- Smoldering multiple myeloma (SMM)
is an asymptomatic disorder which includes patients at low, intermediate
or high risk of progression to symptomatic multiple myeloma.
- The risk of progression is not
uniform and all newly diagnosed SMM patients should be classified
according to their levels of risks. There are several useful markers that
identify patients who are susceptible to increased risk of progression.
- SMM patients at high-risk of
progression to the symptomatic stage should be identified because these
patients require close follow-up and inclusion in clinical trials if
- A recent study has compared the
standard care for SMM (observation) with early treatment with lenalidomide
Smoldering multiple myeloma (SMM) is an asymptomatic form of multiple myeloma where the patients have features similar to multiple myeloma like high levels of plasma cells and M protein but without bone diseases. The standard of care for SMM patients is observation without administration of medications until symptoms appear. However, a recent study that has compared observation with treatment with lenalidomide and dexamethasone has revealed that early treatment may benefit high-risk patients
Dr. Maria-Victoria Mateos et
conducted an open-label randomized controlled phase 3 study at around 19
different centres in Spain and three centres in Portugal. High-risk SMM
patients who were above 18 years old were assigned randomly through a
computerized random number generator to be observed without receiving
medications or to receive lenalidomide plus dexamethasone treatment.
‘Compared to Observation, Early treatment with Lenalidomide and Dexamethasone lowered disease progression in High-risk Smoldering Multiple myeloma patients.’
Patients enrolled in the treatment group received nine 4-week
induction cycles, i.e. in each cycle, they received 25 mg of lenalidomide per
day on days 1-21 and 20 mg of dexamethasone per day on days 1-4 and days 12-15.
This was then followed by maintenance therapy for 2 years (10 mg of
lenalidomide per day on days 1-21 per each 28-day cycle).
The authors found that the progression to multiple myeloma
occurred among 39% of patients in the treatment group compared to 86% of patients who belonged to the observation group. Eighteen percent people in the treatment group and 36% patients in the observation group died within the cutoff date of the study. Infection, neutropenia (low white blood cell count), asthenia and skin rash were the most frequently reported grade three adverse events in patients who were given lenalidomide and dexamethasone. There weren't any grade four adverse effects noted, but one patient in the treatment group died from a respiratory infection during the treatment. Second primary cancers were more frequent in patients who belonged to the treatment group (10%) as compared to those of the observation group (2%).
This study is possibly the first randomized trial where early
treatment has been used in selected high-risk SMM patients. This study has made
it evident that early treatment with lenalidomide plus dexamethasone reduced
the progression time for high-risk SMM patients to multiple myeloma as compared
to observation. Positive results from this ongoing study might support early
treatment with lenalidomide plus dexamethasone for high-risk multiple myeloma
patients in the near future. Also, novel therapeutic approaches would determine
whether early treatment with newer medications for high-risk SMM patients could
prevent myeloma-related symptoms from developing.
- Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up a randomised, controlled, phase 3 trial - (http://www.ncbi.nlm.nih.gov/pubmed/27402145)
- Smoldering Multiple Myeloma: When to Observe and When to Treat? - (http://meetinglibrary.asco.org/content/11500484-156)
- QUIREDEX: Revlimid (Lenalidomide) and Dexamethasone (ReDex) Treatment Versus Observation in Patients With Smoldering Multiple Myeloma With High Risk of Progression (QUIREDEX) - (https:clinicaltrials.gov/ct2/show/NCT00480363)