Primary failure of bortezomib in newly diagnosed multiple myeloma--understanding the magnitude, predictors, and significance.

Botezomib-based induction is highly effective for the treatment of newly diagnosed multiple myeloma (NDMM). We investigated the outcomes of NDMM patients who failed to respond to bortezomib-based induction in a 'real-life' clinical setting. In a cohort of 295 consecutive NDMM patients in 3 medical centers, 74 (25%) failed to achieve at least partial response after 4 induction cycles, and were classified as non-responsive. Compared to induction responders, they were older, more frequently anemic, had a higher incidence of del17p and ISS-3, and a worse performance status. In multivariable analysis, bortezomib-based induction failure occurred in 25% of patients and was the strongest independent factor predicting mortality with a 5-fold hazard ratio (95% CI 1.44-8.68). Three-year overall survival in responsive vs. non-responsive patients were 76% vs. 53%, respectively (p < 0.0001). Survival from time of salvage second-line treatment was significantly shorter among induction non-responders vs. responders (25 months vs. not-reached, p = 0.024).