Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma

Abstract

PURPOSE Observation is the current standard of care for smoldering multiple myeloma. We hypothesized that early intervention with lenalidomide could delay progression to symptomatic multiple myeloma. METHODS We conducted a randomized trial that assessed the efficacy of single-agent lenalidomide compared with observation in patients with intermediate- or high-risk smoldering multiple myeloma. Lenalidomide was administered orally at a dose of 25 mg on days 1 to 21 of a 28-day cycle. The primary end point was progression-free survival, with disease progression requiring the development of end-organ damage attributable to multiple myeloma and biochemical progression. RESULTS One hundred eighty-two patients were randomly assigned—92 patients to the lenalidomide arm and 90 to the observation arm. Median follow-up is 35 months. Response to therapy was observed in 50% (95% CI, 39% to 61%) of patients in the lenalidomide arm, with no responses in the observation arm. Progression-free survival was significantly longer with lenalidomide compared with observation (hazard ratio, 0.28; 95% CI, 0.12 to 0.62; P = .002). One-, 2-, and 3-year progression-free survival was 98%, 93%, and 91% for the lenalidomide arm versus 89%, 76%, and 66% for the observation arm, respectively. Only six deaths have been reported, two in the lenalidomide arm versus four in the observation arm (hazard ratio for death, 0.46; 95% CI, 0.08 to 2.53). Grade 3 or 4 nonhematologic adverse events occurred in 25 patients (28%) on lenalidomide. CONCLUSION Early intervention with lenalidomide in smoldering multiple myeloma significantly delays progression to symptomatic multiple myeloma and the development of end-organ damage.

Recent Advances in the Management of Smoldering Multiple Myeloma

“…A total of 182 patients were randomized to lenalidomide 25 mg daily for 21 of the 28 days cycle (n = 90) or observation (n = 92). The 3-year PFS was 91% for lenalidomide group versus 66% for the observation arm (HR 0.28, P = 0.0005) favoring lenalidomide arm, significantly delaying the progression of smoldering myeloma [40]. No difference existed in the quality of life between both groups.…”

“…Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant (ASCENT) is a phase 2 trial currently recruiting patients to evaluate the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in an attempt to cure patients with high-risk SMM [29]. The completed clinical trials were summarized in Table 5 [30][31][32][33][34][36][37][38][39][40]. The ongoing clinical trials were summarized in Table 6 [29,43,[47][48][49][50][51][52][53][54].…”

Next-Generation Sequencing for Clinical Management of Multiple Myeloma: Ready for Prime Time?

“…The current clinical approach to SMM is watch-and-wait. However, evidence in favor of early treatment is growing, at least for high-risk stages (28,90,91). Therefore, improved prognostic scores that could reliably identify high-risk SMM would address a growing clinical need.…”

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

“…The efficacy of lenalidomide was also shown in the phase II/III E3A06 study, in which lenalidomide was compared to observation in SMM [62]. After a median follow-up of 35 months in phase III of the trial, the overall response rate (ORR) was 50% in the R group and 0% in the observational group.…”