Multiple myeloma: 2022 update on diagnosis, risk stratification, and management

Abstract

Disease Overview: Multiple myeloma accounts for approximately 10% of hematologic malignancies. Diagnosis:The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsyproven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Risk Stratification:The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. The presence of any two high risk factors is considered double-hit myeloma, and three or more high risk factors is triple-hit myeloma.Risk-Adapted Initial Therapy: In patients who are candidates for autologous stem cell transplantation, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard-risk patients can collect stem cells, get additional cycles of induction therapy, and delay transplant until first relapse. Patients who are not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression.Maintenance Therapy: Standard-risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma.Management of Relapsed Disease: A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse.

Single‐cell transcriptome profiling reveals the key role of ZNF683 in natural killer cell exhaustion in multiple myeloma

“…Among MM patients selected, 50% of the patients had high‐risk cytogenetic abnormalities, and most patients were at intermediate/high stages (≥ Stage II) of disease, assessed by ISS (70%) and R‐ISS (80%) stage systems. 36 …”

“…Among MM patients selected, 50% of the patients had high-risk cytogenetic abnormalities, and most patients were at intermediate/high stages (≥ Stage II) of disease, assessed by ISS (70%) and R-ISS (80%) stage systems. 36 A total of 2,41,440 single cells were divided into 13 clusters (Figure S1B,C). These clusters mainly included T cells, monocytes/macrophages, plasma cells, NK cells, and a small proportion of B cells.…”

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

“…1q21 + can be divided into gain (gain1q) or amplification of 1q21 (amp1q), respectively, if three or more than three copies of 1q21 are detected, and the distinction between these two categories has increasingly become more important since the copy number of 1q21 seems to reflect the genomic instability, proliferation rate, drug resistance, and early progression/death rate of the disease [1,3,4]. Nevertheless, the optimal management of 1q21 + patients in the era of novel therapies has yet to be determined [1,5,6]. Daratumumab, an anti-CD38 monoclonal antibody, has provided clear demonstration of efficacy in MM patients, even among high-risk (HR) MM patients, and is now licensed for use in relapsed-refractory MM (RRMM) as well as newly diagnosed MM (NDMM) [7,8].…”

Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine—Are We There Yet?

“…When in the presence of a combined therapy regimen, defining a dose–response function becomes more complex, since the synergetic effect must be considered, requiring, in addition to the effects of single agents, the inclusion of functions that define the effect due to the interaction of the drugs. Importantly, most patients are treated with triple therapies [ 163 ]. Therefore, testing the combined effect of more than two agents should be the next step to obtain a more accurate model.…”