Outcomes of patients with multiple myeloma harboring chromosome 1q gain/amplification in the era of modern therapy

Abstract

Chromosome 1q gain/amplification (1q +) has been reported to be associated with inferior outcomes in multiple myeloma (MM) patients. Big therapeutic advances have shifted the treatment landscape by introducing monoclonal antibodies. There is a relative lack of data on outcomes in patients harboring this alteration in the era of monoclonal antibodies. Baseline characteristics and therapy-related data from newly diagnosed MM patients harboring 1q + detected by fluorescence in situ hybridization (FISH) were collected in a single institution. Among 34 identified subjects, the presence of elevated LDH was found to be associated with shorter overall survival (OS), and increased bone marrow plasma cell percentage (≥ 60%) was associated with worse progression-free survival (PFS). 1q + copy number more than three was associated with both shorter OS and PFS. Additionally, the administration of lenalidomide was associated with superior OS. The use of autologous stem cell transplantation, bortezomib, or daratumumab, was found to have no prognostic benefits in our sample. Lenalidomide may be an optimal therapeutic choice for this population, and future larger studies are warranted to confirm this benefit and further investigate the role of monoclonal antibodies in this subpopulation.

Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens

“…We report a real-world retrospective study of the prognosis and efficacy of 1q21 gain in patients with newly diagnosed multiple myeloma who received bortezomib-based chemotherapy. We found that 1q21 gain is common (45.9%) at diagnosis in multiple myeloma, and this aberration is associated with later ISS stage levels, lower serum albumin levels, and elevated LDH concentrations, consistent with previous research results ( 3 , 8 , 16 ). Moreover, we further demonstrated the prognostic risk value of 1q21 gain in PFS and OS in MM patients.…”

“…Highrisk copy number gains of 1q21 partly originate from the hypomethylation of 1q12 pericentromeric heterochromatin (7). Nevertheless, the prognostic value of chromosome 1q21 aberrations is still controversial among cytogenetic abnormality studies (8)(9)(10)(11)(12).…”

Primary outcomes by 1q21+ status for isatuximab-treated patients with relapsed/refractory multiple myeloma: subgroup analyses from ICARIA-MM and IKEMA

“…11 A recent report found no prognostic benefit of daratumumab-based therapy on the outcome of 1q21+ newly diagnosed MM patients in a real-world setting, though this study has limitations because of its relatively small sample size and its retrospective, single-center nature. 12 Overexpression of complement regulatory proteins CD55 and CD59 has been implicated in daratumumab resistance. 13 Interestingly, the gene encoding CD55 is localized to 1q32.2, and overexpression of CD55 has been suggested to contribute to daratumumab resistance in 1q21+ patients.…”

“… 11 A recent study found no prognostic benefit of daratumumab-based therapy on the outcome of newly diagnosed MM patients with 1q21+ in a real-world setting, although the study had limitations because of its relatively small sample size and its retrospective, singlecenter nature. 12 …”

Adverse outcome associated with daratumumab-based treatments in relapsed/refractory multiple myeloma patients with amplification of chromosome arm 1q21: a single-center retrospective experience

“…However, data supporting the effectiveness of adjunctive daratumumab in 1q21 + patients are scarce, since pivotal trials didn’t report outcomes on this patient population, and potential mechanisms of resistance conferred by 1q21 + to daratumumab therapy have been proposed [ 1 ]. Interestingly, Hu and colleagues [ 9 ] have recently published a retrospective study describing real-world outcomes of 34 NDMM patients harboring 1q21 + , reporting no prognostic role of daratumumab therapy and worse outcomes for amp1q patients compared to gain1q patients. As the authors noted, only one study by Mohan and colleagues [ 10 ] had previously investigated the outcomes of 1q21 + patients treated with daratumumab, reporting poor prognosis associated with both 1q21 + and GEP-70 HR status, although patients in that study were heavily pretreated and only 63% of them received daratumumab in combinations with immunomodulatory drugs.…”