evolve to different forms, resistant to prior treatments. Myeloma cells and their genetic aspects are not sufficient targets. We also need to target the microenvironment around and interacting with the myeloma cell.

Better quality of response to treatment (e.g., complete response/CR) promotes longer survival.

However, the current definition of CR is suboptimal. We need to add measures outside of the bone marrow, such as PET/CT scans, and define a CR that includes it. The emerging Minimum Residual Disease (MRD) via the Black Swan Research Initiative is getting us closer to a better CR measure.

There is a wide range of smoldering multiple myeloma (SMM) disease, due to the great heterogeneity/difference in myeloma cells. In one clinical trial, high risk SMM had a median progression to symptomatic MM of 23 months. Therefore, treatment is proposed for patients with greater than one focal lesion, greater than 60% of plasma cells in the bone marrow, or a free light chain ratio > 100. They should be considered as early myeloma patients requiring treatment.

Regarding early versus late transplant, a large study showed that early stem cell transplant (SCT) is better than late SCT. Progression Fee Survival (PFS) was 51 months for early SCT versus 32 months for late. Four-year overall survival was 85% for early and 76% for late. Three randomized trials comparing early and late SCT are ongoing.  Consolidation with 2 to 3 courses of combination therapy is done to reduce residual disease after the High Dose Therapy/SCT.

The Italian group has shown the value of Velcade (Bortezomib),Thalidomide (Thalomid) and Dexamethasone consolidation therapy, improving both CR and PFS.

Six trials have compared tandem autologous SCT (ASCT) with ASCT followed by reduced intensity allogenic (donor) transplant. The allogenic option was better in only two of the six, and is therefore not recommended in newly diagnosed patients. It should, however, be reexamine in trials for high risk patients in the context of emerging novel therapies.

Dr. San-Miguel’s presentation covered many more myeloma topics, providing an excellent foundation prior to numerous more specific myeloma oral and poster presentations.

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