ASH 2022 | Should we treat smoldering myeloma?

Smoldering multiple myeloma is not a malignancy. Smoldering multiple myeloma is a statistical risk assessment of developing multiple myeloma in the future. And importantly, there are multiple clinical trials trying to address this. However, outside of a clinical trial, I strongly advise against making a decision at one office visit about whether a patient should or should not be treated.

Scrutiny of prior trials that have randomized patients with high-risk smoldering multiple myeloma show there is poor agreement among trials as to what constitutes smoldering multiple myeloma. The first trial that showed a survival advantage was severely flawed because patients were randomized without high-end imaging such as an MRI or a PET scan to rule out active bone lesions. In addition, patients on placebo that ended up progressing with a rise in their M protein did not come off trial because they simply didn’t have CRAB criteria as yet. Finally, there was no control for patients who were on placebo when they progressed. The patients in the treatment arm received lenalidomide. Most patients were not able to access lenalidomide since it was not approved for the treatment of their multiple myeloma. So one has to be cautious in interpreting these results.

The second trial, done by ECOG, did not include a significant component of high-risk patients. In fact, in the placebo arm, only one third of patients developed multiple myeloma in three years. So rephrasing that, two-thirds of patients would not develop multiple myeloma in three years, and in my opinion, these patients should not be candidates for treatment. So if not enrolling patients in a clinical trial, I would strongly advise clinicians in the community to follow patients closely for a few months to see if the M protein velocity suggest rapid evolution into multiple myeloma.

Finally, I want to note that a recent publication has indicated that a light chain ratio greater than 100 is not a myeloma defining event. Only when patients had a proteinuria did they have a significant risk of myeloma. But even then, the median time to myeloma was over three years. A light chain over 100 without proteinuria, median time to myeloma was seven years. So please use caution before you reflexively consider therapeutic intervention for a completely asymptomatic patient with smoldering myeloma.