Browsing by Author "Ivanaj, Arben (6504086390)"

Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement versus extramedullary plasmacytoma at diagnosis (34.2% vs. 19.3%; P=NS.) and relapse (54.5% vs. 9%; P=0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 vs. 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached vs. 46.5 months). Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 13.6 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need. © 2020 Ferrata Storti Foundation

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-κB) 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. Sus-tained 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 recep-tors 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

We have noticed an error in the progression-free survival of patients with extramedullary plasmacytoma in our article published in Haematologica in January 2020 (doi: HAEMATOL/2019/219295). The following sentence in the abstract: “Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 13.6 months and overall survival of 11.4 months.” Should be replaced by: “Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 9.1 months and overall survival of 11.4 months.” Likewise, on page 205, the following sentence: “However, if diagnosed at relapse, PFS and OS were 13.6 months and 11.4 months for EMP compared to 20.9 months (P=0.249) and 39.8 months (P=0.093) for PO, respectively (Table 2 and Figure 1).” Should be replaced by: “However, if diagnosed at relapse, PFS and OS were 9.1 months and 11.4 months for EMP compared to 20.9 months (P=0.249) and 39.8 months (P=0.093) for PO, respectively (Table 2 and Figure 1).” The error was also present in Table 2. The corrected Table 2 is shown below. © 2021 Ferrata Storti Foundation