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Despite the effectiveness of plasma exchange (PEX) and immunosuppressants in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a number of patients still die as a result of the disease. Whether caplacizumab could rescue these patients remains still unsettled. The objective of this study was to characterise mortality patterns and prognostic factors in the first episode of aTTP. We queried the Spanish TTP Registry for patients with a diagnosis of aTTP in their presenting episode who fulfilled complete clinical and follow-up data (n = 102). The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Clinical and laboratory data were analysed at diagnosis and during the treatment course. Eight patients (7.7%) died between 12 h and 36 days after presentation, and could be classified into three patterns: death before treatment, early death driven by acute cardiac or neurologic events, and late death due to unremitted aTTP. Stupor or coma at diagnosis and platelet count < 20 x 10(9) /L by the 6th treatment day were independently associated with increased risk of death. Stupor or coma at diagnosis and lack of response to PEX by the 6th day in patients experiencing the first episode of aTTP are strong predictors of mortality. These patients could be rescued by novel agents aimed at halting the microvascular thrombosis until adequate immunosuppression is achieved.

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody-drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptormodified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

Introduction : Combinations of proteasome inhibitors, immunomodulators, and monoclonal antibodies are highly active against multiple myeloma. Consequently, several combinations have moved from the relapsed to the front-line setting. In the context of lenalidomide and bortezomib being used upfront, salvage options need to be evaluated. Areas covered : This manuscript reviews available data for the treatment of patients progressing on optimal frontline strategies, with a focus on the role of second-generation proteasome inhibitors and immunomodulators, monoclonal antibodies and immunotherapy. Expert opinion : Remarkable progress has been made in myeloma treatment due to the integration of immunomodulators, proteasome inhibitors and more recently monoclonal antibodies in the front-line setting. However, we work on the assumption that most individuals will eventually relapse. Optimized upfront therapy negatively selects more resistant patients among still relapsing individuals. Bortezomib and lenalidomide-exposed patients are under-represented in trials leading to currently approved combinations. Evidence needs to be reviewed taking into account how the improvement of frontline therapy has modified the characteristics of patients at the time of relapse. Second generation immunomodulatory agents and proteasome inhibitors, monoclonal antibodies and other agents have shown efficacy in this new landscape. Immunotherapeutic agents, including CAR-T cells are promising for patients failing standard combinations, despite current data are still immature.

This research presents a system, currently under development, which aims at providing an intelligent ambient able to improve the quality of life and delivering customized support to elderly people in need of assistance, according to their own specific situation, and in a non-intrusive and respectful way. (10 refs.)

Schönlein-Henoch purpura is a vasculitis due to hypersensitivity characteristic of the infancy that affects preferably small vessels. The etiology is unknown, although it has been related to allergic reactions to drugs, infections, vaccines and insecta bites. An adult with a Schönlein-Henoch purpura after receiving spiramicin is presented, beginning with epigastric pain and vomiting and the purpura appearing subsequently.