Patients with transplant-eligible NDMM were equally randomized to receive three 42-day cycles of RVd (lenalidomide 25 mg/d p.o., d1–14 and d22-35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33) in both study arms. Isa was added to Isa-RVd as follows: 10 mg/kg i.v., cycle 1: d 1, 8, 15, 22, 29; cycles 2-3: d 1, 15, 29....Similar results were observed for Isa-RVd vs. RVd among the common major single high-risk cytogenetic features:...t(4;14): 57.6% (19/33) vs. 47.1% (16/34), OR=1.53, 95% CI: 0.58-4.06...Isa-RVd induction therapy is superior to RVd in patients with transplant-eligible NDMM and high-risk or ultra high-risk cytogenetics, consistent with the benefit observed in the overall trial population.