High-risk smoldering myeloma can progress to symptomatic multiple myeloma within five years after diagnosis. The risk of progression is approximately 75%, and it can be decreased by lenalidomide treatment. According to a phase II nonrandomized controlled trial, novel triplet regimens with Carfilzomib, Lenalidomide and Dexamethasone (KRd) followed by lenalidomide maintenance therapy shows better results than treatment with lenalidomide alone. Earlier disease may be also more treatment-sensitive.
This trial enrolled 54 patients with high-risk smoldering myeloma from the National Institutes of Health Clinical Centre, a highly specialized tertiary cancer centre, from May 2012, to July 2020. Patients received eight 4-week cycles of intravenous carfilzomib 36 mg/m2 (first 2 doses, 20 mg/m2), dexamethasone (20 mg, cycles 1-4; 10 mg, cycles 5-8 twice weekly), and lenalidomide 25 mg (days 1-21) followed by twenty-four 28-day cycles of maintenance lenalidomide 10 mg (days 1-21).
The rate of minimal residual disease-negative remissions were 70.4% (95% CI: 56.4%-82.0%),) and sustained, with a median duration of 5.5 years (95% CI: 3.7 years to not estimable). The probability of being free from progression to multiple myeloma was 91.2% (95% CI: 67.4%-97.9%), and no deaths occurred. In other words, progression to myeloma was low (9%)
These findings suggest that treatment of high-risk smoldering myeloma with KRd triplet regimen may alter the natural history of smoldering myeloma by significantly delaying the development of end-organ disease. Patients with smoldering myeloma may be encouraged to enrol in trials evaluating novel multidrug combinations like KRd or others. However, and although these results are promising, this regimen should not be used as standard care, and randomized clinical trials are needed to confirm this favourable benefit-to-risk profile.
Kazandjian D, Hill E, Dew A et al. Carfilzomib, Lenalidomide, and Dexamethasone Followed by Lenalidomide Maintenance for Prevention of Symptomatic Multiple Myeloma in Patients With High-risk Smoldering Myeloma: A Phase 2 Nonrandomized Controlled Trial. JAMA Oncol. 2021 Sep 16;e213971.