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Background: The duration of response to treatment is a major prognostic factor, and early relapse (ER) strongly predicts inferior survival in multiple myeloma (MM). However, the definitions of ER in MM vary from study to study and how to dynamically integrate risk distribution is still unsolved. Methods: This study evaluated these ER definitions and further investigated the underlying relationship with static risk distribution in 629 newly diagnosed MM (NDMM) patients from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Results: These data indicated that early relapse within 18 months (ER18) after initial treatment was the best time point for identifying early progression and dynamic high‐risk in MM. The ER18 population (114 of 587, 19.4%) presented with more aggressive biologic features and the inferior response to treatment compared to a reference cohort (p <.001), with a significantly short median overall survival (OS) of 28.9 months. Multivariate analyses confirmed the most significant prognostic value of ER18 on OS in the context of International Staging System stage, elevated lactate dehydrogenase, thrombocytopenia, cytogenetic abnormalities, and treatment (hazard ratio, 4.467; p <.001). The authors also described the specific transitions from static risk profile to dynamic risk distribution and then constructed a mixed‐risk‐pattern to identify four novel populations with distinct survival (p <.001). Additionally, the authors proposed a second‐state model that predicts dynamic risk changes, enabling a complementary role to the Revised International Staging System model in facilitating individualized systematic treatment. Conclusions: Collectively, this study concludes that ER18 is a simple and dynamic prognostic predictor in MM. In addition to static risk assessment, dynamic risk plays an important role in survival prediction. The present study sheds light on the optimal time point for early relapse (ER), defined as relapse within 18 months after initial treatment, and highlights its significant dynamic predictive impact on the prognosis in multiple myeloma. Alongside the conventional static risk stratification at diagnosis, a second‐state model that incorporates ER reveals dynamic risk changes that facilitate individualized systematic treatment. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a rare subtype of non‐Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In‐depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD‐1/PD‐L1&PD‐L2, TIGIT/PVR, CD137/CD137‐L, CTLA‐4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long‐term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and perceptions of prognosis by line of therapy are lacking. Methods: The authors conducted a cross‐sectional, multisite study of patients undergoing treatment for MM (excluding maintenance) between June 2020 and January 2021. The authors conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first‐line therapy; 2) 2 to 3 lines; and 3) 4 or more lines. Patients completed validated questionnaires to assess their QOL, fatigue, psychological distress, and perceptions of prognosis. Results: A total of 180 patients with MM were enrolled (newly diagnosed [n = 60], 2 to 3 lines [n = 60], and ≥4 lines of therapy [n = 60]). QOL, symptom burden, and fatigue scores did not differ by lines of therapy. There were no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post‐traumatic stress disorder symptoms were 23.9% (43 of 180), 23.9% (43 of 180), and 24.4% (44 of 180), respectively. Most patients (84.7%, 149 of 176) reported that their oncologist told them their cancer was incurable, but only 30.6% (53 of 173) acknowledged that they were terminally ill, and 42.0% (73 of 174) reported that they thought their cancer was incurable. Conclusions: Patients with MM undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, regardless of line of therapy. A substantial proportion of patients with MM have significant misperceptions about their prognosis and the curability of their illness despite reporting being informed of the prognosis by their oncologist. Lay Summary: This study discusses 180 patients with MM (newly diagnosed [n = 60], 2‐3 lines [n = 60], and ≥4 lines of therapy [n = 60]). Quality of life, symptom burden, and fatigue scores do not differ by lines of therapy. There are also no statistically significant differences in psychological distress by line of therapy.The rates of clinically significant depression, anxiety, and post‐traumatic stress disorder symptoms are 23.9%, 23.9%, and 24.4%, respectively.Most patients (84.7%) report that their oncologist told them their cancer was incurable, but only 30.6% acknowledge that they are terminally ill, and 42.0% report that they thought their cancer was incurable. Patients with multiple myeloma undergoing treatment experience impaired quality of life and elevated psychological distress across the disease continuum. Although the majority reported that their oncologist had told them that their cancer is incurable, a substantial proportion still reported that they believed their cancer was curable. [ABSTRACT FROM AUTHOR]

Summary: In this review, two types of soft‐tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high‐risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor‐based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor‐based regimen such as lenalidomide‐bortezomib‐dexamethasone (RVD) may be the best option, while for those eligible for high‐dose therapy a myeloma/lymphoma‐like regimen such as bortezomib, thalidomide and dexamethasone (VTD)‐RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high‐unmet need population. [ABSTRACT FROM AUTHOR]