Search

Extramedullary plasmacytoma (EMP) and solitary bone plasmacytoma (SBP) represent a disease continuum through a multistage process of cell differentiation, survival, proliferation, and dissemination, strictly related to multiple myeloma (MM), the second most common hematological malignancy. Herein, we report two cases of recurrent oral plasmacytoma progressed to MM, in which the first clinical sign of a more widespread disease was limited to the mouth. Based on our experience, we recommend a strict workup for the differential diagnosis between EMP, SBP, and MM for patients with oral plasmacytoma, including radiological exam of the skeleton, magnetic resonance imaging (MRI) of the bone, and positive emission tomography (FDG-PET). MRI and possibly PET can all be used to more sensitively detect EM plasmacytoma sites.

Limited data suggest that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) may have a role in diagnosing infection. Here we present two cases of lymphoma patients in complete response (CR) who presented during follow-up dry cough and fever. Physical examination and serum evaluations were negative for lymphoma while whole body FDG-PET showed lung uptake which posed a differential diagnosis between relapse of lymphoma and an atypical pneumonia due to persistent lymphopenia. In both cases, cytology examination of sputum suggested Pneumocystis Jiroveci pneumonia (PJP). After appropriate antibiotic treatment, the follow-up examination showed complete resolution of the lung changes revealed by FDG-PET. False-positive results on FDG-PET were supposed to be due to the high uptake of FDG in non-neoplastic inflammatory cellular elements such as macrophages and lymphocytes. Our findings suggest that in cases of FDG-PET positive images in immunocompromised patients with previous hematologic disease, caution must be used, and differential diagnosis might include infections such as PJP in addition to relapse of disease.

Background: Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS)., Materials and Methods: This retrospective analysis included 247 Dara-R MM patients treated with EloPd. All patients were also refractory to lenalidomide, with 51.4% to a proteasome inhibitor, thus classified as triple-class refractory (TCR). Survival risk-scoring systems for PFS (progression-free risk score-PRS DaraR ) and OS (survival risk score-SRS DaraR ) were developed to stratify patients based on their risk profiles., Results: The overall response rate was 52.6%, with a median PFS and OS of 6.6 and 17.0 months, respectively. The International Staging System (ISS) stages II and III, low hemoglobin (Hb) levels, the last therapy being daratumumab, and symptomatic relapse were identified as significant independent predictors of shorter PFS in multivariable analysis. In addition to advanced ISS stages, low Hb levels (<10.6 g/dl), symptomatic relapse, and refractory disease exhibited an independent negative impact on OS. Importantly, no significant differences in both PFS and OS were observed between TCR and non-TCR patients. Based on these multivariable analyses, we developed PRS DaraR and SRS DaraR according to the magnitude of the hazard ratio. In PRS DaraR , 10.1% were low-risk, 41.3% intermediate, 43.3% high, and 5.3% very high-risk. The 12-month PFS probabilities were 86.3% (low), 67.6% (intermediate), 52.9% (high), and 31.8% (very high). For SRS DaraR , 6.1% were low-risk, 47.8% intermediate, 19.4% high, and 26.7% very high. The 12-month OS probabilities were 90.9% (low), 75.7% (intermediate), 55.9% (high), and 32.6% (very high)., Conclusions: This study supports EloPd as an effective treatment option in Dara-R MM patients, providing valuable disease control and acting as a potential bridge to newer therapies, such as CAR-T and bispecific antibodies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current therapeutic approaches are unsatisfactory. The role of new molecules and in particular of monoclonal antibodies is under investigation. To determine whether daratumumab-based regimens are effective for myeloma with EMP, we report herein an initial multicenter observational analysis of 102 myeloma patients with EMP (n = 10) and PP (n = 25) at diagnosis and EMP (n = 28) and PP (n = 39) at relapse, treated with daratumumab-based regimens at 11 Haematological Centers in Italy.EMP and PP at diagnosis were associated with higher biochemical (90% vs. 96%, respectively) and instrumental ORR (86% vs. 83.3%, respectively), while at relapse, biochemical (74% vs. 73%) and instrumental (53% vs. 59%) ORR were lower. Median OS was inferior in EMP patients compared with patients with PP both at diagnosis (21.0 months vs. NR) (p = 0.005) and at relapse (32.0 vs. 40.0 months) (p = 0.428), although, during relapse, there was no statistically significant difference between the two groups. Surprisingly, at diagnosis, median TTP and median TTNT were not reached either in EMP patients or PP patients and during relapse there were no statistically significant differences in terms of median TTP (20 months for two groups), and median TTNT (24 months for PP patients vs. 22 months for EMP patients) between the two groups. Median TTR was 1 month in all populations.These promising results were documented even in the absence of local radiotherapy and in transplant-ineligible patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: No potential conflict of interest was reported by the author(s)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Respiratory syncytial virus is a leading cause of respiratory hospitalisations in infants. This systematic review (registration number: CRD42021248309) aims to synthesise the available evidence on Respiratory Syncytial Virus-related hospitalisations among children aged 0 to 6 years in Italy., Methods: The literature search was conducted on PubMed, Embase, Scopus, and International HTA, covering the period from January 2000 to July 2022, with a focus on studies that reported information on Respiratory Syncytial Virus-associated hospitalisation in children aged 0-6 years in Italy., Results: Eight articles were included after screening 20,845 records. These retrospective studies reported that most hospitalisations were among those <1 year (71.5%-88.8%), infants aged <1 year were also at higher risk of hospitalisation in intensive care unit. Respiratory Syncytial Virus infections typically peaked December-February, with an atypical early start in August 2021. Subtype analysis showed alternating prevalence of Respiratory Syncytial Virus-A and Respiratory Syncytial Virus-B across different seasons. Coinfections were not uncommon (1.1%-37.4%), with rhinovirus and bocavirus being the most frequent., Conclusions: All infants at their first Respiratory Syncytial Virus season showed an increased risk of severe infection and hospitalisation, regardless of the gestational age at birth, compared to older participants. This systematic review will enrich the understanding about Respiratory Syncytial Virus disease and help support decisions regarding prevention efforts in Italy.

Not available.

Somatic mutations of hematopoietic cells in the peripheral blood of normal individuals refer to clonal hematopoiesis of indeterminate potential (CHIP), which is associated with a 0.5-1% risk of progression to hematological malignancies and cardiovascular diseases. CHIP has also been reported in Multiple Myeloma (MM) patients, but its biological relevance remains to be elucidated. In this study, high-depth targeted sequencing of peripheral blood from 76 NDMM patients revealed CHIP in 46% of them, with a variant allele frequency (VAF) ranging from ~ 1 to 34%. The most frequently mutated gene was DNMT3A, followed by TET2. More aggressive disease features were observed among CHIP carriers, who also exhibited higher proportion of high-risk stages (ISS and R-ISS 3) compared to controls. Longitudinal analyses at diagnosis and during follow-up showed a slight increase of VAFs (p = 0.058) for epigenetic (DNMT3A, TET2, and ASXL1) and DNA repair genes (TP53; p = 0.0123). A more stable frequency was observed among other genes, suggesting different temporal dynamics of CH clones. Adverse clinical outcomes, in term of overall and progression-free survivals, were observed in CHIP carriers. These patients also exhibited weakened immune T-cells and enhanced frailty, predicting greater toxicity and consequently shorter event-free survival. Finally, correlation analysis identified platelets count as biomarker for higher VAF among CHIP carriers, regardless of the specific variant. Overall, our study highlights specific biological and clinical features, paving the way for the development of tailored strategies for MM patients carrying CHIP., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis has not been completely clarified, and it is generally associated with high-risk cytogenetics (HRCAs). In order to emphasize the clinical and biochemical complexity of this disease, we have decided to describe the case of a patient affected by relapsed-refractory (RR) EMD, which presented as para-osseous plasmacytoma with a bi-phenotypical immunoglobulin (Ig) component and lately relapsed as soft-tissue plasmacytoma with a total immunophenotype switch. We have also hypothesized a correlation between Ig patterns and prognosis and suggested the possible inclusion of these biochemical features in the general risk assessment.

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab., (© 2024 John Wiley & Sons Ltd.)

Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease., (© 2024 John Wiley & Sons Ltd.)

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42-86 years), ECOG performance status was ≥1 in 45% of patients. Overall, a clinical benefit was obtained in 36 out of 74 evaluable patients (49%), with 43%, 28%, and 13.5% achieving at least partial response, very good partial response, and complete response, respectively. After a median follow-up of 12 months (range 6-21 months), median duration of response, progression-free survival (PFS), and overall survival (OS) were 14, 5.5, and 12 months, respectively. Age >70 years, good performance status and response were associated with longer PFS and OS. Keratopathy occurred in 58% of patients (G3 2.5%), corneal symptoms in 32% (G3 1.2%) and a reduction in visual acuity in 14%. Grade 3 thrombocytopenia occurred in 9% of patients. Only 3% of patients discontinued belantamab mafodotin because of side effects. This real-life study demonstrated significant and durable responses of belantamab in TCR-MM patients with four prior LOTs, otherwise ineligible for novel immunotherapies., Competing Interests: Francesca Fazio ‐ advisory board: GSK; honoraria: Amgen, Takeda, Janssen‐Cilag, GSK, BeiGENE, and Sanofi Maria Teresa Petrucci ‐ honoraria: Janssen‐Cilag, Celgene‐BMS, Amgen, Sanofi, GSK, and Takeda; advisory boards: Janssen‐Cilag, Celgene‐BMS, Amgen, Sanofi, GSK, Takeda, Roche, Oncopeptides, Pfizer, Menarini, and AbbVie; support for attending meetings and/or travel: Janssen‐Cilag, Celgene‐BMS, Amgen, Sanofi, and Takeda. Laura Corvatta ‐ honoraria: BMS, Janssen, and GSK. Alfonso Piciocchi ‐ no conflicts of interest. Roberta Della Pepa ‐ advisory boards: Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda. Paola Tacchetti ‐ honoraria: Amgen, Bristol‐Myers Squibb/Celgene, Janssen, Takeda, AbbVie, Sanofi, GlaxoSmithKline, and Pfizer. Maurizio Musso ‐ no COI. Renato Zambello ‐ advisory boards: Roche, Janssen, Bristol Meier Squibb, Sanofi, Amgen, and GSK. Angelo Belotti ‐ advisory boards: Amgen, GSK, Janssen, Takeda, and Pfizer. Sara Bringhen ‐ speakers’ bureaus: Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and AbbVie; advisory boards: Bristol Myers Squibb, Janssen, Takeda, Pfizer, Stemline Therapeutics, and Oncopeptides; consultancy fees: Sanofi. Elisabetta Antonioli ‐ advisory boards: Janssen‐Cilag, Celgene‐BMS, Amgen, Sanofi, GSK, Takeda, and Pfizer; support for attending meetings and/or travel: Janssen‐Cilag and Sanofi. Concetta Conticello ‐ honoraria: Takeda, Amgen, Janssen, GSK, BMS, and Sanofi. Nicola Di Renzo ‐ honoraria: Janssen, Bristol Myers Squibb, Gilead, Jazz, and AbbVie; advisory boards: Janssen, Bristol Myers Squibb, Jazz, and AbbVie. Valerio De Stefano ‐ advisory boards for: AOP Health, Argenx, Bristol Myers Squibb, Glaxo Smith Kline, Grifols, Novartis, SOBI, and Takeda; speaker fees from Abbvie, Alexion, Amgen, Bristol Myers Squibb, Grifols, Leo Pharma, Novartis, Novo Nordisk, Sanofi, and Takeda; research grant from Alexion. Pellegrino Musto ‐ honoraria: Abbvie, Alexion, Amgen, Astellas, Astra‐Zeneca, Bei‐Gene, Bristol‐Myers Squibb/Celgene, Gilead, Glaxo‐Smith‐Kline, Grifols, Incyte, Janssen, Jazz, Novartis, Pfizer, Roche, Sanofi, Sobi, and Takeda. Barbara Gamberi ‐ honoraria: Amgen, Bristol Myers Squibb, Janssen, and Takeda; advisory boards: Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and Takeda. Daniele Derudas ‐ no conflicts of interest. Mario Boccadoro ‐ honoraria: Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and AbbVie; advisory boards: Janssen and GlaxoSmithKline; research funding: Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Mundipharma. Massimo Offidani ‐ honoraria and advisory boards: Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda. Sonia Morè ‐ honoraria: BMS, Janssen, and GSK., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Respiratory syncytial virus (RSV) is a frequent cause of acute lower respiratory infection in children, imposing a substantial economic burden on healthcare systems. This systematic review aimed to assess the economic burden and healthcare utilisation of RSV in children aged 0-59 months in Italy., Study Design: Systematic review., Methods: A systematic search of PubMed, Embase, Scopus, and the International HTA Database, including studies published in English or Italian, was conducted between January 2000 and July 2022. Inclusion criteria required studies to be conducted in Italy and provide data on the economic costs and healthcare resource utilisation related to RSV infections., Results: Out of 20,845 records screened, 18 articles met the inclusion criteria. Only one study provided comprehensive data on RSV disease costs, including hospitalisation, diagnostic tests, and medical procedures for infants with RSV-bronchiolitis. The mean cost per inpatient was higher for RSV-positive children (€5753.43 ± €2041.62) than that for RSV-negative children. Additionally, five studies reported a median length of hospital stay of 5 days for RSV-infected children, and four studies indicated a higher frequency of intensive care unit admissions for RSV-infected children than for those with other viral infections., Conclusions: This is the first systematic review to examine the economic burden and healthcare utilisation of RSV in children aged 0-59 months in Italy. While limited data were available, the findings underscore the urgency to conduct further research and gather additional evidence on the costs and healthcare resource utilisation associated with RSV infections. Such efforts are essential for informing the development of effective prevention strategies for paediatric RSV infections in Italy., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival was 7 months, which was shorter than that observed in ELOQUENT-3, probably because of the different clinical characteristics of the two cohorts. Interestingly, International Staging System stage III disease was associated with worse progression-free survival (hazard ratio=2.55). Finally, the median overall survival of our series was shorter than that observed in the ELOQUENT-3 trial (17.5 vs. 29.8 months). In conclusion, our real-world study confirms that EloPd is a safe and possible therapeutic choice for patients with RRMM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Although the therapeutic landscape for multiple myeloma (MM) has expanded, the disease always tends to relapse. In an attempt to obtain deep and durable responses, each relapse requires the use of a new strategy. In recent years, new treatment options have emerged, even for heavily treated patients. Novel, well-tolerated, and highly effective therapies in the relapsed/refractory (RRMM) setting currently represent a real hope. Belantamab mafodotin (BLENREP™) is a first-in-class monoclonal antibody-drug conjugate whose target is B-cell maturation antigen conjugated to the cytotoxic microtubule inhibitor monomethyl auristatin F. Here, we present two cases of heavily pre-treated RRMM patients that were favorably treated with belantamab mafodotin, obtaining at least a partial response. Treatment was well tolerated and is ongoing. This is a rare report on real life clinical use of belantamab mafodotin outside of controlled clinical trials and provides information on efficacy and safety of this anti-myeloma new class of drugs., (© 2023 S. Karger AG, Basel.)

Background: Managing SARS-CoV-2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab-cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real-life data in a heterogeneous cohort are few., Methods: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab-cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch-and-wait strategy, followed in our center, during a median follow-up of 249 (45-325) days., Results: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment-related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab-cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti-CD20 monoclonal antibodies and B-non-Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred., Conclusion: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity., (© 2023 American Cancer Society.)

Background: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid β-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists., Patients and Methods: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022., Results: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm 3 ) in 24 (5.5%). Of 600 MGUS patients tested for acid β-glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity., Conclusions: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)