Gain(1)(q21) is an Unfavorable Genetic Prognostic Factor for Patients With Relapsed Multiple Myeloma Treated With Thalidomide but Not for Those Treated With Bortezomib

Chromosome 1 abnormalities in elderly patients with newly diagnosed multiple myeloma treated with novel therapies

“…This finding confirms and emphasizes the already reported beneficial role of bortezomib, which seems to overcome the negative impact of poor prognostic cytogenetic features. 29,31,33 This was demonstrated not just in the study by Palumbo et al, 31 but also in the bortezomib-based trial by Harousseau et al, 34 which showed a similar progressionfree survival between cytogenetically defined high-risk and standard-risk patients. Moreover, the Spanish VISTA trial 35 , comparing MP and VMP, showed that, in the VMP subgroup, there was no statistically significant difference in overall survival between high-risk and standard-risk patients.…”

“…Smetana et al 29 analyzed several chromosomal abnormalities in 102 patients with relapsed MM treated with bortezomib-or thalidomide-based regimens. They suggested that bortezomib should be preferred to thalidomide in patients with relapsed and/or refractory MM carrying gain(1q), two or more cytogenetic abnormalities and/or del(17p).…”

“…28 In recent investigations of the efficacy of thalidomidebased regimens in both newly diagnosed and relapsed/refractory MM patients carrying gain(1q21), it was found that thalidomide is not capable of overcoming the adverse influence of gain(1q) on survival. 29,30 This retrospective study examines the clinical impact of chr1 aberrations, other common cytogenetic abnormalities and plasma cell immunophenotype in a large series of elderly patients with newly diagnosed MM enrolled in a phase III randomized trial comparing VMP versus VMPT followed by VT maintenance (VMPT-VT).…”

Incidence of cytogenetic aberrations in two B lineage subpopulations in multiple myeloma patients analyzed by combination of whole-genome profiling and FISH

“…Similarly, complex karyotype and non-hyperdiploidy are common genetic features with negative impact on prognosis of MM patients. Particularly the incidence of gain in chromosome 1q resulting in overexpression of CKS1B and ANPE 32 and therefore deregulation of Nf-kappaB pathway is associated with adverse prognosis for both newly diagnosed and relapsed MM patients [30,31].…”

Plasma Cell Neoplasms

“…Poor response to bortezomib/dexamethasone [115] del(17p)/TP53 deletion Poor prognosis with lenalidomide/dexamethasone with or without bortezomib [63, 64, 116−118] Poor prognosis after autologous or allogeneic HSCT [113] del(1p) Poor response to high-dose chemotherapy [68] Gain 1q21 Poor response to lenalidomide/dexamethasone [117] Poor response to bortezomib in refractory disease [75,119] Thalidomide does not improve event-free survival of 1q21 gain at diagnosis [74] or at relapse [120] Low-risk disease Maintenance thalidomide improves outcome [121] NF-kappaB activation May respond to bortezomib; small molecule inhibitors [100] BRAF mutation BRAF inhibitors [112] primary abnormality was detected by FISH. Even in cases in which the percentage of plasma cells is <1 % by morphology or flow cytometry, the plasma cell enrichment process can yield informative results.…”