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In elderly patients with high-risk classic Hodgkin lymphoma (c-HL), we evaluated the impact of a new modality treatment without bleomycin, that is, liposomal doxorubicin (NPLD)-based regimen plus consolidation radiotherapy of residual nodal masses (RNMs), on overall survival (OS) and progression free survival (PFS). In this retrospective study (2013-2023) conducted in tertiary hospitals in the bay of Naples (Italy), 50 older adults (median age, 69 years; range, 60-89) with advanced stage c-HL received frontline treatment with MVD ± irradiation. MVD consisted of 25 mg/m 2 of NPLD along with standard Vinblastine and Dacarbazine for a total of 6 cycles (twelve iv administrations, every 2 weeks) followed by radiation of RNMs with size ≥ 2.5 cm at computed tomography. Patients underwent MVD with a median dose intensity of 92%. At 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography (FDG-PET), 90% of patients (45/50 patients; one failed to perform final FDG-PET due to early death) reached complete responses. Altogether, 17 patients (34%) received consolidation radiotherapy of RNMs with Deauville score ≥ 3. At 5-year median follow-up, the OS and PFS of the entire population were 87.5% (95% confidence interval [CI], 78.7-97.4) and 81.6% (95% CI, 71.4-93.2), respectively. Eleven patients (22%) experienced grade ≥ 3 adverse events, and 4 of them required hospitalization. Our data suggest that in older adults with high-risk c-HL NPLD-driven strategy (without bleomycin) plus consolidation radiotherapy (if needed) may be a promising up-front option, to test in phase II clinical trials for improving survival incidence., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

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., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Background: Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a subcutaneous fixed dose of 1800 mg. However, the subcutaneous formulation has only recently been approved in Europe, and real-life data on its safety are still few., Objective: In this multicenter retrospective real-life experience, we provided evidence for the safety of subcutaneous daratumumab in plasma cell disorders., Patients and Methods: A total of 189 patients diagnosed with MM or light chain amyloidosis were included in this retrospective study, and all subjects were daratumumab-naïve. Primary endpoint was safety of subcutaneous daratumumab, especially for infusion-related reaction (IRR) incidence and severity. All patients received premedication with dexamethasone, paracetamol, and antihistamine, with montelukast usage in 85% of cases., Results: Eight patients (4%) experienced IRRs, mainly of grade I-II, and other frequent toxicities were: hematological (thrombocytopenia, 4%; neutropenia, 5%; lymphopenia, 6%) and non-hematological (pneumonia, 4%; diarrhea, 2%; and cytomegalovirus reactivation, 0.5%). In our multicenter retrospective real-life experience, subcutaneous daratumumab was well-tolerated with an excellent safety profile with a very low (4%) IRR incidence, even in frailer MM patients with severe renal impairment or increased body weight., Conclusions: Subcutaneous daratumumab was safe in a real-life setting including patients with severe renal failure and advanced disease. However, further studies on larger and prospective cohorts are required to confirm our real-life observations., (© 2023. The Author(s).)

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.)

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.

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections., (Copyright © 2020. Published by Elsevier B.V.)

Persistent cytopenia due to poor graft function (PoGF) is a relatively common complication which may affect up to 20% of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Treatment options for PoGF remain limited, and reinfusion of additional HSC is often the only way to rescue hematopoiesis. Here we describe a retrospective single-center experience with the thrombopoietin-mimetic agent eltrombopag for the treatment of PoGF. Thirteen patients have received eltrombopag for either PoGF (n = 12) or primary graft failure (n = 1). In the 12 PoGF patients eltrombopag was started at the median time of 79 days after HSCT, due to persistent thrombocytopenia, with concomitant anemia and neutropenia in 7 and 3 patients, respectively. The treatment was started at the dose of 50 mg per day, and eventually increased up to 150 mg in case of lack of response. Hematological response was seen in 7 patients, with 6 complete responses. Hematological responses were seen both in patients with evidence of immune-mediated pathophysiology, and with possible infectious/iatrogenic causes. In responding patients, eltrombopag was discontinued in 6/7 patients without further relapse. These results suggest that eltrombopag is safe and possibly effective in the setting of the treatment of PoGF, and pave the way for future prospective studies.

Background: The incidence of peripherally inserted central catheter (PICC)-related adverse events has been uncertain in the setting of acute myeloid leukemia (AML) compared with the incidence of centrally inserted central catheter (CICC) adverse events., Patients and Methods: We conducted a monocentric, randomized trial of patients with previously untreated AML. Of the 93 patients, 46 had received a PICC and 47 had received a CICC as frontline intravascular device. Thereafter, all patients underwent intensive chemotherapy for hematologic remission induction. The primary endpoint was catheter-related (CR)-bloodstream infection (BSI) and venous thrombosis (VT) rate. The secondary endpoints catheter malfunction, catheter removal, and patient overall survival., Results: The CR-BSI and CR-VT rate in the PICC and CICC groups was 13% and 49%, respectively, with a difference of 36 percentage points (relative risk for CR-BSI or CR-VT, 0.266; P = .0003). The CR-BSI incidence was 1.4 and 7.8 per 1000 catheters daily in the PICC and CICC groups, respectively. Among the CR thromboses, the symptomatic VT rate was 2.1% in the PICC group and 10.6% in the CICC group. In the CICC group, 16 of the 47 patients (34%) had the catheter removed for BSI (n = 5), septic thrombophlebitis (n = 4), VT (n = 2), or malfunction (n = 5) a median of 7 days after insertion. In the PICC group, only 6 of the 46 patients (13%) required catheter removal for VT (n = 2) or malfunction (n = 4). At a median follow-up of 30 days, 6 patients in the CICC group died of CR complications versus none of the patients in the PICC group (P = .012). Using PICCs, the reduction in BSI and symptomatic VT decreased mortality from CR infection and venous thromboembolism. In contrast, the CICC approach led to early catheter removal mostly for difficult-to-treat infectious pathogens., Conclusion: Our data have confirmed that BSI and symptomatic VT are the major complications affecting frontline central intravascular device-related morbidity in the leukemia setting. The use of a PICC is safer than that of a CICC and maintains the effectiveness for patients with AML undergoing chemotherapy, with an approximate fourfold lower combined risk of infection or thrombosis at 30 days., (Copyright © 2018 Elsevier Inc. All rights reserved.)