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This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. Trial Registration: ClinicalTrials.gov identifier: NCT02686346 [ABSTRACT FROM AUTHOR]

The study included patients with HL relapsing or refractory after three lines of chemotherapy (including brentuximab-vedotin) and autoHSCT, or four lines of chemotherapy if the patient was not eligible for HSCT. To assess whether some patients might be cured with nivolumab alone as systemic treatment, we analysed the 19 patients who achieved a CR and did not receive a consolidation (concomitant radiotherapy was performed in five patients). Can nivolumab alone cure patients with relapse or refractory Hodgkin lymphoma?. [Extracted from the article]

Classical Hodgkin lymphoma is one of the more frequent lymphomas and is generally considered a highly curable disease with standard first-line chemotherapy and radiotherapy in some cases. Despite these outstanding results, major problems remain unresolved. First, there are still patients who will not be cured with front-line regimens and, second, many patients who are cured of classical Hodgkin lymphoma continue to die prematurely due to the late toxic effects of their therapy. Because the median age of patients with classical Hodgkin lymphoma is in the mid-30s, the disease's impact on the number of years lost from productive life is remarkable. In recent years, the gold standard of chemotherapy (often combined with radiotherapy) has changed, with the approval of immunotherapy mostly in relapse settings. [ABSTRACT FROM AUTHOR]

Purpose: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results: About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P =.0185; IPI score, P =.0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P <.001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. Conclusions: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT. [ABSTRACT FROM AUTHOR]

Patients with classical Hodgkin lymphoma (cHL) typically receive first-line chemotherapy or chemoradiotherapy, and cure rates are high [[1]]. When response was evaluated by prior lines of therapy, ORR was 79.4% (95% CI, 67.3-88.5) among patients who had received at least three prior therapies ( I n i = 63) and 100.0% (95% CI, 63.1-100.0) among patients who had received fewer than three prior therapies ( I n i = 8). However, for patients who have primary refractory cHL that does not respond to salvage chemotherapy or for patients who are ineligible for transplantation because of comorbidity, pembrolizumab could be an effective treatment option. [Extracted from the article]

In KEYNOTE-087, pembrolizumab had a 69% overall response rate and acceptable safety in patients with relapsed/refractory classical Hodgkin lymphoma (rrHL). We assessed health-related quality of life (HRQoL) in KEYNOTE-087. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire 3-level version (EQ-5D) were administered to 206 patients across three cohorts defined by lymphoma progression after: (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV) (n = 69); (2) salvage chemotherapy and BV (n = 79); and (3) ASCT without post-transplantation BV (n = 58). Compliance/completion rates were ≥90% at week 12 and ≥70% at week 24. QLQ-C30 global health status/QoL and EQ-5D visual analog scale scores showed mean increases from baseline in overall health at all assessed timepoints. With few exceptions, mean improvements from baseline to weeks 12 and 24 in QLQ-C30 functional and symptom scores occurred in all cohorts. Clinicaltrials.gov identifier: NCT02453594. [ABSTRACT FROM AUTHOR]

Summary: Tandem stem cell transplantation (SCT) is an option for high‐risk relapsed/refractory Hodgkin Lymphoma (HL) patients. We evaluated the tolerance/efficacy of double autologous or autologous SCT (ASCT) followed by allogenic SCT (alloSCT) in 120 HL patients prospectively registered on a French nationwide database. Median age was 26 (14–56) years. Complete remission rate was 60%, including 33% after a single line, and another 27% after two or more salvage regimens. Partial response rate was 32%, and 8% suffered treatment failure. Overall, 115 (96%) patients underwent a first ASCT, and 73 (61%) had a tandem SCT, including alloSCT in 44 (60%) and ASCT in 29 (40%). The median follow‐up was 43 months (4.8–73.7 months). The two‐year progression‐free survival rate for the whole population and for patients receiving tandem transplant was 56% (95% confidence interval [CI]: 46–65%) and 71% (95% CI: 49–84%), respectively. Among tandem transplants, we observed 20 deaths (17%), 10 of which were transplant‐related (6 alloSCT and 4 ASCT). We suggest that tandem SCT is efficient in high‐risk relapsed/refractory HL patients, although transplant‐related mortality remains high. The benefit of tandem SCT should be balanced with the efficacy of Brentuximab vedotin‐based post‐transplant consolidative strategies in high‐risk relapsed/refractory HL patients. [ABSTRACT FROM AUTHOR]

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The article focuses on the immune checkpoint inhibitor (ICI) named Pembrolizumab for adults with refractory classical Hodgkin lymphoma (HL). It discusses the initial therapies with mechlorethamine, vincristine, procarbazine and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD).

Background: Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era. Methods: We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL. Results: Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIVnegative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients. Conclusions: Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients. [ABSTRACT FROM AUTHOR]

There is no standard of care in elderly classical Hodgkin lymphoma (cHL) patients. ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), the standard chemotherapy for younger patients, is also used in elderly patients but little is known about toxicity and efficacy. We retrospectively analysed 147 patients aged 60 years and over treated with ABVD in three French haematological centres. Treatment regimen modification was applied in 56 patients for toxicity or HL progression. Bleomycin was removed or reduced in 53 patients, mainly for pulmonary toxicity. Neither initial characteristics nor treatment characteristics were found to correlate with lung toxicity. One hundred and seventeen patients achieved a complete remission, 6 a partial remission, 16 had refractory disease and 8 were non-evaluable. Five-year overall survival was estimated at 67%. With a median follow-up of 58 months, 51 patients died and 14% of deaths were related to lung toxicity. Our study confirms the efficacy of ABVD in elderly patients even if results are inferior to those obtained in younger patients with the same regimen. ABVD can be proposed as front-line chemotherapy in selected elderly cHL patients. The frequency of pulmonary events leads us to propose to either reduce the dose of bleomycin or to remove it from the regimen. [ABSTRACT FROM AUTHOR]

Initial spinal cord compression (ISCC) in B-cell non-Hodgkin lymphoma (NHL) is rarely present at diagnosis. We performed a multicenter retrospective analysis of 66 patients with ISCC, including diffuse large B-cell (DLBCL) (70%), follicular (20%), small lymphocytic (6%), marginal zone (2%) and B-cell unclassified (2%) lymphomas, with the aim of describing their management and outcomes, as well as the occurrence of central nervous system (CNS) relapses. All but two patients received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or CHOP-like regimens, with rituximab in 61% of cases. Forty-six patients received CNS prophylaxis. The 5-year overall survival and progression-free survival were 78% and 65% for DLBCL, and 60% and 48% for indolent lymphomas, respectively. CNS relapses occurred in four (6%) patients, all with DLBCL and all in the cerebellum. Initial decompressive procedures, intradural involvement, cerebrospinal fluid infiltration and lack of CNS prophylaxis did not influence survival. Adverse prognostic factors were male sex, poor performance status, elevated lactate dehydrogenase and high age-adjusted international prognostic index. [ABSTRACT FROM AUTHOR]

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare Hodgkin lymphoma distinguished from classical Hodgkin lymphoma (cHL) by the nature of the neoplastic cells which express B-cell markers. We wanted to determine the diagnostic performance of FDG PET/CT in initial assessment and its therapeutic impact on staging. Methods: We retrospectively studied a population of 35 patients with NLPHL (8 previously treated for NLHPL, 27 untreated). All patients underwent an initial staging by pretherapeutic FDG PET/CT. The impact on initial stage or relapse stage was assessed by an independent physician. Results: In a per-patient analysis, the sensitivity of the pretherapeutic FDG PET/CT was 100 %. In a per-site analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of pretherapeutic FDG PET/CT were 100 %, 99 %, 97 %, 100 % and 99 %, respectively. Pretherapeutic FDG PET/CT led to a change in the initial stage/relapse stage in 12 of the 35 patients (34 %). In contrast to previous results established without FDG PET/CT, 20 % of patient had osteomedullary lesions. Conclusion: Pretherapeutic FDG PET/CT has excellent performance for initial staging or relapse staging of NLPHL. [ABSTRACT FROM AUTHOR]

Over 95% of the adult population worldwide is infected with Epstein-Barr virus (EBV). EBV infection is associated with the development of several cancers, including Hodgkin lymphoma (HL). Elevated levels of anti-EBV antibodies have been associated with increased risk of HL. There is growing evidence that genetic factors control the levels of antibodies against EBV antigens. Here, we conducted linkage and association studies to search for genetic factors influencing either anti-viral capsid antigen (VCA) or anti-Epstein Barr nuclear antigen-1 (EBNA-1) IgG levels in a unique cohort of 424 individuals of European origin from 119 French families recruited through a Hodgkin lymphoma (HL) patient. No major locus controlling anti-VCA antibody levels was identified. However, we found that the HLA region influenced anti-EBNA-1 IgG titers. Refined association studies in this region identified a cluster of HLA class II variants associated with anti-EBNA-1 IgG titers (e.g. p = 5×10–5 for rs9268403). The major allele of rs9268403 conferring a predisposition to high anti-EBNA-1 antibody levels was also associated with an increased risk of HL (p = 0.02). In summary, this study shows that HLA class II variants influenced anti-EBNA-1 IgG titers in a European population. It further shows the role of the same variants in the risk of HL. [ABSTRACT FROM AUTHOR]

Background Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Methods Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. Results The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in =25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. Discussion With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Conclusions Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. Trial registration United States registry and results database ClinicalTrials.gov NCT00947856. [ABSTRACT FROM AUTHOR]

Autoimmune hemolytic anemia (AIHA) has been associated with chronic lymphocytic leukemia, non-Hodgkin lymphoma, and classical Hodgkin lymphoma, but to the best of our knowledge, the association of AIHA and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has not been reported previously. A 20-year-old woman presented with conjunctival jaundice, fever, asthenia, and hemoglobin 9.2 g/dL revealing IgG-mediated warmantibody AIHA. Computed tomography (CT) scan and positronemission tomography (PET) scan showed mediastinal and axillary lymph nodes with increased [18F]-fluorodeoxyglucose uptake. A mediastinal lymph node was biopsied during mediastinoscopy, and NLPHL was diagnosed by an expert hematopathologist. The hemoglobin level declined to 4.6 g/dL. The treatment consisted of four 28-day cycles of R-ABVD (rituximab 375mg/m² IV, adriamycin 25mg/m² IV, bleomycin 10mg/m² IV, vinblastine 6mg/m² IV, and dacarbazine 375mg/m² IV, each on days 1 and 15). Prednisone was progressively tapered over 10 weeks. After the first chemotherapy cycle, the hemoglobin level rose to 12 g/dL. After the four cycles, PET and CT scans showed complete remission (CR). At the last followup (4 years), AIHA and NLPHL were in sustained CR. [ABSTRACT FROM AUTHOR]

The risk of developing Hodgkin lymphoma ( HL) is increased in immunodeficiencies or during the treatment of some autoimmune diseases. The development of new therapeutic agents has highlighted the risk of unusual lymphoid proliferations, particularly classical HL (c HL). We report the clinicopathological findings of 13 c HL arising in patients treated for a primary haematological malignancy. Eight patients had received an immunomodulator, protein tyrosine-kinase inhibitor or monoclonal antibody, which may have contributed to the c HL development. Most patients had disseminated disease with poor prognostic factors at cHL diagnosis. Despite the initial presentation, good outcomes were achieved with standard c HL chemotherapy. [ABSTRACT FROM AUTHOR]

Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin-bleomycin-vinblastine-dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide-etoposide-oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m days 1-3), etoposide (150 mg/m days 1-3) and oxaliplatin (130 mg/m day 1). Patients <65 years old received high-dose therapy followed by autologous stem-cell transplantation (HDT-ASCT). Response was assessed by computed and positron-emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose-reductions. Twenty-six patients underwent HDT-ASCT. With median follow-up at 5 years, the 5-year overall and event-free survival rates were 74% and 63%, respectively. IVOx is a well-tolerated outpatient regimen for relapsed HL, that does not hamper stem-cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens. [ABSTRACT FROM AUTHOR]

Accurate staging of Hodgkin’s lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. 18F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant 18F-FDG PET/CT. Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and 18F-FDG PET/CT. Results of BMB were not available at the time of 18F-FDG PET/CT imaging. Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on 18F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on 18F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy 18F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient. 18F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging. [ABSTRACT FROM AUTHOR]

The article focuses on a research about the long-term results of the registered patients and their rate of histologic transformation (HT) rate to diffuse large B-cell lymphoma (DLBCL). It states that 164 patients with nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) served as subjects of the study. Findings show that there was no significant difference in the overall survival rate after HT of patients who underwent autologous stem cell transplantation (ASCT) and the others.

SGN-30, a chimeric anti-CD30 monoclonal antibody, has demonstrated potent preclinical antitumour activity in both Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). We conducted an open-label, Phase II study to determine the safety and objective response rate of SGN-30 in 79 patients with refractory/recurrent HL ( n = 38) or systemic ALCL ( n = 41). Each course of SGN-30 comprised 6 weekly intravenous infusions, followed by a 2-week treatment-free period. Patients had received a median of 3 (range 1–5) prior regimens of chemotherapy or systemic therapy. The initial 40 patients received 6 mg/kg weekly; the latter 39 patients received 12 mg/kg weekly. In the ALCL group, two patients achieved a complete response and five additional patients achieved a partial response, with response durations ranging from 27 to 1460+ d. No objective responses were observed in the HL group; however, 11 patients (29%) had stable disease (duration 62–242 days). Although adverse events were common, most were mild or moderate, and no specific pattern of adverse events was observed in either disease group. These results demonstrate that weekly administration of SGN-30 is safe, with modest clinical activity in patients with ALCL. [ABSTRACT FROM AUTHOR]

Despite a high curability rate, some patients with Hodgkin lymphoma (HL) fail to respond to, or relapse after, primary conventional treatment. This review aims to identify prognostic factors at relapse and guidelines for treatment in relapsed HL. Patients with relapsed HL should be identified according to their prognostic factors at relapse (duration of remission and extranodal disease or stage). This enables relapsing patients to be separated in to three different prognostic groups; primary refractory patients should be included in the unfavourable group because of their poor prognosis. All relapsed HL should receive second-line chemotherapy and the response to this chemotherapy is crucial for the outcome. Benefit of autologous stem-cell transplantation (ASCT) has been shown in a large randomized study and, although is often proposed in relapsed HL, it may be not necessary in the rare group of patients with stage I/II and late relapse who can receive additional radiotherapy after response to chemotherapy. Patients with intermediate and unfavourable relapse should receive high-dose chemotherapy and ASCT when chemosensitive; the first goal is to achieve this chemosensitivity. For patients in the unfavourable group, including refractory patients, the role of tandem HDT or allogeneic SCT will be discussed and should be proposed for patients not in complete remission at the time of HDT. [ABSTRACT FROM AUTHOR]

Background: In patients with lymphoma who had a poor prognosis, pretransplantation 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) was important for the evaluation of response and outcome. However, little is known about the correlation of FDG-PET with post-transplantation PET. The current study was designed to ascertain whether positive pretransplantation PET images are modified by the conditioning regimen. Methods: Sixty consecutive patients who had achieved remission and underwent consolidation by autologous stem cell transplantation (ASCT) had PET images obtained before ASCT (after 3 or 4 chemotherapy cycles) and 100 days after ASCT. The correlation was explored between the presence of abnormal 18-FDG uptake (PET positive) or its absence (PET negative) and patient outcomes. Results: Before ASCT, 31 patients achieved complete remission (CR), and 23 patients achieved uncertain CR. Before ASCT, 44 patients (75%) were had negative PET images; and, after ASCT, 48 patients (80%) had negative PET images. One year after ASCT, the estimated event-free survival (EFS) rate was 80% in patients who had negative pre-ASCT PET images compared with 43% in patients who had positive pre-ASCT PET images (P = .0002). The EFS rate was 81% in patients who had negative post-ASCT PET images compared with 25% in patients who had negative post-ASCT PET images (P < .0001). In multivariate analysis, only the results for pre- and post-ASCT PET images retained prognostic value, with relative risks of failure estimated at 4.9 and 11.9, respectively. Conclusions: A positive pre-ASCT PET image indicated a high risk of ASCT failure, which was increased by a positive post-ASCT PET image. For patients with lymphoma who have positive pre-ASCT PET images, more investigations using new treatment approaches will be required. For patients who have negative pre-ASCT PET images, obtaining post-ASCT PET images does not seem to be mandatory. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytoid lymphomas (LPL) are non-Hodgkin's lymphomas characterized by a proliferation of lymphoplasmacytoid cells or plasma cells with intracytoplasmic monoclonal Ig. The LPL are low-grade B-cell neoplasms close to B chronic lymphocytic leukemia with plasmacytoid differentiation. They show an indolent course, typically affect older men, and present as a disseminated disease with predominantly nodal involvement. Nevertheless, localized forms, some of them extranodal, have been described. The cases that best represent the range of radiographic findings on X-ray, CT, and MR imaging are presented. [ABSTRACT FROM AUTHOR]

The article offers information on the treatment of Hodgkin lymphoma with anti PD-1 monoclonal antibodies. Topics discussed include information on the unconventional immune-related phenomena regarding tumor response or progression; discussions on the immune-related pattern of response in solid tumors, along with abscopal effect and hyperprogression; and the information on the medical imaging detects of adverse events (irAE) in solid tumors.

The article discusses a study on pegylated liposomal doxorubicin (PLD) treatment for Hodgkin lymphoma (HL) patients relapsing after stem cell transplation and high dose therapy. It informs that the study included mediastinal radiation therapy, supra-diaphragmatic radiotherapy, and standard chemotherapy regimens. The study found that patients can be treated for long periods with low-toxicity monotherapy such as vinblastine, brentuximab vedotin, and panobinostat.

The article offers information about the implementation of targeted therapies to treat classical Hodgkin lymphoma. It provides details on the positive results using targeted therapy for salvage chemotherapy before conducting autotransplantation as well as discusses the application of high dose therapy and other treatment for refractory patients and the use of brentuximab vedotin.

Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (<1%) in the PET-driven treatment group (one from septic shock and one from acute myeloblastic leukaemia).Interpretation: PET after two cycles of induction BEACOPPescalated chemotherapy safely guided treatment in patients with advanced Hodgkin lymphoma and allowed the use of ABVD in early responders without impairing disease control and reduced toxicities. PET staging allowed accurate monitoring of treatment in this trial and could be considered as a strategy for the routine management of patients with advanced Hodgkin lymphoma.Funding: Programme Hospitalier de Recherche Clinique. [ABSTRACT FROM AUTHOR]

Purpose For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors ( NCT00005584 ). Patients and methods Patients aged 15–70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4–5 nodal areas, mediastinum/thoracic ratio ≥ 0.35, erythrocyte sedimentation rate (ESR) ≥ 50 without B-symptoms or ESR ≥ 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPP baseline -IFRT (n = 255). Results Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPP baseline -IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90%CI, -0.7%–8.8%) and of 1.1% (90%CI,-3.5%–5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP) baseline more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD). Conclusions The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP baseline were more toxic than four or six cycles of ABVD. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is still frequent. The programmed cell death protein 1 (PD-1) pathwayblocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT. However, PD-1 blocking strategy can increase the risk of graft-versus-host disease (GVHD) inmurine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in 6 patients (30%) after nivolumab initiation. All 6 patients had prior history of acute GVHD. The patients with nivolumab-induced GVHD were managed by standard treatment for acute GVHD. Two patients diedasa resultofGVHD, 1ofprogressive disease and1of complicationsrelatedto a secondallo-HCT.Overall response ratewas 95%.At amedianfollow-upof370days, the 1-yearprogression-freesurvival ratewas 58.2%(95%CI, 33.1%-76.7%) andtheoverallsurvival rate was 78.7% (95% CI, 52.4%-91.5%). Among 13 patients still in response, 6 received a single dose of nivolumab and 7 remain on nivolumab. Compared with standard options for this indication, our results show that nivolumab is effective with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) occuring during pregnancy is a rare condition, and management relies on sparse literature. The specificity of pregnancy requires the clinician to take into account the clinical emergency, the stage of the lymphoma, the trimester of pregnancy, and the patient's choices. The main objective is twofold: to limit the risk of toxicity and adverse events for both mother and fetus, without reducing the chances of a successful outcome. Current literature data suggest that the use of ABVD-type polychemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is associated with obstetrical events and long-term fetal toxicity. We report here the results of a homogeneous management considering wait-and-see, vinblastine monotherapy and ABVD polychemotherapy options. The outcomes in terms of obstetrical complications, response rate, and overall survival (100 %) reinforce the idea that strategies that do not involve the use of multidrug therapy are possible and are associated with very good results. • Literature about management of Hodgkin Lymphoma during pregnancy is controversial. • Polychemotherapy may expose to obstetrical issues and long term fetal toxicity. • Wait and see attitude and vinblastine monotherapy should be considered. • Strategy without routine polychemotherapy results in excellent outcomes. [ABSTRACT FROM AUTHOR]

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS (P < .0001) and OS (P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm3) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm³). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cytokines are important immune mediators in classical Hodgkin lymphoma. [•] SNPs in cytokine genes could influence cytokine production. [•] IL10, TNFA, IL6, IL1RN, INFG, CCL17 SNPs were not associated with cytokine levels. [•] Overall, none of these SNPs influence progression-free survival of CHL patients. [•] In analysis by EBV status, TNFA−308G>A influenced prognosis of EBV negative CHL. [Copyright &y& Elsevier]