Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplantation in multiple myeloma

Laura Rosiñol, Albert Oriol, Rafael Rios, Anna Sureda, María-Jesús Blanchard, Miguel Teodoro Hernández, Rafael Martínez-Martínez, Jose M Moraleda, Isidro Jarque, Juan Bargay, Mercedes Gironella, Felipe de Arriba, Luis Palomera, Yolanda Gonzalez-Montes, Josep Marti, Isabel Krsnik, Jose M Arguiñano, Maria-Esther Gonzalez, Ana Pilar Gonzalez, Luis Felipe Casado, Lucia Lopez-Anglada, Bruno Paiva, Maria-Victoria Mateos, Jesus San Miguel, Juan-José Lahuerta and Joan Bladé

Key Points

  • VRD was highly effective and well tolerated before ASCT, achieving 33.4% CR and 28.8% MRD-undetectable rates after 6 cycles of induction.

  • Responses deepened with VRD throughout induction and over the course of treatment with few discontinuations due to toxicity.


Achieving and maintaining high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients {less than or equal to} 65 years old with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with intravenous busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the {greater than or equal to} very good partial response rates were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10−6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade {greater than or equal to} 3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade {greater than or equal to} 2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at (NCT01916252) and EudraCT (2012-005683-10).

  • Submitted February 19, 2019.
  • Revision received September 4, 2019.
  • Accepted August 2, 2019.