Daratumumab continued to demonstrate single-agent clinical activity in patients with intermediate- or high-risk smoldering myeloma. No new safety concerns were observed after extended follow-up of approximately seven years, highlighting the tolerability of daratumumab. Will need phase III trials.
Early intervention in smoldering multiple myeloma (SMM) may delay progression to MM. Here, we present the final analysis of the phase 2 CENTAURUS study. In total, 123 patients with intermediate/high-risk SMM were randomized to IV daratumumab 16 mg/kg after a long-intense (n = 41), intermediate (n = 41), or short-intense (n = 41) dosing schedule. At a combined median follow-up of 85.2 months, in the long-intense, intermediate, and short-intense arms complete response or better rates were 4.9%, 9.8%, and 0%; overall response rates were 58.5%, 53.7%, and 37.5%; progressive disease/death rates were 0.096, 0.102, and 0.109 (P < .0001 for all arms); and median progression-free survival was not reached, 84.4, and 74.1 months, respectively. Median overall survival was not reached in any arm. Thirty-six patients in the long-intense or intermediate arms continued daratumumab in an optional extension phase after completing 20 cycles of per-protocol treatment. The median duration of study treatment was 44.0 (range, 1.0-91.6), 35.2 (range, 1.9-90.6), and 1.6 (range, 0.1-1.9) months in the long-intense, intermediate, and short-intense arms, respectively. No new safety signals were observed. With extended follow-up (median, ∼7 years), these data highlight the tolerability of daratumumab and support ongoing trials investigating daratumumab as an early intervention for SMM. This trial was registered at www.ClinicalTrials.gov as #NCT02316106.
Is the need to transplant declining? Salvage autologous transplant vs lenalidomide/dexamethasone offers no significant survival benefit in RRMM. Patients who relapsed were treated with high-dose chemotherapy followed by maintenance lenalidomide vs dexamethasone and lenalidomide and progression-free survival (PFS) was 20 vs 19 months.
Direct comparison of Dara+len vs. len maintenance for those with +MMR after Auto-HSCT. MRD-neg conversion rates were higher in the combo arm. This is likely going to continue gaining traction in this group of patients.
Retrospective assessment of the SWOG0777 and SWOG 1211 studies showing that dose reductions in dexamethasone did not affect outcomes. Nice to see this does not have a negative impact, as I have been doing this for years in my elderly patients who would not tolerate the ultra-high dose steroids used in these trials.
MRD at year 1 can be prognostic in pt who had AutoBMT followed by maintenance linolidomide. Please use MRD wisely … it can be expensive.
First line regimen, first quad for transplant INELIGIBLE patients, PFS at 5 years is 63% vs 45% for RVD. This will probably be the new standard of care for this population with manageable toxicity. Recall Dara RVD is for transplant eligible patients.
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