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Background and purpose A real‐time biomarker in chemotherapy‐induced peripheral neurotoxicity (CIPN) would be useful for clinical decision‐making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN. Methods This single‐center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score–clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6–12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2. Results Eighty‐two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR‐CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001). Conclusions A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma. VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment. Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0–74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0–73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8–13·8). 52 (44%; 95% CI 35–53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3−4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported. These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile. Daiichi Sankyo.

Fludarabine-cyclophosphamide-rituximab (FCR) has been the gold standard front-line treatment for fit CLL patients until novel agent’s introduction. Decision between either time-limited FCR or “endless” Bruton’s tyrosine kinase inhibitor (BTKi) therapy may be difficult in fit IGHV-mutated-non-TP53 cases. We describe the outcomes after front-line FCR in 110 CLL patients from 5 centres in Catalonia, Spain, over a period of more than 10 years. ORR was 96.3% and CR 74.5%. Median second-treatment free survival (TFS1) was 6.2 years and median OS was 10.8 years. 50 (45.5%) patients required a subsequent therapy. Median third-treatment free survival was better for BTKi than for chemotherapy ± antiCD20 strategies (not reached vs 3.1 years, p  = 0.003). Only 50 (45.5%) patients completed 6 cycles of FCR, and the main reason for discontinuation was cytopenia 29 (26.4%). 15 (13.6%) patients developed a second cancer, and 5 (4.5%) patients experienced a Richter's transformation (RT). At the end of follow-up, 50 (45.5%) patients remained in CR. Response rates, TFS1, OS, RT, and second cancers did not differ between patients treated with 6 vs 4 cycles of FCR. In conclusion, front-line FCR treatment leads to very long CR in almost half of patients, and BTKi yields excellent outcomes in relapsed patients.

Trial registration: ClinicalTrials.gov number: NCT01777152

Extramedullary multiple myeloma (EMM) has an overall survival of 6 months and occurs in 20% of multiple myeloma (MM) patients. Genetic and epigenetic mechanisms involved in EMM and the therapeutic role of new agents for MM are not well established. Besides, well-characterized preclinical models for EMM are not available. Herein, a patient-derived orthotopic xenograft (PDOX) was generated from a patient with an aggressive EMM to study in-depth genetic and epigenetic events, and drug responses related to extramedullary disease. A fresh punch of an extramedullary cutaneous lesion was orthotopically implanted in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ(NSG) mouse. The PDOX mimicked histologic and phenotypic features of the tumor of the patient. Cytogenetic studies revealed a hyperploid genome with multiple genetic poor-prognosis alterations. Copy number alterations (CNAs) were detected in all chromosomes. The IGH translocation t(14;16)(q32;q23)IGH/MAF was already observed at the medullary stage and a new one, t(10;14)(p?11-12;q32), was observed only with extramedullary disease and could be eventually related to EMM progression in this case. Exome sequencing showed 24 high impact single nucleotide variants and 180 indels. From the genes involved, only TP53 was previously described as a driver in MM. A rather balanced proportion of hyper/hypomethylated sites different to previously reported widespread hypomethylation in MM was also observed. Treatment with lenalidomide, dexamethasone and carfilzomib showed a tumor weight reduction of 90% versus non-treated tumors, whereas treatment with the anti-CD38 antibody daratumumab showed a reduction of 46%. The generation of PDOX from a small EMM biopsy allowed us to investigate in depth the molecular events associated with extramedullary disease in combination with drug testing.

Objectives: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. Methods: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. Results: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. Conclusions: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population.

Total metabolic tumor volume (TMTV) is a promising quantitative biomarker for therapy assessment and prognosis in Hodgkin Lymphoma affected patients that allows prediction of patient outcome. The aim of this study was to evaluate the TMTV reproducibility between different sources of variability in tumor delimitation such as SUV-based thresholds (2.5, 41% and 50%) and software tools (Beth Israel plugin (BI) and LIFEx). Effect of contouring procedure both including single and multiple regions of interest was also studied in patients with multiple lesions, and optimal cut-offs for each studied method were displayed to compare the effect on prognosis. Strong alikeness in TMTV was found for 2.5 under software choice . Best accuracy in contouring compared to visual assessment of the disease was found for BI multiple ROI and LIFEx single ROI drawing. Similar cut-offs were found between both software for all considered thresholds, but best resemblance and highest cut-off due to an overestimation of the TMTV was found for 2.5 SUV. Our findings suggest that optimal reproducibility in TMTV is found for SUV > 2.5 threshold under choice of contouring methodology or software tool, meaning that overestimation of the TMTV threshold using 2.5 looks to be preferable than underestimation with 41% and 50%.

The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action.

Background Clinical outcomes of novel coronavirus 2019 disease (COVID‐19) in onco‐hematological patients are unknown. When compared to non‐immunocompromised patients, onco‐hematological patients seem to have higher mortality rates. Aims We describe the characteristics and outcomes of a consecutive cohort of 24 onco‐hematological patients with COVID‐19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. Methods and Results Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID‐19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22‐82) years. Median follow‐up in survivors was 14 (9‐28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1‐10) and 10 (3‐18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D‐dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID‐19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID‐19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (−55%) and chemotherapy sessions (−19%). A significant increase in phone visits was reported (+581%). Conclusion COVID‐19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting.

Objectives Chimeric antigen receptor T cells (CARTs) against CD19 antigen represent an effective therapy for relapsed/refractory diffuse large B‐cell lymphoma (rrDLBCL). There is no diagnostic test able to predict which patients with residual disease will relapse from those that will reach a delayed complete response. Positron emission tomography/computed tomography scan (PET‐CT) is characterized by a significant number of false positive results after immunotherapy. Circulating tumor DNA (ctDNA) may be a good‐useful tool to quantify minimal residual disease and for monitoring disease response. Methods We present a patient with DLBCL treated with CART cells in which we tested the combined use of ctDNA and PET‐CT scan. Results Disease reassessment with PET‐CT scan showed a partial remission (3 weeks) and a very good partial remission (2 months). A clinical progression at 3 months was confirmed with PET‐CT scan. Levels of ctDNA progressively decreased and became undetectable. An initial increase in KMT2D p.E4385G variant allele frequency confirmed disease progression. Conclusions Our case shows how the complementary use of ctDNA and PET‐CT scan could be a helpful tool in the clinical management of these patients.