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The course of multiple myeloma (MM) is influenced by a variety of factors, including the specificity of the tumour microenvironment (TME). The aim of this review is to provide insight into the interplay of treatment modalities used in the current clinical practice and TME. Bortezomib-based triplets are the standard for MM first-line treatment. Bortezomib is a proteasome inhibitor (PI) which inhibits the nuclear factor kappa B (NF-kappa B) pathway. However, bortezomib is decreasing the expression of chemokine receptor CXCR4 as well, possibly leading to the escape of extramedullary disease. Immunomodulatory drugs (IMiDs), lenalidomide, and pomalidomide downregulate regulatory T cells (Tregs). Daratumumab, anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody (MoAb), downregulates Tregs CD38+. Bisphosphonates inhibit osteoclasts and angiogenesis. Sustained suppression of bone resorption characterises the activity of MoAb denosumab. The plerixafor, used in the process of stem cell mobilisation and harvesting, block the interaction of chemokine receptors CXCR4-CXCL12, leading to disruption of MM cells' interaction with the TME, and mobilisation into the circulation. The introduction of several T-cell-based immunotherapeutic modalities, such as chimeric-antigen-receptor-transduced T cells (CAR T cells) and bispecific antibodies, represents a new perspective in MM treatment affecting TME immune evasion. The optimal treatment approach to MM patients should be adjusted to all aspects of the individual profile including the TME niche.

Background: Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease in which red blood cells (RBC) are targeted by autoantibodies confirmed with positive direct antiglobulin test (DAT), resulting in premature destruction of RBC. AIHA may be subdivided into warm antibody AIHA (wAIHA) and cold antibody AIHA (cAIHA), and also to primary and secondary depending on the presence of an underlying disorder. In addition to that, patients may have positive DAT but without features of hemolysis, and some of them will later develop AIHA. Aims: The aim of this study was to analyze characteristics of newly diagnosed DAT positive AIHA patients during the 5 years period in our tertiary center, as well to assess DAT positive patients without features of AIHA. Methods: This was a single-center retrospective cohort study performed at the University Hospital Center (UHC) Zagreb, Zagreb, Croatia, Department of Internal Medicine, Division of Hematology. We included data for all consecutive adult patients with a newly diagnosis of DAT positive AIHA between 2014 and 2018, and also all DAT positive patients without features of hemolysis in that time period. This study was approved by the UHC Ethical Committee. Descriptive statistics was performed and included means ± SD or median (range) as appropriate for continuous variables and frequency (percentage) for categorical variables. Results: The data from 56 patients (50% women) with newly diagnosed DAT positive AIHA during the study period were analyzed. The median age at time of AIHA diagnosis was 67 years (range 22–90 years). Majority of AIHA was wAIHA (51 (91.1%) patients). AIHA was considered primary in only 14 (25%) patients and was associated with an underlying disorder in 42 (75%) patients. The various disorders were associated with secondary wAIHA, the most frequently B-cell lymphoproliferative malignant diseases (33%), solid tumors (9.8%), myelodisplastic syndrome (9.8%) and autoimmune diseases (9.8%). Median hemoglobin level at the AIHA diagnosis was 71 g/L. 82.1% of patients received RBC transfusion. Seven (12.5%) patients did not require immunosuppressive treatment and other received mostly corticosteroids as the 1st line of therapy. Rituximab received 9 patients (17.6%) with wAIHA, mostly as the 2nd line of treatment. Eight patients (14.3%) with AIHA developed thrombosis (7 with wAIHA and 1 with cAIHA). During the 5-years study period additional 120 patients with DAT positive results but without signs of hemolysis were detected. Summary/Conclusion: Data from our 5-years single centre experience with AIHA are comparable with literature data. Majority of patients had secondary AIHA and wAIHA. Rituximab is used mostly as the second-line treatment and corticosteroid-sparing agent for wAIHA. Significant number of patients with DAT positive results but without features of hemolysis was detected, and they need to be closely monitored for possible development of AIHA.