Gain of Chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone

Abstract

Gain of chromosome 1q (+1q) is commonly identified in multiple myeloma and has been associated with inferior outcomes. However, the prognostic implication of +1q has not been evaluated in the setting of standard triplet regimens. We retrospectively analyzed 201 consecutive patients with newly diagnosed myeloma who received induction with lenalidomide, bortezomib, and dexamethasone (RVD) and were tested for +1q at diagnosis by fluorescent in-situ hybridization. Patients with +1q (n = 94), compared to those without +1q (n = 107), had shorter median progression-free survival (PFS) (41.9 months vs 65.1 months, p = 0.002, HR = 1.90) and overall survival (median not reached (NR) for either arm, p = 0.003, HR 2.69). In subgroup analyses, patients with co-occurring +1q and t(4;14), t(14;16) or del(17p) or with 4 or more copies of 1q had significantly worse PFS (25.1 months and 34.6 months, p < 0.001 and p = 0.0063, respectively), whereas patients with three copies and no other high-risk cytogenetic abnormalities had no significant difference in PFS. These data suggest that when treated with RVD induction, patients with +1q should be considered at very high risk for early progression in multiple myeloma when ≥4 copies are detected or in the context of other high-risk cytogenetic abnormalities.

Patient Similarity Network of Multiple Myeloma Identifies Patient Sub-groups with Distinct Genetic and Clinical Features

“…Gain(1q) is observed in ~40% of MM cases and in several other types of cancer, including breast cancer, hepatocellular carcinoma and myeloproliferative neoplasms, and has been the subject of numerous studies in the past decade [40][41][42][43] . A recent study has shown that newly diagnosed MM patients with gain of 1q who received induction therapy with bortezomib, lenalidomide and dexamethasone (VRD) are at higher risk of early relapse, especially when amp(1q) is detected 28 . Another study found that relapsed/refractory MM patients (RRMM) with gain of 1q have worse outcomes after treatment with Daratumumab 44 .…”

“…3A, 3B). Since the number of 1q copies has been previously reported as being prognostically relevant 28,29 , we evaluated it across all the subgroups. Sub-group 2e had the highest number of copies (p=0.0001) (Supp Fig.…”

Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China

“…Nevertheless, another study published by Fonseca found that 1q21 gain lost its independent prognostic value in multivariate analysis, 16 which indicated that the adverse impact of 1q21 gain might be contributed to other high‐risk factors. As to the era of novel agents, although the response rate and survival of MM have been largely improved, most studies supported the conclusion that 1q21 gain was an adverse indicator in patients treated with novel agents and ASCT, 26,27 while some demonstrated that 1q21 gain lost its prognostic value in bortezomib‐treated patients 28 . A study of Asian patients analyzed the role of 1q21 gain in different treatment strategies, and found that the presence of 1q21 gain deterred PFS to bortezomib and lenalidomide, while ASCT was also less effective in patients with 1q21 gain 29 .…”

Patient Similarity Network of Newly Diagnosed Multiple Myeloma Identifies Patient Sub-groups with Distinct Genetic Features and Clinical Implications

“…3C, 3D). Since the number of 1q copies has been previously reported as being prognostically relevant, we evaluated it across all the sub-groups 22,23 . Sub-group 2e had the highest number of copies (p=0.0001) (Supp Fig.…”