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Competing Interests: The authors declare no conflict of interest.

Background: The management of multiple myeloma is challenging because the disease is incurable and unexpected relapses can threaten a patient's survival. Several assessment systems are currently available, but they often require invasive or costly procedures (e.g., instrumental bone marrow and whole-body examinations) or rely on non-specific markers in blood and urine that may not be sufficient to assess and monitor the disease., Aims: To address some of these limitations, the aim of this study was to evaluate the potential use of soluble B-Cell Maturation Antigen (BCMA), a promising new serum biomarker, as a toll for moniting multiple myeloma patients., Materials & Methods: An unselected cohort of 57 newly diagnosed or relapsed myeloma patients was followed up for 6 months after starting a new therapy. Soluble BCMA levels were measured in peripheral blood using a simple and inexpensive ELISA assay., Results: Soluble BCMA was detectable in peripheral blood by a simple and inexpensive assay in all patients, even in non-secretory disease or during BCMA-targeted therapies, and significant changes in its levels were observed over time. The analysis showed that the decrease in sBCMA at 1 and 6 months reflects the quality of the clinical response to anti-myeloma regimens., Discussion & Conclusion: The data provide interesting insights into the usefulness of sBCMA as a non-invasive tool for early assessment of treatment efficacy. Its simple and cost-effective detection in peripheral blood could provide clinicians with an addiotional resource for monitoring disease progression and tailoring treatment strategies., (© 2025 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background and Aims: The positron emission tomography (PET) tracer 18F-florbetaben is a promising diagnostic tool for light-chain cardiac amyloidosis (AL-CA). A greater cardiac uptake might signal more amyloid burden and a worse outcome. We aimed to assess the prognostic significance of 18F-florbetaben uptake in AL-CA., Methods: Consecutive patients with AL-CA underwent 18F-florbetaben PET scans. Total amyloid burden (TAB; calculated as mean standardized uptake value multiplied by molecular volume) was assessed in the left and right ventricles (LV/RV) in early (5-15') and late (50-60') acquisitions. The endpoint was all-cause mortality., Results: Forty patients (median age 69 years, 73% males, Mayo 2004 stage III in 80%) underwent 18F-florbetaben PET with a median time from tissue biopsy of 21 days (interquartile range, IQR 7-83). Late LV TAB, but not early LV TAB, correlated with N-terminal pro-BNP (NT-proBNP) and hs troponin T. Over 13 months after the PET scan (IQR 5-21), 65% of patients died. A late LV TAB ≥273 cm3 (cut-off derived from spline curve analysis) predicted 18- and 24-month all-cause mortality independently from baseline variables, including NT-proBNP, hs-troponin T, and Mayo 2004 stage. Late RV TAB ≥135 cm3 independently predicted 18- and 24-month all-cause mortality. Patients with both late LV and RV TAB ≥cut-offs had a shorter survival than those with only LV TAB ≥cut-off and those with TAB in both ventricles

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who received prophylaxis (cases) were compared to those who did not (controls). The main outcome was SARS-CoV-2 infection in the subsequent 6 months. Inverse probability weighting (IPW) was used to adjust for confounders. A multivariable analysis was performed to identify variables associated with SARS-CoV-2 infection. We recruited 462 patients: 228 received prophylaxis, 234 were controls. COVID-19 was lower in cases compared to controls (16.7% vs 24.8%, p  = 0.03, after IPW 14.3% vs 24.6%, p  = 0.01). On multivariable analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, p  = 0.037) were associated with increased risk of COVID-19, while tixagevimab/cilgavimab prophylaxis (HR 0.45, 95%CI 0.27-0.73, p  = 0.001) and previous SARS-CoV-2 infection (HR 0.27, 95%CI 0.14-0.51, p  < 0.001) were protective. In conclusion, prophylaxis with monoclonal antibodies may reduce the risk of COVID-19 in hematological patients.

The presence of FLT3 mutations, including the most common FLT3-ITD (internal tandem duplications) and FLT3-TKD (tyrosine kinase domain), is associated with an unfavorable prognosis in patients affected by acute myeloid leukemia (AML). In this setting, in recent years, new FLT3 inhibitors have demonstrated efficacy in improving survival and treatment response. Nevertheless, the development of primary and secondary mechanisms of resistance poses a significant obstacle to their efficacy. Understanding these mechanisms is crucial for developing novel therapeutic approaches to overcome resistance and improve the outcomes of patients. In this context, the use of novel FLT3 inhibitors and the combination of different targeted therapies have been studied. This review provides an update on the molecular alterations involved in the resistance to FLT3 inhibitors, and describes how the molecular monitoring may be used to guide treatment strategy in FLT3-mutated AML., Competing Interests: Declaration of Competing Interest MDR consultant/speaker: Astellas, Astra Zeneca, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi-Aventis, Roche, Lilly, MSD and Ipsen. RD consultant/speaker: Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, and EUSA Pharma. All other authors report no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Light chain deposition disease (LCDD) is a rare hematologic disorder characterized by the deposition of non-amyloid monoclonal light chains in several organs. Together with renal impairment is being the primary morbidity associated with this disease. Due to its rarity, randomized clinical trials lack to explore treatment strategies and there are no approved or universally accepted standard of care treatment options. We aimed to provide a systematic summary of histological and clinical aspects of LCDD and treatment options of available literature therapies strategies. Currently, drugs used to treat multiple myeloma are recommended when LCDD patients also presented multiple myeloma. Anyway, in patients with LCDD that is not associated to multiple myeloma, haematopoietic stem cell transplantation (ASCT) and chemotherapy with thalidomide, dexamethasone, bortezomib are also recommended. In eligible patients, bortezomib-based chemotherapy followed by ASCT appears to be an effective treatment option with durable hematologic remission and organ responses. Although it appears that the patients undergoing ASCT seem to achieve deeper and durable hematologic remissions and organ responses, no statistically significant superiority can be demonstrated over non-transplant or standard chemotherapy-based approaches. As retrieved by our review, bortezomib-based therapy appears to be favorable strategy as long as no dose modification is required for renal impairment, and early hematologic responses as a recovery of renal function. Encouraging data were also demonstrated by treatment lenalidomide or melpalan based. Moreover, new myeloma treatment strategies, as monoclonal antibody Daratumumab, seem to be effective in LCDD. Instead, renal allograft is not recommended, due to high incidence of relapse., (© 2024. The Author(s).)

Light chain amyloidosis is a rare disease caused by clonal plasma cells in the bone marrow generating an excessive amount of immunoglobulin light chains. These chains misfold and produce insoluble fibrils that deposit in various organs, including the heart, kidneys, liver, nervous system, and digestive tract. Life expectancy and symptoms during the course of the disease vary depending on which and how many organs are affected. Targeted plasma cell therapy has significantly advanced the clinical management of amyloidosis, with ongoing progress. However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti-amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment., (© 2024 John Wiley & Sons Ltd.)

Multiple Myeloma remains incurable, and there is a need for therapies with novel mechanisms of action. Recently, B cell maturation antigen targeted therapy has demonstrated deep and durable responses in a largely treated population. However, the relapse rate of myeloma patients after anti-BCMA treatment strategies is increasing worldwide, and one of the most challenging issues for them is to choose the best therapy sequencing. After anti-BCMA treatment, retreatment with anti-BCMA drugs remains an option, but new targets are emerging strongly. One of them is G protein-coupled receptor, class C group 5 member D (GPRC5D), that due to the very promising data from the use of chimeric antigen receptor T-cells (CAR-T) and bispecific antibodies (BsAb) seems to be the ideal candidate in the relay of myeloma treatment at relapse. In this literature review, we discuss data from treatment with the new drugs at relapse after anti-BCMA therapies, observing an undeniable benefit from the use of drugs directed against GPRC5D., (© 2023. The Author(s).)

Objective: We investigate safety and efficacy in common clinical practice of the combination of carfilzomib and dexamethasone (Kd56) approved for the ENDEAVOR trial for the treatment of relapsed or refractory multiple myeloma., Methods: We retro-prospective analyzed 75 patients in three centers in Tuscany, 48 of whom had a clinically relevant comorbidity and 50 of whom were older than 65 years, treated with a median use in the fourth line of therapy. We assessed the efficacy based on the International Myeloma Working Group criteria., Results: The overall response rate was 60%. Median PFS was 10 months in the general cohort; in patients treated for more than 1 cycle of therapy PFS was 12 months. Quality of response to Kd56 treatment was found to positively impact PFS. Refractory status to previous line of therapy or to lenalidomide or an history of exposure to pomalidomide, seemed to have no impact on survival. We also showed a low adverse events rate, with no neuropathy events, and a relatively small number of cardiovascular events above grade 3 (10%)., Conclusion: Kd56 is an effective and well tolerated regimen in highly pretreated and elderly patients with a good safety profile., (© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Systemic amyloidosis arises from monoclonal CD38+ plasma cells that produce misfolded immunoglobulin light chains, which form amyloid fibrils that are deposited into different tissues, leading to organ damage. Daratumumab is a human IgG/k monoclonal antibody that targets CD38, a glycoprotein uniformly expressed on human plasma cells. Daratumumab has been utilized in recent years with unprecedented responses in multiple myeloma. In patients with relapsed or refractory AL amyloidosis, daratumumab has shown promising efficacy in terms of hematologic responses and improvement in organ function. Here, we report real-life treatment with Daratumumab in 33 AL amyloidosis patients treated within the Regional Tuscan Myeloma network at 5 centers with associated MGUS or SMM ( n = 15) or symptomatic MM ( n = 18). Patients were treated at relapsed/refractory disease stages ( n = 29) with a median of one previous line of therapy or at diagnosis ( n = 4). Daratumumab showed good efficacy, representing 60% of good hematological responses and 50% of organ responses in a real-life population of patients with an acceptable toxicity profile.

Amyloidosis is a rare disease that is often seen in conjunction with multiple myeloma (MM). Its damage varies depending on the anatomical site affected; however, it is believed that many cases of amyloidosis are misrecognized due to the fact that its signs and symptoms are nonspecific. Joint amyloidosis, in particular, may be confused with degenerative or autoimmune diseases. When it is associated with MM, it can significantly precede the diagnosis of the latter. We describe a case report of a woman of Nigerian heritage diagnosed with MM with widespread joint manifestations compatible with a diagnosis of amyloidosis, which had preceded the diagnosis of MM and benefited from MM treatment. Faced with the suspicion of amyloidosis, if confirmed, this can be used to anticipate the diagnosis of MM, and at a more advanced stage, it can benefit from the treatment of the MM.

Background and Objectives : The treatment of Myeloma after the second relapse is still challenging. The aim of the study was to investigate the outcomes of the POM-DEX regimen in real clinical practice. Materials and Methods: We retrospectively and prospectively analyzed 121 patients with MM treated with POM-DEX in three Italian sites in Tuscany. We assessed the efficacy based on IMWG Uniform Response Criteria in 106 patients who had received at least two courses of the POM-DEX regimen. The median time from diagnosis to use of POM-DEX was 65 months. POM-DEX median use was in the fourth-line therapy. 63.6% were exposed to lenalidomide or thalidomide, 40.5% to bortezomib or carfilzomib or ixazomib, 5.8% to mAbs in the immediately preceding line of therapy. Results: ORR was 43.4%. Median PFS and OS were 8.5 and 14 months. Eighty-nine patients received more than two courses: their median PFS and OS were 11 and 16 months. When used as the third line of therapy, median PFS and OS were 9 and 20 months and, when patients received POM-DEX for more than two courses, median PFS and OS were 14.5 and 22.5 months. Conclusions: POM-DEX is effective in RRMM, regardless of the latest exposure to IMiDs, PIs, and mAbs in the previous line of therapy.

Introduction: Currently, the regimen with bortezomib plus melphalan and prednisone (VMP) is a standard treatment for multiple myeloma and it is recommended as the first-line therapy for patients with multiple myeloma (MM) ineligible for high-dose chemotherapy with autologous stem-cell transplantation. Objectives: Participants of the clinical trial are highly selected populations; therefore, the aim of this study was to present observations from real practice that can provide important information for practitioners and to investigate clinical outcomes of VMP regimen in elderly patients with newly diagnosed MM. Patients and Methods: We retrospectively analyzed the data on the efficacy and survival parameters, such as overall survival (OS) and event-free survival (EFS), with attention to the effect of gender, age and International Staging System (ISS) stage, of VMP regimen in 164 patients with newly diagnosed MM not eligible for high-dose chemotherapy with autologous stem-cell transplantation (median age, 75 years; range, 60-86 years). Results: Patients aged 75 years or older constituted 50.6% of the study cohort. Frail patients were 10.36%, according to the clinical frailty scale of geriatric assessment (GA). A total of 1203 courses of VMP regimen (mainly VMP 1-29, 99.16 %) were administered. The median cumulative delivered dose of bortezomib was 46.8 mg/m2. The overall response rate (ORR), including all patients with a partial response or better, was 81.7% and the complete response rate (CRR) was 10.36 %. After a median 38.51 months of follow-up, the median overall survival (OS) was 34.33 months; the median event-free survival (EFS) after VMP and second-line therapy (mainly Rd, 56.31%) were 18.51 and 10.75 months, respectively. In the subgroup of patients with 75 years or older the median OS was 29.76 months; the median EFS after first and second-line therapy were 17.76 and 8.93 months, respectively. The hazard ratio for OS was 2.276 ( p -value 0.046) and for EFS was 1.507 ( p -value 0.055) for the ISS stage II and III group. Age and gender were not negative predictors of survival. Conclusions: VMP treatment is highly effective in the first-line therapy of elderly patients with multiple myeloma ineligible for HDT with auto-SCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Buda, Del Giudice, Antonioli, Ghio, Orciuolo, Morganti, Martini, Staderini, Galimberti and Petrini.)

Psychosocial constructs have been used to predict colorectal cancer screening and are frequently targeted as intermediate outcomes in behavioral intervention studies. Few studies have conducted analyses to adequately test construct validity. The psychometric analyses undertaken with U.S. populations of 16 theory-based, colorectal cancer screening items designed to measure five factors (salience-coherence, cancer worries, perceived susceptibility, response efficacy, and social influence) are an exception. The current investigation replicates previous work by examining factor validity and invariance in a random sample of Ontario, Canada residents. A survey instrument was administered to 1,013 Ontario male (49%) and female (51%) residents randomly selected by the Canada Survey Sample. Single-group confirmatory factor analyses (CFA) assessed data fit to the proposed five-factor model for males and females separately, and then a multigroup CFA evaluated if the factor structure was invariant for men and women. The five-factor model provided good fit for both males and females. Tests for factorial invariance between sexes, however, found mixed results. chi2 difference test was significant (P = 0.025); however, DeltaRMSEA = 0.0001. Factor loadings were similar by sex except for two social influence items, with item frequency distributions suggesting an extreme response style, in females, on these items. Overall, the single-group and multigroup CFA results support factorial validity and partial invariance of the five-factor model first identified in the U.S. populations. The items can be used to evaluate and compare psychosocial correlates across U.S. and Canadian samples. Additional research is needed to show invariance for other ethnocultural and national subgroups.