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Although multiple myeloma (MM) remains an incurable hematological malignancy, the introduction of autologous stem cell transplantation, proteasome inhibitors, and immunomodulatory agents has increased the survival of patients. However, most patients will become refractory to available therapeutic regimens. Moreover, conventional strategies have shown limited benefit in high‐risk patients with adverse cytogenetics. Therefore, novel strategies including immunotherapy are needed to improve the outcomes of these patients. Immunotherapy includes a range of strategies to redirect the immune system to attack tumor cells. Here, we review the most promising immunotherapy strategy published to date for many hematologic malignancies, chimeric antigen receptor (CAR) T cells. Most clinical studies of CAR T cell therapy for MM target B‐cell maturation antigen (BCMA) on malignant plasma cells. The initial studies using BCMA targeted CAR T cells are devoted to patients with advanced relapsed/refractory MM. Eventual relapse after CAR T‐cell therapy remains an issue. We present the most recent clinical data, as well as relevant preclinical data demonstrating novel strategies with the potential to improve clinical outcomes of cellular therapy for MM. Further, we present a proposal for how CAR T‐cell therapy may fit into the future therapeutic landscape of MM as adoptive cellular therapy moves beyond the currently studied multiply relapsed/refractory setting. [ABSTRACT FROM AUTHOR]

Background: We described the real‐life epidemiology and causes of infections on the different therapy phases in patients undergoing chimeric antigen receptor (CAR) T‐cells directed towards CD19+ or BCMA+ cells. Methods: All consecutive patients receiving CAR T‐cell therapy at our institution were prospectively followed‐up. We performed various comparative analyses of all patients and subgroups with and without infections. Results: Ninety‐one adults mainly received CAR T‐cell therapy for acute leukaemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non‐neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 [38%] cases), endogenous source (5 [17%]), and Clostridioides difficile (5 [17%]). Patients receiving corticosteroids after CAR T‐cell therapy had a higher risk of endogenous infection (100% vs. 16%; p =.006). During the non‐neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%). Conclusions: Infections after CAR T‐cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates. [ABSTRACT FROM AUTHOR]

Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors. [ABSTRACT FROM AUTHOR]

Dear Editor, Despite the improved survival of patients with amyloid light-chain (AL) amyloidosis in the last decades [[1]], the role of kidney transplantation (KT) in patients with amyloidosis-associated end-stage renal disease (ESRD) remains controversial [[3]]. All three achieved complete renal function recovery during the first week, but two patients developed allograft dysfunction due to the recurrence of AL amyloidosis, both confirmed by kidney biopsy. [Extracted from the article]