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The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation., (© 2022 John Wiley & Sons Ltd.)

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18-65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0-56.7), and the 18-month overall survival was 73.1% (95%CI:61.6-81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients., (© 2023. The Author(s).)

Chimeric antigen receptor T (CAR-T) cells are a treatment option for patients with relapse/refractory (R/R) non-Hodgkin lymphoma (NHL), acute lymphoid leukemia and multiple myeloma. To date, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) have been successfully treated with CAR-T cells directed against the CD19 antigen. However, when R/R disease persists after several treatment lines, patients with these diseases are often referred to transplantation centres to receive allogeneic stem cell transplantation (ALLO-SCT). ALLO-SCT and CAR-T cells share mechanism of actions, inducing immune effects of T -cells (and other cells after transplantation) against lymphoma cells, but they differ in several other characteristics. These differences justify unique positioning of each therapy within treatment algorithms. In this paper, we analyzed the results obtained after ALLO-SCT and CAR-T-cell therapy in patients with aggressive lymphomas (large B-cell lymphoma and MCL) to identify the ideal scenarios in which these 2 immunological therapies should be employed., 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 Castagna, Bono, Tringali, Sapienza, Santoro, Indovina, Tarantino, Di Noto, Maggio and Patti.)

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Purpose: A strong prognostic score that enables a stratification of newly diagnosed Hodgkin Lymphoma (HL) to identify patients at high risk of refractory/relapsed disease is still needed. Our aim was to investigate the potential value of a radiomics analysis pipeline from whole-body MRI (WB-MRI) exams for clinical outcome prediction in patients with HL., Materials and Methods: Index lesions from baseline WB-MRIs of 40 patients (22 females; mean age 31.7 ± 11.4 years) with newly diagnosed HL treated by ABVD chemotherapy regimen were manually segmented on T1-weighted, STIR, and DWI images for texture analysis feature extraction. A machine learning approach based on the Extra Trees classifier and incorporating clinical variables, 18 F-FDG-PET/CT-derived metabolic tumor volume, and WB-MRI radiomics features was tested using cross-validation to predict refractory/relapsed disease., Results: Relapsed disease was observed in 10/40 patients (25%), two of whom died due to progression of disease and graft versus host disease, while eight reached the complete remission. In total, 1403 clinical and radiomics features were extracted, of which 11 clinical variables and 171 radiomics parameters from both original and filtered images were selected. The 3 best performing Extra Trees classifier models obtained an equivalent highest mean accuracy of 0.78 and standard deviation of 0.09, with a mean AUC of 0.82 and standard deviation of 0.08., Conclusions: Our preliminary results demonstrate that a combined machine learning and texture analysis model to predict refractory/relapsed HL on WB-MRI exams is feasible and may help in the clinical outcome prediction in HL patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years-mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)-were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice.

Background: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313)., Methods: We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0-9.6; High→Int, HR: 2.3, 95% CI: 1.5-4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential.

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and research_plete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups., (© 2021 by The American Society of Hematology.)

Background: Secondary CNS lymphoma is a rare but potentially lethal event in patients with diffuse large B-cell lymphoma. We aimed to assess the activity and safety of an intensive, CNS-directed chemoimmunotherapy consolidated by autologous haematopoietic stem-cell transplantation (HSCT) in patients with secondary CNS lymphoma., Methods: This international, single-arm, phase 2 trial was done in 24 hospitals in Italy, the UK, the Netherlands, and Switzerland. Adults (aged 18-70 years) with histologically diagnosed diffuse large B-cell lymphoma and CNS involvement at the time of primary diagnosis or at relapse and Eastern Cooperative Oncology Group Performance Status of 3 or less were enrolled and received three courses of MATRix (rituximab 375 mg/m 2 , intravenous infusion, day 0; methotrexate 3·5 g/m 2 , the first 0·5 g/m 2 in 15 min followed by 3 g/m 2 in a 3 h intravenous infusion, day 1; cytarabine 2 g/m 2 every 12 h, in 1 h intravenous infusions, days 2 and 3; thiotepa 30 mg/m 2 , 30 min intravenous infusion, day 4) followed by three courses of RICE (rituximab 375 mg/m 2 , day 1; etoposide 100 mg/m 2 per day in 500-1000 mL over a 60 min intravenous infusion, days 1, 2, and 3; ifosfamide 5 g/m 2 in 1000 mL in a 24 h intravenous infusion with mesna support, day 2; carboplatin area under the curve of 5 in 500 mL in a 1 h intravenous infusion, day 2) and carmustine-thiotepa and autologous HSCT (carmustine 400 mg/m 2 in 500 mL glucose 5% solution in a 1-2 h infusion, day -6; thiotepa 5 mg/kg in saline solution in a 2 h infusion every 12 h, days -5 and -4). The primary endpoint was progression-free survival at 1 year. Overall and complete response rates before autologous HSCT, duration of response, overall survival, and safety were the secondary endpoints. Analyses were in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02329080. The trial ended after accrual completion; the database lock was Dec 31, 2019., Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. 75 patients were assessable. 319 (71%) of the 450 planned courses were delivered. At 1 year from enrolment the primary endpoint was met, 42 patients were progression free (progression-free survival 58%; 95% CI 55-61). 49 patients (65%; 95% CI 54-76) had an objective response after MATRix-RICE, 29 (39%) of whom had a complete response. 37 patients who responded had autologous HSCT. At the end of the programme, 46 patients (61%; 95% CI 51-71) had an objective response, with a median duration of objective response of 26 months (IQR 16-37). At a median follow-up of 29 months (IQR 20-40), 35 patients were progression-free and 33 were alive, with a 2-year overall survival of 46% (95% CI 39-53). Grade 3-4 toxicity was most commonly haematological: neutropenia in 46 (61%) of 75 patients, thrombocytopenia in 45 (60%), and anaemia in 26 (35%). 79 serious adverse events were recorded in 42 (56%) patients; four (5%) of those 79 were lethal due to sepsis caused by Gram-negative bacteria (treatment-related mortality 5%; 95% CI 0·07-9·93)., Interpretation: MATRix-RICE plus autologous HSCT was active in this population of patients with very poor prognosis, and had an acceptable toxicity profile., Funding: Stand Up To Cancer Campaign for Cancer Research UK, the Swiss Cancer Research foundation, and the Swiss Cancer League., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy., Patients and Methods: Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT)., Results: Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky)., Conclusion: cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as follows: 1) treatment-naïve, frail ≥65y, or unfit ≥85y; and 2) relapsed/refractory (R/R) ≥55y. Data were prospectively collected from six Italian centres and compared for efficacy to two reference groups, treated with established iv Rituximab-CHT in 1 st and 2 nd line respectively. Results from April-2011 to March-2018, 17/51(33%) naïve, 21/51(41%) refractory and 13/51(25.5%) relapsed patients started DEVEC; 39/51(76.5%) were de-novo DLBCL; 10/51(19.6%) transformed-DLBCL and 2/51(3.9%) unclassifiable-DLBCL/classical-Hodgkin-lymphoma. The median age was 85y (range=77-93) and 78y (range=57-91) in naïve and R/R respectively and overall the DEVEC patients had very poor features compared to the reference. The rate of grade≥3 haematological-AEs was 43%(95CI=29-58%): G3-neutropenia was the most frequent; grade≥3 extra-haematological-AEs was 13.7% (95%CI=5.4-25.9%), the most frequent was infection. One-year OS and PFS were 67% and 61% for naive, 60% and 50% for reference-naïve respectively; Cox proportional hazard ratio (Cox-PH-ratio) for OS and PFS were 0.69 (95%CI=0.27-1.76;p=.441) and 0.68 (95%CI=0.28-1.62;p=.381) respectively. One-year OS and PFS were 48% and 39% in the R/R, 36% and 17% in the reference-R/R respectively; Cox-PH-ratio for OS and PFS, were 0.76 (95%CI=0.42-1.40; p=.386) and 0.48 (95%CI=0.28-0.82; p=.007) respectively. Conclusion The favourable activity of DEVEC compared to a real-life series and the convenience of an oral administration, may possibly lay the groundwork for a paradigm-shift in the treatment of elderly DLBCL.

Purpose: Ibrutinib has shown activity in non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-germinal center B-cell DLBCL., Patients and Methods: Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety., Results: A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%)., Conclusion: The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.

Objectives: The purpose of our retrospective review of prospectively acquired Whole Body Magnetic Resonance (WB-MRI) scans was to assess the incidence of osteonecrosis in patients who received different chemotherapies., Methods: We evaluated the WB-MRI scans performed on 42 patients with Hodgkin Lymphoma treated by three chemotherapy regimens (6ABVD, 2ABVD + 4BEACOPP, 2ABVD + 8BEACOPP), excluding patients with the main risk factors for osteonecrosis., Results: Six out of seven patients (86 %) who received eight BEACOPP and one out of five patients (20 %) treated by four BEACOPP presented osteonecrosis, with a statistically significant difference of frequency between the two groups of patients (p < 0.05); no injury has been reported in patients treated by only ABVD. Among a total of 48 osteonecrotic lesions observed, 48 % were detected in the knee; multifocal osteonecrosis were detected in six out of seven patients (86 %)., Conclusions: The development of osteonecrosis is strictly related to the chemotherapy protocol adopted and the number of cycles received, with a strong correlation between the dose of corticosteroids included in the BEACOPP scheme and this complication. WB-MRI can be considered as a helpful tool that allows detecting earlier osteonecrotic lesions in patients treated with corticosteroids., Key Points: • Osteonecrosis is a possible complication of patients with Lymphoma treated by chemotherapy. • Osteonecrosis is related to the corticosteroids included within the BEACOPP protocol. • WB-MRI allows detecting osteonecrotic lesions in patients treated with corticosteroids.

Background: The combination of rituximab, bendamustine, and cytarabine (R-BAC) was highly active in a pilot trial of mantle cell lymphoma, but its use was restricted by high haematological toxicity. We aimed to assess the efficacy and safety of an R-BAC regimen with low-dose cytarabine (RBAC500)., Methods: In this multicentre, phase 2 trial, we recruited previously untreated patients with an established histological diagnosis of mantle cell lymphoma from 29 Fondazione Italiana Linfomi centres in Italy. Patients had to be older than 65 years and fit according to the comprehensive geriatric assessment, or aged 60-65 years if they were ineligible for high-dose chemotherapy plus autologous stem-cell transplantation and were fit or unfit. All patients received RBAC500 (rituximab 375 mg/m 2 on day 1, bendamustine 70 mg/m 2 on days 2 and 3, and cytarabine 500 mg/m 2 on days 2-4; all administered intravenously) every 4 weeks for up to six cycles. Primary endpoints were the proportion of patients achieving complete response at the end of treatment and toxicity, defined as the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity. All patients who started at least one cycle of RBAC500 were included in the primary and safety analyses. Using efficacy and toxicity as a composite primary endpoint, we considered the final conclusion positive if more than 28 of 57 patients achieve complete response and fewer than 18 of 57 patients report toxicities. This study is registered with EudraCT, number 2011-005739-23, and ClinicalTrials.gov, number NCT01662050, and is completed., Findings: Between May 2, 2012, and Feb 25, 2014, we enrolled 57 patients (median age 71 years, IQR 67-75). 54 (95%) patients received at least four RBAC500 cycles (three discontinued because of toxicity), and 38 (67%) completed six cycles. Two (4%) had disease progression (one after the fourth cycle and one after the sixth cycle). All 52 (91%, lower limit of one-sided 95% CI 85%) remaining patients achieved complete response at the end of treatment. 23 (40%, upper limit of one-sided 95% CI 53%) of 57 patients had at least one episode of relevant toxicity. The most frequent grade 3-4 haematological toxicities were neutropenia (149 [49%] of 304 cycles) and thrombocytopenia (158 [52%]). Most treatment-related non-haematological adverse events were of grade 1-2, with the most frequent ones being fatigue (14 [25%] patients), nausea or vomiting (12 [21%]), and infusion-related reactions or tumour lysis syndrome (12 [21%]). 41 (72%) patients required a dose reduction. 12 patients died during the study, but no deaths were related to treatment., Interpretation: RBAC500 is an effective treatment for elderly patients with mantle cell lymphoma and, despite not meeting our prespecified safety boundary, haematological toxicity was manageable with appropriate supportive care and dose reduction. Since maintenance therapy is not required, RBAC500 could be considered an option and should be studied in phase 3 trials., Funding: Fondazione Italiana Linfomi and Mundipharma., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Early-interim fluorodeoxyglucose (FDG)-PET scan after two ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy courses (PET-2) represents the most effective predictor of treatment outcome in classical Hodgkin's lymphoma. We aimed to assess the predictive value of PET-2 combined with tissue biomarkers in neoplastic and microenvironmental cells for this disease., Methods: We enrolled 208 patients with classical Hodgkin's lymphoma and treated with ABVD (training set), from Jan 1, 2002, to Dec 31, 2009, and validated the results in a fully matched independent cohort of 102 patients with classical Hodgkin's lymphoma (validation set), enrolled from Jan 1, 2008, to Dec 31, 2012. The inclusion criteria for both the training and validation sets were: the availability of a representative formalin-fixed, paraffin-embedded tissue sample collected at diagnosis; treatment with ABVD with or without radiotherapy; baseline staging and interim restaging after two ABVD courses with FDG-PET; no treatment change based solely on interim PET result; and HIV-negative status. We used Cox multivariate analysis classification and regression tree (CART) to compare the predictive values of these markers with that of PET-2 and to assess the biomarkers' ability to correctly classify patients whose outcome was incorrectly predicted by PET-2., Findings: In multivariate analysis, PET-2 was the only factor able to predict both progression-free survival (hazard ratio [HR] 33·3 [95% CI 13·6-83·3]; p<0·0001) and overall survival (HR 31·3 [95% CI 3·7-58·9]; p=0·002). In the training set, no factor had a stronger adverse predictive value than a positive PET-2 scan and none was able to correctly reclassify PET-2 positive patients. In PET-2 negative patients, expression of CD68 (≥25%) and PD1 (diffuse or rosetting pattern) in microenvironmental cells, and STAT1 negativity in Hodgkin Reed Sternberg cells identified a subset of PET-2 negative patients with a 3 year progression-free survival significantly lower than that of the remaining PET-2 negative population (21 [64%] of 33 [95% CI 45·2-79·0] vs 130 [95%] of 137 [95% CI 89·4-97·7]; p<0·0001). These findings were reproduced in the validation set., Interpretation: The CART algorithm correctly predicted the response to treatment in more than a half of patients who had a relapse or disease progression despite a negative PET-2 scan, thus increasing the negative predictive value of PET-2. In keeping with preliminary results from interim PET response adapted clinical trials of patients with advanced Hodgkin's lymphoma, there might be a non-negligible proportion of treatment failures in the interim PET negative group treated with standard ABVD., Funding: Italian Association for Cancer Research, Bologna Association against leukaemia, lymphoma and myeloma, and Bologna University., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To assess the incidence of collateral findings detected on whole-body magnetic resonance (WB-MRI) scans performed on patients with lymphoma., Materials and Methods: 114 patients (65 male; median age 45.2 years, range 15-86) with histologically confirmed lymphoma (47 Hodgkin, 67 Non-Hodgkin) underwent WB-MRI. The collateral findings were classified into three classes, according to their clinical significance, as follows: not or low significant (class 1), moderately or potentially significant (class 2), and significant (class 3). A Chi-square (χ (2)) test was performed to assess the statistical significance of differences in the incidence of collateral findings based on age (≤50 and >50 years old), gender and histology (Hodgkin and Non-Hodgkin Lymphoma)., Results: Ninety-one of 114 patients (79.8 %) had one or more incidental findings on WB-MRI. Collateral findings were more frequent in class 1 (43 %); abnormalities found in 35 patients (30.7 %) were considered potentially significant, whereas seven patients (6.1 %) demonstrated significant collateral findings requiring immediate treatment or further diagnostic evaluation. Collateral findings were more frequent in subjects over 50 years old compared to those of 50 years old or younger; differences were statistical significant (χ (2) = 8.42, p < 0.05). There were not statistically significant differences related to gender (χ (2) = 0.17, p > 0.05) and histology (χ (2) = 0.24, p > 0.05)., Conclusion: WB-MRI is an attractive procedure that allows to detect incidental abnormalities of organs not involved by disease offering the opportunity to obtain an early diagnosis of asymptomatic life-threatening diseases.

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis can be clinically relevant in patients with diffuse large B-cell lymphoma (DLBCL). We reviewed the outcome of 1,057 DLBCL patients followed from 1984 to 2012 at four centers. LMR was analyzed as a clinical biomarker by receiver-operating characteristic (ROC) analysis and Harrell's C-statistics. Patients were characterized by a median age of 61 years, International Prognostic Index (IPI) score of >2 in 39%, and were treated with a rituximab-containing chemotherapy in 66%. LMR proved strongly predictive for survival in patients treated with rituximab-based programs, but not in those receiving chemotherapy alone. Additionally, an LMR value of ≤2.6 (as determined by ROC analysis) was associated with a worst performance status, a higher lactate dehydrogenase (LDH) level, an advanced clinical stage, and a higher IPI score (P = 0.000). In patients treated with rituximab-supplemented chemotherapy programs, an LMR value of <2.6 was found in most of the primary refractory patients (75%) which proved as the best cutoff to predict both response and survival (P = 0.018). Finally, multivariate analysis and Harrell's C-statistics confirmed the IPI-independent role of LMR on survival (P = 0.0000). In conclusion, LMR is a potent predictor of clinical response and survival in DLBCL treated with rituximab-containing chemotherapy., (Copyright © 2013 Wiley Periodicals, Inc.)

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day -1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follow-up of 16 months (range, 5-42 months), 14 patients were alive, 9 had died from progressive disease, and 1 had died from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effects were grade 4 neutropenia and cytomegalovirus (CMV) reactivation. Major infections were Jacob-Creutzfeldt (J-C) virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis, and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement; and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID no. 141202.