Ngai, Cheong

Introduction: Bortezomib has been reported to favourably impact the outcomes of t(4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown. Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t(14;16), t(4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells. Results: +1q identified in 167 (66.8%) and associated with t(4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t(4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069). Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM. However, myeloma outside the BM aspiration site may result in subsequent relapse despite MRD-negativity. Therefore, positron emission tomography-computed tomography (PET-CT) based on F-fluorodeoxyglucose (FDG) is a complementary tool to monitor residual disease in MM. However, FDG may miss myeloma lesions that are not FDG-avid. On the other hand, 11 C-Acetate (ACT) has been found to be a more sensitive and specific tracer than FDG in MM. Recently, the addition of daratumumab to bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, lenalidomide, dexamethasone (VRd) backbone has been proven to improve outcomes. Herein, we report three newly-diagnosed MM patients achieving deep responses with imaging CR using ACT PET in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumab-based quadruplet induction regimen.