Browsing by Author "Katodritou, Eirini (12797161700)"

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.

Background: Multiple myeloma (MM) is predominantly a disease of the elderly, but approximately 10% of patients are younger than 50 years at diagnosis. Methods: This study aimed to investigate the clinical characteristics, treatment outcomes, and prognostic factors in younger MM patients using retrospective data from the Balkan Myeloma Study Group registry. Results: A total of 350 patients under 50 years old were included, comprising 10.4% of the overall cohort. The study found that younger patients had lower rates of renal impairment and anemia but a higher incidence of lytic bone disease and adverse cytogenetics. Treatment regimens, including proteasome inhibitors and immunomodulatory agents, were comparable between younger and older patients, but younger patients had significantly better complete response rates and overall survival (OS). The 5- and 10-year OS rates were 76% and 64%, respectively, with a projected median OS exceeding 15 years. Factors such as anemia, hypercalcemia, and high-risk cytogenetics were associated with worse survival outcomes. Autologous stem cell transplantation (ASCT) emerged as a key contributor to improved progression-free survival (PFS) and OS. Conclusion: In conclusion, younger MM patients exhibit distinct disease features and benefit from intensified treatment approaches, underscoring the need for tailored therapies to achieve potential disease cure. © 2025 The Author(s)

Background: Multiple myeloma (MM) is predominantly a disease of the elderly, but approximately 10% of patients are younger than 50 years at diagnosis. Methods: This study aimed to investigate the clinical characteristics, treatment outcomes, and prognostic factors in younger MM patients using retrospective data from the Balkan Myeloma Study Group registry. Results: A total of 350 patients under 50 years old were included, comprising 10.4% of the overall cohort. The study found that younger patients had lower rates of renal impairment and anemia but a higher incidence of lytic bone disease and adverse cytogenetics. Treatment regimens, including proteasome inhibitors and immunomodulatory agents, were comparable between younger and older patients, but younger patients had significantly better complete response rates and overall survival (OS). The 5- and 10-year OS rates were 76% and 64%, respectively, with a projected median OS exceeding 15 years. Factors such as anemia, hypercalcemia, and high-risk cytogenetics were associated with worse survival outcomes. Autologous stem cell transplantation (ASCT) emerged as a key contributor to improved progression-free survival (PFS) and OS. Conclusion: In conclusion, younger MM patients exhibit distinct disease features and benefit from intensified treatment approaches, underscoring the need for tailored therapies to achieve potential disease cure. © 2025 The Author(s)

Background: The primary analysis of the APOLLO trial, done after a median follow-up of 16·9 months, showed that daratumumab plus pomalidomide and dexamethasone significantly improved progression-free survival versus pomalidomide and dexamethasone. Here, we report the final overall survival and updated safety results from APOLLO. Methods: APOLLO was an open-label, randomised, phase 3 trial conducted at 48 academic centres and hospitals across 12 countries in Europe, that included adults aged 18 years or older with relapsed or refractory multiple myeloma who had an ECOG performance status score of 0–2, had received at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if they had received only one previous line of therapy. An interactive web-response system was used to randomly assign patients (1:1) to receive daratumumab plus pomalidomide and dexamethasone or pomalidomide and dexamethasone; patients were stratified by the number of previous lines of therapy and International Staging System disease stage. Oral pomalidomide (4 mg once daily; days 1–21) and dexamethasone (40 mg once daily; days 1, 8, 15, and 22) were given in 28-day cycles until disease progression or unacceptable toxicity. Daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) was administered weekly (cycles 1–2), every 2 weeks (cycles 3–6), and every 4 weeks thereafter. The primary endpoint of progression-free survival, which has previously been reported, and the pre-planned secondary endpoint of overall survival were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT03180736) and is no longer enrolling patients. Findings: Between June 22, 2017, and June 13, 2019, 304 patients were randomly assigned: 151 to the daratumumab plus pomalidomide and dexamethasone group and 153 to the pomalidomide and dexamethasone group. The median age was 67 years (IQR 60–72); 143 (47%) patients were female and 161 (53%) were male, and 272 (89%) were White. At a median follow-up of 39·6 months (IQR 37·1–43·7), median overall survival was 34·4 months (95% CI 23·7–40·3) in the daratumumab plus pomalidomide and dexamethasone group versus 23·7 months (19·6–29·4) in the pomalidomide and dexamethasone group (hazard ratio [HR] 0·82 [95% CI 0·61–1·11]; p=0·20). The most common grade 3–4 treatment-emergent adverse events were neutropenia (103 [69%] of 149 with daratumumab plus pomalidomide and dexamethasone vs 76 [51%] of 150 with pomalidomide and dexamethasone), anaemia (27 [18%] vs 32 [21%]), and thrombocytopenia (27 [18%] vs 28 [19%]). Serious treatment-emergent adverse events occurred in 80 (54%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group and in 60 (40%) of 150 patients in the pomalidomide and dexamethasone group, the most common of which was pneumonia (23 [15%] of 149 vs 13 [9%] of 150). Treatment-emergent adverse events resulting in death occurred in 13 (9%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group and in 13 (9%) of 150 patients in the pomalidomide and dexamethasone group, with 4 (3%) of 151 adverse events leading to death within 30 days of the last treatment dose thought to be related to study treatment in the daratumumab plus pomalidomide and dexamethasone group (septic shock [n=1]; sepsis [n=1]; bone marrow failure, campylobacter infection, and liver disorder [n=1]; and pneumonia [n=1]) and none in the pomalidomide and dexamethasone group. Interpretation: Although the difference in overall survival observed between treatment groups was not significant, the safety profile results with long-term follow-up reported here continue to support the use of daratumumab plus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. Funding: European Myeloma Network and Janssen Research & Development. © 2023 Elsevier Ltd

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