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Mycosis fungoides (MF) is a disease almost impossible to cure. In the context of heavily pretreated patients, the anti-programmed cell death protein 1 (anti-PD-1) pembrolizumab is a valid therapeutic option. The alteration of the PD-1-PD ligand 1 (PD-L1) axis is often present in MF, and this aspect explains the feasibility of this therapy. We report the case of a 60-year-old woman diagnosed with MF in 2003, Olsen stage IA (T1M0NXBO). Since the moment of the diagnosis, she received 10 lines of therapy, with a short duration of response after each one of them. In April 2020, our patient started pembrolizumab 2 mg/kg every 3 weeks, and she achieved a partial response after the 4th cycle, consistent with the modified severity assessment tool (mSWAT) 1, which she is still maintaining after 10 cycles. No grade ≥3 adverse events were recorded. We conclude that pembrolizumab can induce extremely rapid responses in MF, with very low toxicity.

In recent years, novel drugs are available for the patients with relapsed/refractory Hodgkin lymphoma (HL), like immune checkpoint inhibitors (CPi). These drugs have been able to rescue a cohort of patients who subsequently could receive an allogeneic stem-cell transplant (SCT). No data were reported for subsequent autologous SCT (ASCT) after CPi. Here, we report our real-life experience in heavily pretreated HL patients undergoing ASCT as consolidation approach after CPi treatment. A retrospective observational study was conducted. Patients had CPi therapy in the context of clinical trials (n = 6) or in the named patient program (n = 7) between July 2014 and November 2019: 9 out of 13 received pembrolizumab and the remaining four underwent nivolumab. A median of 12 cycles (range, 3-16) of CPi therapy were infused. Thirteen patients underwent ASCT after CPi: 11 (84.6%) patients obtained a complete response (CR) and 2 had progression of disease, with an overall response rate of 84.6%. With a median follow-up of 3.3 years (range, 1.1-5.5), only one CR patient had disease relapse after 3.9 months from ASCT, leading to an estimated disease-free survival of 87.5% at 56.9 months. The estimated 5-year progression-free survival was 73.4% and overall survival was 92.3% at 4.8 years, respectively. No unexpected or cumulative toxicity was observed. Our results indicated that ASCT may represent a further effective therapeutic option as consolidation in HL after CPi treatment that today represents the last conventionally recognized therapeutic line.

First line therapy of patients with marginal zone lymphomas (MZL) is not well established and various regimens with chemo-immunotherapy can be used. Rituximab plus bendamustine (BR) is an effective and manageable treatment option for patients affected by indolent non-Hodgkin lymphoma. The aim of this monocentric retrospective study was to analyze the effectiveness and safety of the use of BR regimen in MZL patients in first line in daily clinical practice. The treatment schedule was rituximab at the dose of 375 mg/m2 on day 1 of each cycle and bendamustine at the dose of 90 mg/m2 on day 2 and 3, every 28 days for a maximum of 6 cycles. We analyzed 65 MZL patients (28 extranodal [EMZL], 23 splenic [SMZL], and 14 nodal [NMZL]) who underwent BR regimen as first line treatment. The median time from diagnosis to therapy was 2.5 months. Final responses were: 38 complete response (CR, 58.5%), 20 partial response and 7 progressive disease, leading to an overall response rate (ORR) of 89.2%. With respect to the histology, the ORR was 89.3% for EMZL, 82.6% for SMZL and 100% for NMZL, respectively (difference not statistically significant). With a median follow-up time of 44.6 months (range, 3.3-175.0 months), 2 (one EMZL after 42 months and one SMZL after 10 months) of 38 (5.2%) CR patients had disease relapse, yielding an estimated disease free survival of 89.2% at 61.1 months. The estimated 6-year progression free survival was 71.8% with 15 relapsed/progressed patients showing lymphoma recurrence within 48 months from end of treatment. The most frequently reported adverse events (any grade) were neutropenia (N = 35, 53.8%), fatigue (N = 15, 23.0%), and nausea (N = 12, 18.4%). All toxicities quickly resolved and no treatment-related death occurred. The BR regimen is effective and feasible in MZL patients inducing prolonged disease control with manageable toxicities.

Purpose One of the most critical issues in the management of Hodgkin lymphoma (HL) patients who resulted as primary relapsed or refractory is to obtain a minimal disease status before autologous stem cell transplantation (ASCT). Finding a salvage regimen able to induce this status without severe toxicity would represent a major achievement in this setting. Methods A single‐center retrospective study was conducted to assess effectiveness and safety of BEGEV (bendamustine, gemcitabine, and vinorelbine) regimen as first salvage setting prior to ASCT in HL patients. Results Forty-three patients were treated in our institution between October 2017 and November 2020. Median age at BEGEV therapy was 35.0 years (range 17.2– 70.0), and the median time from frontline therapy to the first cycle of BEGEV was 79.5 days (range 4–2267). At the end of treatment, 31 patients achieved a complete response (CR), with an overall response rate of 76.7%. Forty-one patients harvested CD34+ cells and 35/43 (81.4%) patients underwent ASCT. With a median follow‐up of 22 months, 4 CR patients had disease relapse, yielding an estimated disease-free survival of 73.9% at 34 months. The estimated 2‐year progression-free survival was 66.7%. Response to first-line chemotherapy did not significantly influence prognosis. Conclusions BEGEV regimen was well tolerated, and reversible haematological toxic effects were the most common adverse events. Real-life data on BEGEV regimen as first salvage setting showed a relevant rate of objective responses and a limited myelotoxicity with no impairment of a subsequent mobilization of peripheral blood stem cells.

BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of themutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long-term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR.

Not available

The follow-up of the pivotal trial and large case series reports of a proportion of patients, between 5% and 9%, with relapsed or refractory Hodgkin lymphoma failing autologous stem cell transplantation and treated with brentuximab vedotin, achieving and maintaining long lasting complete responses with no further treatment. Very long-term data on the outcomes of such patients are indeed underreported. Our institutional experience with patients meeting these characteristics and in continuous complete response for more than 5 years after brentuximab vedotin was reviewed. Five patients achieved a median duration of complete response of 7.4 (range 5.1-8.1) years, and none of them encountered disease relapse or received any subsequent consolidation, including allogeneic transplantation. A proportion of patients failing autologous transplantation and receiving subsequent brentuximab vedotin may reach a long-lasting complete response with no need of further treatment. These patients are therefore considered cured. The role of allogeneic transplantation in such patients is matter of debate.

Purpose: To evaluate the role of F-18-Fluorothymidine (FLT) PET/CT in lymphoma patients with suspected recurrent or residual disease. Methods: Adult lymphoma patients presenting with positive or equivocal F-18-FDG PET/CT at end-treatment or follow-up were prospectively addressed to an additional F-18-FLT-PET/CT. SUV max and tumour-to-background ratios (TBRs) were recorded for the most avid lesion. Biopsy or, when not available, clinical or imaging assessment were employed as standard of reference. Results: Overall 52 patients were recruited. Histology was available in 20/52 patients (38%), proliferation-index (Ki-67) in 14/20. Disease was excluded in 13/52 patients (25%) (one reactive follicular hyperplasia, five reactive-inflammatory tissues, four reactive nodes, two nodal sarcoid-like and one non-specific peri-caecal finding). FDG and FLT scans were concordant in disease restaging in 34/52 patients (65%), whereas in 18/52 cases (35%) relevant discrepancies were recorded. SUV max and TBR were significantly higher in the disease versus the disease-free group, with both tracers (p = 0.0231 and 0.0219 for FDG; p = 0.0008 and 0.0016 for FLT). FLT-SUVmax demonstrated slightly better performance in discriminating benign from malignant lesions (ROC-AUC: 0.8116 and 0.7949 for FLT-SUV max and TBR; 0.7120 and 0.7140 for FDG). Optimal FLT-SUV max cut-offs were searched: three would lead to 95% sensitivity, 81% accuracy, and 39% specificity, whereas seven led to 100%, 41%, and 56% respectively. No statistically significant correlation was observed between the two FLT indices and Ki-67. Conclusions: According to our results in a clinical setting of recurrent or residual lymphoma, FLT is not significantly superior to FDG and it is unlikely that it will be employed independently. FLT may be restricted to a few specific cases, as complementary to standard FDG imaging, to confirm a diagnosis or to define a better target to biopsy. However, due to FLT suboptimal performance, many findings would remain inconclusive, requiring further diagnostic procedures and reducing the effectiveness of performing an additional FLT scan.

Simple Summary CAR T-cell therapies have undoubtedly revolutionized the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma. These therapies represent a valuable new treatment option, yielding impressive complete remission rates and improving survival. The aim of this article is to give an overview of emerging real-world evidence since data from every-day clinical practice are still scarce. We report effectiveness and safety data on 30 patients treated at our Institution. Treatment in this setting with CD19-targeted CAR T-cell therapies for relapsed/refractory B-cell non-Hodgkin lymphoma showed a manageable safety profile and high objective response rate, confirming the encouraging results of the pivotal clinical trials. Abstract Large B-cell lymphomas (LBCL) are the most common types of non-Hodgkin lymphoma. Although outcomes have improved thanks to the introduction of rituximab-based chemoimmunotherapy, certain LBCL still represents a challenge because of initial resistance to therapy or recurrent relapses. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapies approved for patients with relapsed/refractory (R/R) LBCL, based on the results of phase II pivotal single-arm trials ZUMA-1 (for axi-cel) and JULIET (for tisa-cel). Here, we report patients outcomes with axi-cel and tisa-cel in the standard of care (SoC) setting for R/R LBCL, treated at our Institution. Data were collected from patients who underwent leukapheresis between August 2019 and February 2021. Toxicities were graded and managed according to the institution’s guidelines. Responses were assessed as per Lugano 2014 classification. Of the 30 patients who underwent leukapheresis, 18 (60%) received axi-cel, while 12 (40%) tisa-cel. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 10% and 16% patients, respectively. Best objective and complete response rates were 73.3% and 40%, respectively. Treatment in SoC setting with CD19 CAR T-cell therapies for R/R LBCL showed a manageable safety profile and high objective response rate.

The treatment of hairy cell leukemia (HCL) has considerably changed over years. Purine analogues, namely cladribine, now represent the treatment of choice. One hundred and eighty-four patients were followed between 1986 and 2018 and treated according to era-specific guidelines. Responses were classified by combining Consensus Resolution criteria and marrow immunohistochemistry. Patients were grouped according to the number of treatment lines they received. Patients treated first line responded in 86% of cases, with complete response (CR) in 44% of cases. Response rates remained high throughout the first four lines (84%, 81%, 79% for the second line onward, with CR in 38%, 37%, 15% of cases respectively). One hundred and twenty-two patients received cladribine as first line treatment, with a response rate of 86% and a CR rate of 54%. Among the 66 CR patients, 45 (68%) have never received further therapy: 11 patients are in continuous CR between 5 and 10 years after treatment, 14 between 10 and 20 years and three patients at more than 20 years. Median time-to-next treatment (TTNT) for frontline cladribine-treated patients was 8.2 years: partial responders had a significantly shorter median TTNT than CR patients (5.3 years vs median not reached at 25.8 years, p< 0.001). Patients with HCL require subsequent lines of therapy in more than 50% of cases. Purine analogues allow significant response rates when applied first line and upon retreatment. Some patients may enjoy long lasting treatment-free intervals after one course of cladribine.

Primary mediastinal B cell lymphoma is a rare entity and often should be promptly treated as a hematological emergency: The initial treatment decision is crucial for the management of this disease. An observational retrospective study was conducted with the aim to improve information on treatment and outcomes of primary mediastinal B cell lymphoma in real practice. After 12 cycles of MACOP-B regimen (methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone) with or without rituximab, 120 patients out of 151 (79.5%) achieved a complete response and 12 (7.9%) a partial response leading to a global response of 87.4%. The 21-year overall survival is 82.6%; progression-free and disease-free survivals are 69.3% and 86.4%, respectively. Regarding the role of radiotherapy (RT), patients with a negative PET scan after MACOP-B did not undergo RT: One out of these 48 (2.1%) showed a relapse at 11 months. All relapsed/refractory patients who achieved a response with checkpoint inhibitors are still in continuous complete response with a median follow-up of 14 months. Data that we have gathered over a 30-year experience in the treatment of primary mediastinal B cell lymphoma patients clearly indicate that a third-generation chemotherapy regimen such as MACOP-B is feasible and easily deliverable on an outpatient basis. Regarding the unmet medical need of relapsed/refractory patients, new encouraging results occurred with the advent of the checkpoint inhibitors.

Objective: Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous T-cell malignancies representing 5%–10% of aggressive lymphomas. The prognosis is poor for patients with relapsed/refractory (R/R) disease, with a median overall survival of less than 6 months and no standardized treatments. We discuss the role of the phosphatidylinositol 3-kinase (PI3K) γδ inhibitor duvelisib as bridge to allotransplantation in a patient with R/R PTCL. Methods: Case report. Results: A 55-year-old woman diagnosed with relapsed nodal PTCL with T-follicular helper phenotype received PI3K γδ inhibitor duvelisib in the context of the phase II PRIMO clinical trial. After two cycles at a dose of 75 mg twice daily, the patient achieved complete response (CR), which was subsequently consolidated with human leukocyte antigen fully matched unrelated donor allotransplantation. No major toxicities were recorded during the duvelisib treatment period or during hospitalization for allotransplantation. At the latest follow-up, the patient was alive and still in CR 10 months posttransplant. Conclusions: Duvelisib should be further explored as a bridge to allotransplantation in patients with R/R PTCL, given the success and low toxicity in our patient.

Ibrutinib has demonstrated a significant clinical impact in patients with de novo and relapsed/refractory chronic lymphocytic leukemia (CLL), even in cases with unfavorable cytogenetics and molecular markers. All CLL patients’ data treated at our Institute with ibrutinib have been retrospectively reviewed. Forty-six patients received ibrutinib either as frontline (10) or second or more advanced treatment (36). Five patients presented with TP53 mutations; 11 had the deletion of chromosome 17p; 17 displayed an unmutated immunoglobulin variable heavy chain status. The median number of cycles administered was 26. Among patients treated frontline, the best overall response rate (ORR) was 90.0%. In patients receiving ibrutinib as a second or later line ORR was 97.2%. Median progression-free survival was 28.8 and 21.1 months for patients treated frontline and as second/later line, respectively. Median overall survival was not reached for those treated frontline and resulted in 4.9 years for patients treated as second/later line. Grade 3–4 hematological toxicities were neutropenia, thrombocytopenia, and anemia. Grade 3–4 extrahematological toxicities included diarrhea, cutaneous rash, utero-vesical prolapse, vasculitis, and sepsis. Ibrutinib is effective and well tolerated in CLL. Responses obtained in a real-life setting are durable and the safety profile of the drug is favorable.

No abstract available.

Background: Follicular lymphoma (FL) is characterized by frequent relapses and need for multitude lines of therapy, which includes different immunochemotherapy regimens, novel monoclonal antibodies, novel drugs, and autologous or allogenic stem cell transplant. Early use of autologous stem cell transplantation (ASCT) improves prognosis in patients with FL who may be candidates for an aggressive approach. Case presentation: We report the case of a 49-year-old woman with thrombophilia with relapsed/refractory grade 3A FL, heavily pretreated, who achieved third complete remission after high-dose chemotherapy and ASCT, despite experiencing life-threatening adverse events during her treatment history. Conclusions: Stem cell transplantation has emerged as the standard of care for young patients with FL but may be effective also in complex and multirelapsed clinical cases.

Classical Hodgkin lymphoma (cHL) patients who fail autologous stem cell transplantation (ASCT) have extremely poor prognosis with a median overall survival (OS) of two years.[1][1] In this setting, treatment with brentuximab vedotin (BV) resulted in an objective response rate (ORR) of 75%, with 35%

No abstract available.

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Residual masses in patients with mediastinal lymphoma may be positron emission tomography (PET) positive during follow-up also in cases of complete response. The aim of this retrospective study is to verify the reliability of mediastinal PET-positive findings in suggesting disease relapse or progression during follow-up by histological verification. From January 2002 to March 2016, 96 patients with mediastinal lymphoma underwent PET follow-up after front-line treatment. A surgical biopsy was performed to confirm the suspected relapse (for a total of 113 procedures). A lymphoma relapse was diagnosed in 66/102 successful procedures (64.7%). Diagnosis at relapse was concordant with the initial diagnosis in all but 3 cases. Standardized uptake value was significantly higher among patients with relapse than among those who remained in remission (10 versus 5, p

Background Autoimmune manifestations may occur in patients with hairy cell leukemia (HCL), and some rare cases of polyarteritis nodosa and leukocytoclastic vasculitis have been reported. However, data regarding the treatment of these cutaneous manifestations are lacking, given the rarity of the concomitance of HCL and vasculitic syndromes. Case presentation We present a 37-year-old man with paraneoplastic leukocytoclastic vasculitis complicating newly diagnosed HCL. The vasculitis completely resolved after the first 3 weekly administrations of cladribine, which is regarded as the gold-standard treatment for this disease. The underlying leukemia showed refractoriness to the same agent, thus requiring a second line of treatment. Conclusions The clinical picture we have observed is of interest for the following reasons: i) it confirms an existing pathogenetic relationship between this lymphoproliferative disorder and its cutaneous manifestations, as suggested by the prompt resolution of the purpuric lesions upon cladribine administration; ii) it indicates that cladribine is an effective treatment for HCL-related paraneoplastic syndromes, including leukocytoclastic vasculitis; iii) the evolution and the outcomes of the paraneoplastic manifestations may be independent of those of the underlying leukemia, which showed less than a partial response to its initial treatment.

Purpose A large number of new therapeutic agents have been studied for patients with relapsed/refractory follicular lymphoma (FL). Among new therapies, idelalisib, a novel PI3K inhibitor, shows promising results in the management of this disease. Case report We describe the case of a 39-year-old patient with a diagnosis of grade 3a FL and a Follicular Lymphoma International Prognostic Index score of 2, who underwent several lines of therapy (including autologous stem cell transplant) with transient responses or no response at all. The patient was subsequently treated with 5 courses of idelalisib monotherapy, achieving a partial response. No relevant toxicities occurred. The patient underwent allogeneic stem cell transplant (allo-SCT) from an unrelated donor and obtained a complete response, which was confirmed after 3, 6, 9, and 12 months, and is still ongoing. Conclusions As previously reported, the achievement of a good response is predictive for a better outcome after allo-SCT: idelalisib represents an effective treatment option for patients with relapsed/refractory FL, which can also be adopted as a bridge to allo-SCT.

To the editor: Primary mediastinal B cell lymphoma (PMBCL) is a rather infrequent aggressive lymphoma, putatively arising from a transformed thymic B cell. It accounts for

Options are limited for patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) for whom the median overall survival (OS) and progression free survival (PFS) are less than 6 months. Patients who are candidates for allogeneic stem cell transplantation can be cured should they achieve adequate response to salvage therapy prior to transplant. Patients who relapse after transplant or who are not transplant candidates are often treated with sequential single-agent therapies with non-curative intent. Only four agents are FDA-approved for the treatment of R/R PTCL including pralatrexate, romidepsin and belinostat. The objective response rate to each of these agents is only 25-30% and duration of response (DOR) is limited. For a specific subtype of PTCL, namely systemic anaplastic large-cell lymphoma, single-agent brentuximab vedotin (BV) treatment resulted in an 86% overall response rate (ORR) and a 57% complete response (CR) rate in R/R disease. A phase 2 study evaluated the efficacy and safety of BV in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified reporting an ORR of 41% (Horwitz et al, Blood. 2014). We conducted a phase 2 study to determine the antitumor efficacy of single-agent BV (1.8 mg/kg administered intravenously every 3 weeks for a maximum of 16 cycles) as measured by the ORR in R/R CD30+ PTCL patients (PTCL not otherwise specified, AITL and transformed mycosis fungoides). Secondary objectives were to assess duration of tumor control, including duration of response and progression-free survival, overall survival and the safety and tolerability of BV in this setting. ClinicalTrials.gov Identifier: NCT02497131. From September 2015 and September 2019, 25 patients were enrolled and 23 (population for the final analysis) received at least one BV infusion (median 5, range 2-16). There were 10 females, 18 patients were in stage IV and 16 subjects were refractory to the last therapy. Median number of therapies received prior to BV was 2 (range 1-6). Final ORR was 30.4%, with 4 CR. CR patients were 3 PTCL not otherwise specified and 1 AITL with response duration of 2.8, 3.3, 4.5 and 10.7 months, respectively. Best response was achieved at the III cycle. PFS was 4.3% at 12 months (median reached at 4.4 months), OS at 12 months was 49.8% (median reached at 11.4 months) and median DOR was 3.4 months. No correlation between CD30 expression per central review and response was observed. Twenty-one hematological toxicities occurred, 14 of them were grade ≥3 (10 thrombocytopenia and 4 neutropenia, all resolved or improved during BV therapy). Among extra-hematological toxicities (n=26, 3.5% grade ≥3), 7 were serious adverse events. To note, 6 of them (23.1%) were lung infection/pneumonia. Only one peripheral neuropathy (grade 1) occurred. In terms of response, the ORR and PFS in this trial are comparable to those in similar populations studied with both other recently approved agents, such as pralatrexate and romidepsin, and with the other phase 2 study on BV. The ORR of 30% and the OS of in the present study places BV among the active agents for PTCL. Safety concerns emerged about infections, claiming for a strict monitoring for these toxicities. Disclosures Corradini: Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Kite: Consultancy, Honoraria; KiowaKirin: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other; BMS: Other; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for. Zinzani:Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Clinical trial results indicate that romidepsin, a histone deacetylase inhibitor, is a promising treatment in relapsed/refractory T-cell lymphomas (TCLs). This retrospective multicenter study was conducted in patients with relapsed/refractory TCL treated with romidepsin monotherapy through a Named Patient Program (NPP) in Italy. Principal endpoints were overall response rate (ORR), safety, and overall survival (OS). The ORR in 33 evaluable patients was 24.2% with an ORR in the cutaneous TCL of 35.7%. Global OS was 39.3% at 30 months. There were not any specific differences on hematological and extrahematological adverse events. Data from patients treated with romidepsin outside a controlled clinical trial give additional information about the clinical use, efficacy, and toxicity of the drug given to relapsed or refractory TCL patients in a real life context as TCLs are rare diseases and more information is needed. These findings suggest that romidepsin is effective and safe for heavily pretreated TCL patients.

Background: Nivolumab and pembrolizumab are the first two US FDA-approved monoclonal antibodies targeting PD-1 for Hodgkin lymphoma (HL) and provide promising results in the relapsed/refractory setting (HL patients relapsing after autologous stem cell transplantation [ASCT], or with chemorefractory disease and/ or ineligible for ASCT). An interesting area of ongoing research is the possibility of combining different immune checkpoint inhibitors given concomitantly or sequentially in the attempt to maximize the patient responsiveness. Case report: A heavily pre-treated young woman affected by HL, after several attempts, obtained a complete response after ASCT thanks to the bridge with pembrolizumab. After relapse, the patient achieved again a complete response with nivolumab, bridging her to allotransplant. The patient is still in response to a year since the transplant. Discussion and Conclusion: This is the first report which witnesses the safety and the antitumor activity of interchangeable anti-PD1 monoclonal antibodies administered as a retreatment option and as a bridge to allotransplant in a patient who previously got an objective response to another anti-PD1 which brought her to autologous transplant. Retreatment with anti-PD1 monoclonal antibodies could be considered in therapeutic algorithm of relapsed/refractory HL.

Most patients with classical Hodgkin lymphoma (cHL) can be cured with frontline therapy, and those with relapsed or refractory (R/R) disease can often be cured with salvage therapy and autologous stem cell transplantation (ASCT).1-3 However, the prognosis of patients who relapse after or are ineligible to ASCT has historically been extremely poor, with a median overall survival of just over 2 years.1-3 Achieving durable responses in this patient population is a critical treatment goal so far only rarely achieved with conventional chemotherapy.4,5 Brentuximab vedotin (BV) has demonstrated efficacy in patients treated after failure of ASCT, with objective responses seen in 75% of patients in a phase 2 study.6 Recently, because of the unique genetics of cHL, the check point inhibitors nivolumab and pembrolizumab were tested in phase 1 to 2 studies that demonstrated objective responses in 70% to 85% heavily pretreated patients with R/R cHL.7-10 Among the different conventional salvage chemotherapy regimens and conventional single agents, such as bendamustine, BV, nivolumab, and pembrolizumab, there is another drug with interesting results in the setting of R/R cHL, but less known and used: the pegylated liposomal doxorubicin (PLD)

Regarding primary mediastinal large B-cell lymphoma (PMLBCL), there are several controversial topics that warrant further investigation: the superiority of third-generation regimens, the impact of rituximab, the use of involved field radiotherapy (RT) and the assessment of clinical response by positron emission tomography (PET). We report our experience on 74 PMLBCL patients treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and rituximab: an observational retrospective single-centre study was conducted on patients diagnosed and treated between February 2002 and July 2011. All patients were evaluated by computed tomography scan and PET scan; after the final PET evaluation, PET-negative patients were observed, whereas PET-positive patients underwent mediastinal RT. Sixty-one (82.4%) patients achieved a complete response after the MACOP-B plus rituximab regimen; 68.9% presented a positive final PET and were treated with local RT, whereas 31.1% had a negative PET. Five patients relapsed within 12 months. At 10 years, overall survival was 82%, progression-free survival was 87.6% and disease-free survival (DFS) was 90.5% (median follow-up 4 years). No statistically significant differences were observed in DFS between the patients treated also with RT (PET positive) and patients only observed (PET negative): 90.7% vs 90% (p = 0.85), respectively. In our experience, adding rituximab does not change the final results in terms of complete response and DFS utilizing third-generation regimen. Furthermore, the introduction of the PET-guided RT approach leads to a patient-tailored treatment, which preserves the outcome and, at the same time, allows reducing the use of RT. Copyright © 2014 John Wiley & Sons, Ltd.