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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. [ABSTRACT FROM AUTHOR]

The reliability and safety of front‐line ultrasonography guided core needle biopsy (UG‐CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG‐CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG‐CNB from four Italian clinical units that routinely utilized 16‐gauge diameter modified Menghini needle under power‐Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG‐CNB in untreated patients over a 12‐year period. Overall, 1000 (superficial target, n = 750; deep‐seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B‐cell non‐Hodgkin lymphoma [aBc‐NHL], 309 cases; indolent B‐cell [iBc]‐NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T‐cell [NPTC]‐NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non‐malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro‐histological sampling was 97% (95% confidence interval: 95%–98%) for the series. The sensitivity of UG‐CNB for the detection of aBc‐NHL was 100%, for iBc‐NHL 95%, for HL 93%, and for NPTC‐NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy‐related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG‐CNB as mini‐invasive diagnostic procedure is effective with minimal risk for the patient. [ABSTRACT FROM AUTHOR]

Introduction: hematological malignancies are associated with an increased thrombotic risk compared to solid tumors. Multiple myeloma (MM) is a hematological neoplastic disease with strong thromboembolic repercussions. In these patients the venous thromboembolism may occur during the first months of treatment with immunomodulatory drugs (IMiDs), in combination with high-dose of dexamethasone. Although IMiDs therapy improves the clinical outcome, a concomitant increase of thromboembolic manifestations are observed. Rotational thromboelastometry, provides information on the clot formation, its stabilization and dissolution, reflecting in vivo patient's hemostasis. The aim of the study was to investigate the dynamic state of clot formation, through the evaluation of research parameters, in addition to standard ones, to best evaluate the thrombotic risk in these patients. Methods: thirty-four MM patients and thirty-five controls were unrolled from Hematology Department of the University Hospital Federico II of Naples, Italy. To evaluate the coagulation's dynamics status, we investigated EXTEM, INTEM and FIBTEM assays, through both standard (CT, CFT, MCF, α-angle) and research (MAXV, MAXVt, AUC) parameters, using Rotational Thromboelastometry. Results: among the research parameters, we observed statistical significance differences between controls and patients for EXTEM (MAXV: p=0.010; MAXVt: p=0.010), for INTEM (MAXV:10 p=0.005; MAXVt: p=0.005) and for FIBTEM (MAXV: p<0.001; AUC: p<0.001) tests. Discussion: to the best of our knowledge, this is an original study showing that research parameters can give an additional contribution to the interpretation of the hypercoagulability state in MM patients, bringing to light patients who could be at higher thrombotic risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Central vein catheter (CVC) insertion is a main risk factor for deep vein thrombosis and blood stream infection in patients undergoing induction chemotherapy for acute leukemia. The decision of the treating physician to catheterize the basilica/brachial vein site as the frontline central vascular access has an important effect in minimizing morbidity and likely health care costs related to CVC complications in hematologic patients with severe and prolonged neutropenia. The basilic/brachial (BBV), internal jugular (IJV), and subclavian veins (SCV) are commonly used as central venous catheter (CVC) sites. A BBV approach [peripherally inserted central catheter (PICC)] is increasingly used for short- to intermediate-term CVCs for acute leukemias undergoing cytotoxic intensive regimens. In this retrospective study, the catheterization of the BBV, IJV, and SCV in patients with previously untreated acute leukemia was assessed. The primary outcome was the composite incidence of catheter-related symptomatic deep-vein thrombosis (sDVT) and bloodstream infection (BSI) from catheterization up to 30 days later. In a 10-year period, 336 CVC were inserted in the BBV (n = 115), IJV (n = 111), and SCV (n = 110) in 336 patients suffering from AML (n = 201) and ALL (n = 135) and undergoing induction chemotherapy. The primary outcome events were 8, 20, and 27 in the BBV, SCV and IJV cohorts (2.6, 6.9, and 9.6 per 1000 catheter-days, respectively; p = 0.002). The primary outcome risk was significantly higher in the IJV-cohort than in the BBV-cohort (HR, 3.6; 95% CI, 1.6 to 7.9; p = 0.001) and in the SCV-cohort than in the BBV-cohort (HR, 2.6; 95% CI, 1.2 to 5.9; p = 0.02). PICC was a valid CVC for the induction chemotherapy of acute leukemia for the lowest risk of sDVT and BSI. [ABSTRACT FROM AUTHOR]

Simple Summary: Our retrospective collection from the database registry of the Hematology Unit of the Federico II University Medical School of Naples (Italy) of all patients referring to our center (from 1 January 2009 to 31 January 2019) for lymph node biopsy-proven lymphoma and one or more distinct splenic lesions, visible at baseline ultrasonographic scans and submitted to CEUS, could be a great asset in the diagnostic approach for splenic lymphoma. For the first time, based on a robust sample size of 260 nodules (with final diagnoses uniformly controlled by clinical laboratory imaging follow-up, in the cases not directly biopsy-proven) we showed that CEUS can achieve the diagnosis of splenic malignant lymphoma with excellent accuracy. Contrast-enhanced ultrasonography (CEUS) use for detecting lymphoma in the spleen was questioned because of the risk of its inadequate diagnostic accuracy. The aim of the present study was to validate CEUS exam for the identification of spleen involvement by lymphoma in patients at risk. A total of 260 nodules from the spleens of 77 patients with lymph node biopsy-proven non-Hodgkin lymphoma (NHL; n = 44) or Hodgkin lymphoma (HL; n = 33) at staging (n = 56) or follow-up (n = 21) were collected in a hematology Italian center and retrospectively analyzed. Nodules were classified as malignant lymphoma if ≥0.5 cm (long axis) with arterial phase isoen-hancement and early (onset <60 s after contrast agent injection) wash-out of marked (≤120 s after contrast agent injection) degree. Other perfusional combinations at CEUS scans qualified lesions as benign or inconclusive. Diagnostic reference standard was clinical laboratory imaging monitoring for 230 nodules, and/or histology for 30 nodules. The median nodule size was 1.5 cm (range 0.5–7 cm). According to the reference standard, 204 (78%) nodules were lymphomas (aggressive-NHL (a-NHL), 122; classic-HL (c-HL), 65; indolent (i)-NHL, 17) and 56 (22%) were benign (inflammation, infection, and/or mesenchymal) lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of CEUS for detecting lymphoma in the spleen were 95%, 100%, 100%, 85%, and 96%, respectively. Marked wash-out range of 55–90 s (median, 74 s), 92–120 s (median, 100 s), and 101–120 s (median, 114.5 s) was 100%, 96.6%, and 77% predictive of a-NHL, c-HL, and i-NHL splenic nodular infiltration, respectively. The CEUS perfusional pattern of arterial phase isoenhancement with early wash-out of marked degree was highly accurate for the detection of lymphomatous invasion of spleen in patients at risk, enabling its use for a confident non-invasive diagnosis. [ABSTRACT FROM AUTHOR]

By contrast, the sensitivity rate for lymph node malignant status was 98-8% (95% CI 95-9-99-9%) for PDUS-guided CNB with a false-negative rate of 1-1% (two of 174 patients with lymph nodes positive for malignancy were not identified). The authors emphasised the value of lymph node excisional biopsy as the "gold standard", with the need of a tight partnership with surgical colleagues as part of a multidisciplinary team that can facilitate the surgery excisional biopsy decision-making process. Randomized comparison of power Doppler ultrasound-directed excisional biopsy with standard excisional biopsy for the characterization of lymphadenopathies in patients with suspected lymphoma. [Extracted from the article]

Objectives: To assess the prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis in ocular adnexa lymphoma (OAL) determined by molecular testing in different countries and the potential association of Chlamydia infection with mucosa-associated lymphoid tissue (MALT) histotype by performing a systematic review and meta-analysis.Methods: Electronic databases were searched for studies assessing the presence of Chlamydia in OAL. Pooled prevalence of the three Chlamydia species was calculated in each country. An odds ratio was calculated for the association between Chlamydia and MALT histotype, with a significant P < .05.Results: Thirty-seven studies with 1,188 OALs were included. Pooled prevalence of C psittaci, C pneumoniae, and C trachomatis by country was done. Chlamydia infection was significantly associated with MALT histotype (odds ratio, 2.183; P = .027).Conclusions: The involvement of C psittaci in OAL is highly variable, with the highest prevalence in Italy and Korea. Chlamydia is associated with MALT histotype. [ABSTRACT FROM AUTHOR]

Efficacy and infection morbidity of front-line immuno-chemotherapy in follicular lymphoma. Thus, during the 3-year infection follow-up, bendamustine-based regimens led to a high rate of patients experiencing any grade of infection and a high number of infection-related admissions. Primary vigorous anti-infective prophylaxis to reduce the rate of infections and related chemotherapy disruptions in patients with untreated follicular lymphoma. [Extracted from the article]

Neutropenic enterocolitis ( NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia ( AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively ( P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality ( P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [ OR]: 0.109; 95% confidence interval [ CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome ( OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset. [ABSTRACT FROM AUTHOR]

Background Longitudinal strain is an early marker of left ventricular ( LV) dysfunction in several cardiac diseases. Our aim was to differentiate cardiac amyloidosis ( CA) at diagnosis from hypertensive LV hypertrophy ( LVH) by analysis of longitudinal myocardial deformation. Methods Thirty healthy controls (C), 30 newly diagnosed, never treated hypertensives with LVH ( H- LVH), and 33 patients with CA at diagnosis underwent echo Doppler including speckle tracking-based automated function imaging ( AFI). Averaged peak systolic global longitudinal strain ( GLS, 18 segments) and basal, middle, and apical longitudinal strain ( BLS, MLS, and ALS, respectively, six segments each) were calculated. Results Left ventricular mass index, relative wall thickness, and ejection fraction did not differ between H- LVH and CA. E/ e′ ratio was higher in CA than in H- LVH (P<.001) and C (P<.0001). GLS was lower in CA than in C (P<.0001), without difference with H- LVH. ALS did not differ among the three groups, MLS was significantly lower in both CA and H- LVH than in C but BLS was lower in CA compared to both H- LVH and C (both P<.0001). In the pooled population, E/ e′ was independently associated with BLS (β=−0.54, P<.0001). At receiver operating curve analysis, CA was predicted by BLS≤−11.3% (sensitivity=63.3%, specificity=100%) and E/ e′≥12.3 (sensitivity=69.7%, specificity=83.3%). The best AUC (=0.819) was obtained by the combination E/ e′+ BLS. Conclusions Our findings highlight a real difference of E/ e′ ratio and longitudinal strain of LV basal segments between hypertensive LVH and CA, which could be used to differentiate the two diseases. [ABSTRACT FROM AUTHOR]

This letter to the editor remarks on the article by Cheng et al., which reported results of a retrospective study that assessed 5‐year progression‐free and overall survival (OS) of 98 patients with hepatitis B surface antigen–seropositive patients receiving R‐CHOP‐21 as remission induction for diffuse large B‐cell lymphoma. [ABSTRACT FROM AUTHOR]

Fine-needle cytology (FNC) is a useful diagnostic tool in the first line evaluation of lymphadenopathy of unknown aetiology. Nevertheless, considering the large number of conditions presenting as lymphadenopathy, lymph node cytology represents a challenging scenario. Recently, an expert panel published the proposal of the Sydney system for performing classification and reporting of lymph node cytopathology; the aim of the present study was to evaluate the applicability of this system. Thus, 300 lymph node FNCs performed over 1 year were reviewed and categorized according to the Sydney system classification. Overall, n = 20 cases (6.7%) were categorized as L1-inadequate/non-diagnostic; n = 104 (34.7%) as benign (L2); n = 25 (8.3%) as atypical (L3); n = 13 (4.3%) as suspicious (L4), and n = 138 (46%) as malignant (L5). FNC diagnoses were correlated with histopathologic and clinical follow-up to assess the diagnostic accuracy and the risk of malignancy (ROM) for each diagnostic category. Statistical analysis showed the following results: sensitivity 98.47%, specificity 95.33%, positive predictive value 96.27%, negative predictive value 98.08%, and accuracy 97.06%. The ROM was 50% for the category L1, 1.92% for L2, 58.3% for L3, and 100% for L4 and L5. In conclusion, FNC coupled with ancillary techniques ensures satisfactory diagnostic accuracy and the implementation of the Sydney system may improve the practice of cytopathologists. [ABSTRACT FROM AUTHOR]

ABSTRACT Isatuximab, a novel anti‐CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa‐Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real‐world efficacy and safety are poorly reported. In this Italian multicenter real‐life observational retrospective study, efficacy and safety of the Isa‐Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1‐year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa‐Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1‐year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa‐Kd as an effective treatment option for RRMM with a manageable safety profile even in real‐life settings. [ABSTRACT FROM AUTHOR]

Simple Summary: The current literature on NLPHL therapy is scarce due to the disease rarity. Our study aims to focus on the management and treatment strategies of NLPHL based on risk stratification. This paper contributes to the current literature, based mainly on retrospective studies and on small cohort studies, confirming the benefit of Rituximab for patients with NLPHL, in particular for those with advanced disease. We hope that our results can be confirmed by larger cohort studies from the research community. Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy. [ABSTRACT FROM AUTHOR]

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.)

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.

Belantamab-mafodotin is an innovative and selective treatment for multi-refractory/relapsed multiple myeloma (MM) patients; however, available real-life experiences on efficacy and safety are limited. In this real-world multicentric retrospective study, we enrolled 28 MM patients treated in four Hematology units of Campania region, Italy, who received a median of six treatment lines prior to belantamab-mafodotin. The overall response rate (ORR) was 40% (complete remission, CR, 11%; very good partial remission, VGPR, 11%; and partial remission, PR, 18%), with a median progression-free survival (PFS) and overall survival (OS) of 3 and 8 months, respectively. One of the most frequent drug-related adverse events was keratopathy observed in nine (32%) patients, leading to therapy discontinuation in only three (11%) of them. Moreover, 22 out of 28 total patients who were treated with at least two administrations achieved an ORR of 50% (CR, 14%; VGPR, 14%; and PR, 22%) with a median PFS and OS of 5 and 11 months, respectively. In conclusion, our multicentric study confirmed efficacy and safety of belantamab-mafodotin in triple-refractory MM patients even in the real-life setting., 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 © 2022 Iula, De Novellis, Trastulli, Della Pepa, Fontana, Carobene, Di Perna, D’Ambrosio, Romano, Leone, De Fazio, Fiumarella, Gaeta, Marafioti, Barbato, Palmieri, Rocco, Serio, Califano, Pane, Ferrara, Giudice, Selleri and Catalano.)

We evaluated the impact of liposomal doxorubicin (NPLD) supercharge-containing therapy on interim fluorodeoxyglucose positron emission tomography (interim-FDG-PET) responses in high-risk diffuse large B-cell lymphoma (DLBCL) or classical Hodgkin lymphoma (c-HL). In this phase II study (2016-2021), 81 adult patients with advanced-stage DLBCL (n = 53) and c-HL (n = 28) received front-line treatment with R-COMP-dose-intensified (DI) and MBVD-DI. R-COMP-DI consisted of 70 mg/m 2 of NPLD plus standard rituximab, cyclophosphamide, vincristine and prednisone for three cycles (followed by three cycles with NPLD de-escalated at 50 mg/m 2 ); MBVD-DI consisted of 35 mg/m 2 of NPLD plus standard bleomycin, vinblastine and dacarbazine for two cycles (followed by four cycles with NPLD de-escalated at 25 mg/m 2 ). Patients underwent R-COMP-DI and MBVD-DI with a median dose intensity of 91% and 94% respectively. At interim-FDG-PET, 72/81 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalisation. At a median 21-months of follow-up, the progression-free survival of the entire population was 77.3% (95% confidence interval 68%-88%). Our data suggest that the NPLD supercharge-driven strategy in high-risk DLBCL/c-HL may be a promising option to test in phase III trials, for improving negative interim-FDG-PET cases incidence., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The lack of validation and standardization represents the main drawback for a clear role of whole-body diffusion weighted imaging (WB-DWI) for prediction and assessment of treatment response in Hodgkin's lymphoma (HL). We explored the reliability of an automatic approach based on the WB-DWI technique for prediction and assessment of response to treatment in patients with HL. The study included 20 HL patients, who had whole-body positron emission tomography (PET)/ magnetic resonance Imaging (MRI) performed before, during and after chemotherapy. Using the syngo.via MR Total Tumor Load tool, we automatically extracted values of diffusion volume (DV) and its associated histogram features by WB-DWI images, and evaluated their utility in predicting and assessing interim and end-of-treatment (EOT) response. The Mann-Whitney test followed by receiver operator characteristic (ROC) analysis was performed between features and their inter-time point percentage differences for patients having a complete or partial treatment response, revealing that several WB-DWI associated features allowed for prediction of interim response and both prediction and assessment of EOT response. Our proposed method offers huge advantages in terms of saving time and work, enabling clinicians to draw conclusions relating to HL treatment response in a fully automatic way, and encloses, also, all DWI advantages compared to PET/ computed tomography (CT).

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments., (© 2020 by The American Society of Hematology.)

Background: Longitudinal strain is an early marker of left ventricular (LV) dysfunction in several cardiac diseases. Our aim was to differentiate cardiac amyloidosis (CA) at diagnosis from hypertensive LV hypertrophy (LVH) by analysis of longitudinal myocardial deformation., Methods: Thirty healthy controls (C), 30 newly diagnosed, never treated hypertensives with LVH (H-LVH), and 33 patients with CA at diagnosis underwent echo Doppler including speckle tracking-based automated function imaging (AFI). Averaged peak systolic global longitudinal strain (GLS, 18 segments) and basal, middle, and apical longitudinal strain (BLS, MLS, and ALS, respectively, six segments each) were calculated., Results: Left ventricular mass index, relative wall thickness, and ejection fraction did not differ between H-LVH and CA. E/e' ratio was higher in CA than in H-LVH (P<.001) and C (P<.0001). GLS was lower in CA than in C (P<.0001), without difference with H-LVH. ALS did not differ among the three groups, MLS was significantly lower in both CA and H-LVH than in C but BLS was lower in CA compared to both H-LVH and C (both P<.0001). In the pooled population, E/e' was independently associated with BLS (β=-0.54, P<.0001). At receiver operating curve analysis, CA was predicted by BLS≤-11.3% (sensitivity=63.3%, specificity=100%) and E/e'≥12.3 (sensitivity=69.7%, specificity=83.3%). The best AUC (=0.819) was obtained by the combination E/e'+BLS., Conclusions: Our findings highlight a real difference of E/e' ratio and longitudinal strain of LV basal segments between hypertensive LVH and CA, which could be used to differentiate the two diseases., (© 2016, Wiley Periodicals, Inc.)

Relevance of immune-dysregulation for emergence, dominance and progression of dysplastic clones in myelodysplastic syndromes (MDS) was suggested, but valuable or predictive criteria on this involvement are lacking. We previously reported that reduced T-regulatory cells (Treg) and high CD54 expression on T cell identify a sub-group of patients in whom an immune-pathogenesis might be inferred. Here, we suggest the occurrence of immune-selection of dysplastic clones in a subgroup of MDS patients, with reduced HLA-I and HLA-E on PMN, and propose that an altered immune profile might represent a valuable criterion to classify Low/Int-1 patients on the basis of immune-pathogenesis of MDS., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Paroxysmal Nocturnal Haemoglobinuria (PNH) is due to pathological expansion of a stem progenitor bearing a somatic mutation of PIG-A gene involved in the biosynthesis of the glycosyl-phosphatidyl-inositol (GPI) anchor. Numerous data suggest a role for immune-mediated mechanisms in the selection/expansion of GPI-defective clone. Haemolytic anaemia in PNH is dependent on the effect of complement against GPI-defective red cells. Eculizumab, an anti-C5 monoclonal antibody, is dramatically effective in controlling haemolysis and thrombosis, in reducing fatigue and in improving quality of life of patients. However, this therapy presents new challenges that need to be properly faced. Here, we report the decrease in B, Natural Killer (NK) and regulatory T cells (Treg), an altered cytokine profile of invariant-NKT cells (NKTi) and the increasing of C-X-C chemokine receptor type 4 (CXCR4) receptor in PNH patients before the Eculizumab therapy. Treatment significantly affects some of these alterations: after Eculizumab, the number of B lymphocytes, the cytokine secretion of NKTi and CXCR4 expression on CD8 T cells became similar to healthy donors. No effects were observed on NK and Treg. The amplitude of the GPI-defective compartment remained unchanged., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

The myelodysplastic syndromes (MDS) are clonal disorders characterised by ineffective haematopoiesis with high risk of leukaemia progression. The relevance of immune-dysregulation for emergence, dominance and progression of dysplastic clones has been suggested, but valuable criteria to obtain insight into these connections are lacking. This study showed significant increase of CD8 lymphocytes and mature B cells in the bone marrow (BM) compared to peripheral blood (PB) of low risk MDS patients. Different BM levels of Regulatory T cells (Treg) identified two sub-groups in these patients; only the sub-group with lower Treg percentage showed BM recruitment of CD8 lymphocytes. Different levels of CD54 on BM CD8 cells revealed two sub-groups of Intermediate-1 (Int-1) patients. The sub-group with higher CD54 expression on BM CD8 showed high levels of this molecule also on CD4 cells. BM recruitment of CD8 lymphocytes in the low risk group and/or the presence of high CD54 expression on BM CD8 in Int-1 patients were associated with more pronounced dyserythropoiesis and erythropoietin treatment. Our data shed light on the involvement of immune-mediated mechanisms in Low and Int-1 risk MDS patients and suggest that BM versus PB levels of immune effectors could represent useful criteria for a more homogeneous grouping of MDS patients.