Cytogenetic and clinical marks for defining high-risk myeloma in the context of bortezomib treatment

Multiple myeloma (MM) is a heterogeneous disease, and the benefit from bortezomib treatment is not uniform among all patients subgroups. Currently, little information is available to predict patients response to bortezomib treatment. In this study, we aimed to identify patients benefiting minimally from bortezomib as part of first-line therapy and to define high-risk MM in the context of bortezomib treatment. We compared the effect of a bortezomib-based treatment (arm B) with that of a treatment without bortezomib (arm A) on different genetic patient subgroups in a series of 273 cases of newly diagnosed MM. These patients were enrolled in a prospective, non-randomized clinical trial (BDH 2008/02). A subgroup of patients exhibiting little benefit from bortezomib treatment was identified. These patients had at least one of the following characteristics: del(17p13), 1q21 gain, or high lactate dehydrogenase levels. In this subgroup, survival of patients treated with bortezomib was comparable (progression-free survival: 14.0 vs. 15.0 months, p = 0.992; overall survival: 21.0 vs. 14.0 months, p = 0.472) to that of patients undergoing thalidomide-based treatment. We propose that all patients with newly diagnosed MM should be evaluated for these three markers before bortezomib treatment. Other novel drugs and alternative therapeutic strategies are needed for patients with such markers.