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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]

Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches. This review aims to give a comprehensive overview of novel agents in Hodgkin lymphoma that have been recently or are currently being evaluated in clinical trials. In addition to dedicated sections on brentuximab vedotin (BV) and immune checkpoint inhibitors, other emerging substances and concepts are discussed. In doing so, this review compares trial results regarding safety and efficacy. A special focus lies on the effect novel agents will have on the different treatment settings faced by clinicians involved in the treatment of Hodgkin lymphoma. [ABSTRACT FROM PUBLISHER]

The article discusses a study on the use of the oral deacetylase inhibitor panobinostat to treat patients with Hodgkin lymphoma. The study examined 27 patients who received panobinostat and 14 patients who were given placebos. The results revealed relapse in patients after they received high dose chemotherapy and underwent autologous stem cell transplants.

Background Hodgkin lymphoma (HL) is one of the most common malignancies in young adults and one of the most curable cancers worldwide. With interim PET-scan, HL treatment is in the process of being modified: a negative or positive interim PET separates good and poor responders to initial therapy; therefore, deescalated or escalated additional treatment is currently being evaluated in clinical trials. Methods The Cochrane Library, MEDLINE and conference proceedings were searched until 05.2015 for randomized controlled trials (RCTs) comparing FDG-PET-adapted therapy to standard treatment in untreated early stage HL patients with a negative PET-scan. Two review authors independently screened search results and extracted relevant study data. Hazard ratios (HR) were used for time-to-event data and risk rations (RR) for dichotomous data, with 95% confidence intervals (CI). If trials were considered sufficiently clinically homogenous, fixed-effect model was used to pool data. Results Three RCTs involving a total of 1480 participants were included in the meta-analysis. Only one trial provided data for OS, without evidence for a difference between both arms (HR 0.51; 95% CI 0.15–1.68). All three trials assessed progression free survival, which was inferior in the PET-adapted arms (without radiotherapy) compared to the standard treatment arms (HR 2.40; 95% CI 1.63–3.53). Adverse events were reported in one study only, without evidence for a difference between both arms. There were no data on long-term adverse events, quality of life and treatment-related mortality available Conclusion To date, no robust data on survival and adverse events are available. However, this systematic review found that PFS was significantly decreased in the PET-adapted treatment arm (without radiotherapy) in early stage HL patients. [ABSTRACT FROM AUTHOR]

Treatment for Hodgkin lymphoma is effective for about 85% of the patients. A gold-standard for the 15% of relapsing patients is still missing. High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) has shown efficacy and safety for patients, but up to date no survival benefit revealed. After systematic literature search we identified three randomised controlled trials from 1663 total hits. Meta-analysis of two trials (157 patients) showed a statistically significant increase in progression-free survival (hazard ratio 0.55, 95% confidence interval 0.35–0.86) for patients treated with HDCT and ASCT compared to conventional chemotherapy, but no difference in overall survival nor increased adverse events. The third trial (241 patients) showed an statistically significant increase in infections and 5% more treatment-related mortalities following sequential HDCT plus HDCT and ASCT compared to HDCT plus ASCT, without differences in the efficacy endpoints overall survival or progression-free survival. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the outcome and risk factors of patients with Hodgkin lymphoma (HL) who relapse or progress after autologous stem cell transplant (ASCT). Researchers evaluated 149 patients. They found that 75% died within 65 months after recurrence of HL following ASCT and that nearly 40% died within one year.

Although several promising approaches for the treatment of relapsed/refractory diffuse large B‐cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long‐term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost‐ and time‐sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof‐of‐principle for its ability to predict outcomes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which the authors comment on a phase II prospective clinical trial concerning the use of cetuximab, an anti-epidermal growth factor receptor antibody, in treating refractory or relapsed multiple myeloma both on its own and combined with dexamethasone.

Introduction: Chimeric antigen receptor positive T cell (CAR-T cell) treatment became standard therapy for relapsed or refractory hematologic malignancies, such as non-Hodgkin's lymphoma and multiple myeloma. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between centers in the prevention, diagnosis, and management of short- and long-term complications. Methods: To capture the current CAR-T cell management among German centers to determine the medical need and specific areas for future clinical research, the DAG-HSZT (Deutsche Arbeitsgemeinschaft für Hämatopoetische Stammzelltransplantation und Zelluläre Therapie; German Working Group for Hematopoietic Stem Cell Transplantation and Cellular Therapy) performed a survey among 26 German CAR-T cell centers. Results: We received answers from 17 centers (65%). The survey documents the relevance of evidence in the CAR-T cell field with a homogeneity of practice in areas with existing clinical evidence. In contrast, in areas with no – or low quality – clinical evidence, we identified significant variety in management in between the centers: management of cytokine release syndrome, immune effector cell-related neurotoxicity syndrome, IgG substitution, autologous stem cell backups, anti-infective prophylaxis, and vaccinations. Conclusion: The results indicate the urgent need for better harmonization of supportive care in CAR-T cell therapies including clinical research to improve clinical outcome. [ABSTRACT FROM AUTHOR]

Objectives: The treatment of relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) changed remarkably since the European Medicines Agency‐approved chimeric antigen receptor T‐cell (CAR‐T) therapies (axicabtagene ciloleucel [axi‐cel], lisocabtagene maraleucel [liso‐cel], tisagenlecleucel [tisa‐cel]) for the third‐line onwards (3+L), and targeted therapies (polatuzumab vedotin–bendamustine–rituximab [pola‐BR], tafasitamab–lenalidomide [Tafa‐L]) for the second‐line (2L) onwards. As associated rising treatment costs represent an economic burden, the cost‐effectiveness of transplant‐ineligible R/R DLBCL interventions was assessed from a German healthcare payer's perspective, using the efficiency frontier (EF) approach. Methods: A systematic literature review was performed to determine the clinical benefit concerning median overall survival (OS) of bendamustine–rituximab (BR), rituximab–gemcitabine–oxaliplatin (R‐GemOx), axi‐cel, liso‐cel, tisa‐cel, pola‐BR, and Tafa‐L. First‐year treatment costs (drug and medical services costs) were calculated. Results were merged on two‐dimensional graphs illustrating 2L and 3+L EFs. Results: Second‐line EF is formed by BR (median OS 11.49 months, €23 958) and Tafa‐L (45.7, €104 541), 3+L EF is formed by R‐GemOx (12.0, €29 080), Tafa‐L (15.5, €104 541), and axi‐cel (18.69, €308 516). These interventions build the respective cost‐effectiveness thresholds for novel interventions. Conclusions: Using the EF approach, the currently most cost‐effective interventions (based on cost‐effectiveness ratios) in the indication of R/R DLBCL were identified to guide international reimbursement decisions. [ABSTRACT FROM AUTHOR]

Summary: B‐cell content in the tumour microenvironment (TME) of classic Hodgkin lymphoma (HL) is known to be associated with prognosis. Here we demonstrate that whole slide image analysis using routinely available slides predicts outcomes in patients treated with ABVD in a prospective trial with a high B‐cell content being associated with a favourable prognosis. B cells in the TME did not correlate with B cells in peripheral blood. In the TME maturation, stages of B cells (naive and memory) were consistent. However, we detected down‐regulation of CD73 in HL with low B cells suggestive of an antibody‐independent function of B cells in the TME of HL. [ABSTRACT FROM AUTHOR]

Objectives: Patients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). Methods: Patients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989). Results: Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. Conclusion: Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1. [ABSTRACT FROM AUTHOR]

Introduction: Patients with hematologic disease are at high risk of morbidity and mortality from COVID‐19 due to disease‐inherent and therapy‐related immunodeficiency. Whether infection with the SARS‐CoV2 omicron variant leads to attenuated disease severity in these patients is currently unknown. Methods: We assessed clinical and laboratory parameters in 61 patients with underlying hematologic conditions with a SARS‐CoV2 omicron variant infection confirmed by nucleic acid amplification testing. Results: Fifty patients reported symptoms of COVID‐19, most commonly fatigue (37 patients, 60.66%) and cough (32 patients, 52.46%). 39.34% of patients reported fever. Dyspnea was reported by 10 patients and 7 patients (11.48%) required oxygen therapy. Anosmia and ageusia were relatively rare, occurring in less than 10% of patients. Severity of SARS‐CoV2 infection could be assessed in 60 patients. Five cases of critical illness leading to ICU admission occurred during the observation period. Overall mortality was 9.84% in this patient cohort, with heterogeneous causes of death. The majority of omicron‐infected hematologic patients experienced mild symptoms or remained asymptomatic. Discussion: In this study, symptoms of COVID‐19 tended to be milder than described for previous SARS‐CoV2 variants. However, the extent to which attenuated severity of omicron‐variant SARS‐CoV2 infection is caused by altered viral pathogenicity or pre‐existing host immunity cannot be inferred from our data and should be investigated in larger prospective studies. [ABSTRACT FROM AUTHOR]

Background: Burkitt lymphoma (BL) and diffuse large B‐cell lymphoma (DLBCL) are aggressive B‐cell non‐Hodgkin lymphomas (B‐NHL) with a generally favorable prognosis after immunochemotherapy. The outcome of BL is superior to DLBCL. In 2016, a distinct group of lymphomas displaying characteristics of both BL and DLBCL (high grade B‐cell lymphoma, HGBL) was introduced into the WHO classification. Histopathological discrimination of BL, DLBCL, and HGBL may be challenging. Data on the frequency of histopathological difficulties resulting in revision of the final diagnosis of BL/DLBCL/HGBL and its impact on the prognosis are limited. Methods: We assessed histopathological features and clinical outcomes of 66 patients with suspected diagnosis of BL at the reporting institution between 2010 and 2020. Results: The median age was 51 years (range 19‐82) and final histopathological diagnosis revealed BL (n = 40), DLBCL (n = 12), or HGBL (n = 14). Patients with DLBCL and HGBL were either treated with DLBCL‐directed (83.3% and 35.7%) or BL‐directed (16.7% and 64.3%) protocols. Patients in whom diagnosis was revised from DLBCL to BL after initiation of DLBCL‐directed treatment had a significantly inferior progression‐free survival (PFS) than patients initially diagnosed with BL (p = 0.045), thus resembling rather the prognosis of DLBCL/HGBL. There was no difference between patients with DLBCL and HGBL, respectively, regarding PFS and OS (p = 0.38 and p = 0.27). Conclusion: These results suggest that timely and precise histopathological diagnosis as well as reference histopathological review of the underlying lymphoma is critical to determine up‐front treatment strategies. Consequently, selection of more aggressive treatment protocols in case of difficulties with discrimination between DLBCL/HGBL/BL may be a reasonable approach. [ABSTRACT FROM AUTHOR]

Summary: Reinduction chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second‐line standard of care for transplant‐eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high‐dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant‐eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase‐I‐part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end‐point of computed tomography (CT)‐based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT‐based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end‐point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy. [ABSTRACT FROM AUTHOR]

Summary: We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET‐2) tended to be more common (P = 0·1078). Five‐year progression‐free survival [hazard ratio (HR) = 0·86; 95% confidence interval (CI) = 0·49–1·47] and overall survival (HR = 0·85; 95% CI = 0·49–1·51) did not differ between the groups after study treatment with PET‐2‐guided escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Thus, advanced NLPHL is often associated with atypical growth patterns but their prognostic impact is compensated by PET‐2‐guided escalated BEACOPP. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to determine the effectiveness of brentuximab vedotin (BV) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) in the clinical practice setting using most recent results. A total of 32 observational studies reporting on treatment patterns, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events were found. After four cycles, a random-effect model yielded pooled ORR and CR rates of 62.6% (95% confidence interval (CI): 56.0–68.9; I2 = 9.7%) and 32.9% (95% CI, 20.8–46.3, I2 = 64.8%), respectively. Regarding survival, 1-year, 2-year, and 5-year PFS ranged from 52.1% to 63.2%, 45.2% to 56.2%, and 31.9% to 33.0%, respectively. OS rates were 68.2–82.7%, 58.0–81.9%, and 58.0–62.0%, respectively. Most common adverse events were hematological toxicities (neutropenia: 13.3–23%, anemia: 8.8–39.0%, and thrombocytopenia: 4–4.6%), and grade ≥3 peripheral neuropathy (3.3–7.3%). This study supports the effectiveness and safety of BV in R/R cHL patients in the real-world setting. [ABSTRACT FROM AUTHOR]

Summary: The activity of natural killer (NK) cells is regulated by surface receptors, which direct target cell recognition. NKp30 (Natural Cytotoxicity Receptor 3) induces target cell lysis and is also crucial for the interaction with dendritic cells. So far, the cellular ligands for NKp30 have remained elusive. Here we show that the nuclear factor HLA-B-associated transcript 3 (BAT3) was released from tumor cells, bound directly to NKp30, and engaged NKp30 on NK cells. BAT3 triggered NKp30-mediated cytotoxicity and was necessary for tumor rejection in a multiple myeloma model. These data identify BAT3 as a cellular ligand for NKp30. We propose a concept for target cell recognition by NK cells beyond “missing self” and “induced self,” mediated through a tumor cell-derived extracellular factor. [Copyright &y& Elsevier]

A letter to the editor is presented regarding activity of cetuximab as single agent in a patient with relapsed multiple myeloma.

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]

What is it that we actually see when looking at PET (positron emission tomography)-positive signals in Hodgkin lymphoma (HL)? Thus, the question of how to manage PET-positive lesions at the end of frontline therapy in HL is indeed crucial, because undertreating a disease that can be cured with firstline treatment in 80-90% of cases must definitely be avoided. As a result the authors concluded that it may not always be decisive to perform a biopsy for PET-positive residual mediastinal tissue after frontline therapy and that it was safe and appropriate to first closely observe asymptomatic patients instead of directly intensifying treatment. In the GHSG HD15 trial Engert et al. assessed whether administering RT only to patients with persistent PET-positive residues after chemotherapy was justifiable compared to earlier trials where irradiation was given to all initial bulky findings and all residual disease. [Extracted from the article]

The optimal treatment of patients with relapsed or refractory nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. To shed more light on treatment options and outcome, we performed an analysis using the database of the German Hodgkin Study Group (GHSG). Ninety-nine patients who had received first-line treatment within 12 prospective GHSG studies conducted between 1993 and 2009, and subsequently developed disease recurrence (n = 91) or had primary disease progression (n = 8), were included. At initial NLPHL diagnosis, the median age was 40 years and 76% of patients were male. First-line treatment consisted of radiotherapy (RT) alone (20%), chemotherapy with or without RT (74%), and the anti-CD20 antibody (Ab) rituximab (6%), respectively. The median follow-up from initial diagnosis was 11.2 years. The median time to disease recurrence was 3.7 years. The applied salvage approaches included single-agent anti-CD20 Ab treatment or RT alone (37%), conventional chemotherapy (CT) with or without anti-CD20 Ab treatment with or without RT (27%) and high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) (31%). No salvage treatment was given in 4% of patients. The 5-year progression-free survival and overall survival estimates after NLPHL recurrence were 75.6% and 89.5% (74.1% and 97.2% after single-agent anti-CD20 Ab treatment or RT alone; 68.0% and 77.8% after CT with or without anti-CD20 Ab treatment with or without RT; 84.6% and 89.8% after HDCT and ASCT). Hence, patients with relapsed or refractory NLPHL had a good overall prognosis. Factors such as time to disease recurrence and previous treatment may guide the choice of the optimal salvage approach for the individual patient. [ABSTRACT FROM AUTHOR]

We examined real-world data on management of relapsed/refractory Hodgkin lymphoma (R/R HL) in five European countries and the consistency of these data with guideline recommendations. Retrospective clinical and epidemiologic data for 509 patients with R/R HL treated between January 2014 and March 2015 were collected at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was 46.3 years; 73.3% were receiving second-line therapy for a first relapse during the reporting period. Most patients received ABVD as front-line chemotherapy, except in Germany where escalated BEACOPP was used more often. The proportion of patients receiving stem cell transplantation (SCT) was 44%; 85% of transplants occurred at first relapse. Brentuximab vedotin (BV) was usually administered after autologous SCT, and was initiated for 65% of patients following SCT failure. Our findings suggest that R/R HL management across these countries is broadly consistent with guideline recommendations and that BV is well-integrated into treatment pathways. [ABSTRACT FROM AUTHOR]

[Display omitted] • Radiotherapy in the context of CAR T-cell therapy may support the local disease control without increased toxicity. The neurotoxicity of CAR T-cells is less pronounced after bridging RT. • After further disease progression and treatment with salvage radiotherapy, localized relapses had better outcomes and better local therapy responses, compared to advanced stage relapses. • Salvage therapy including radiotherapy may, in case of localized relapses, have a positive impact on patients' OS, compared to salvage therapy without radiotherapy. Chimeric antigen receptor (CAR) T-cell therapy has improved the limited overall survival (OS) of patients with intensively pretreated diffuse large B-cell lymphoma (DLBCL). However, the potentially life-threatening toxicities of CAR T-cells and early relapses remain a challenge. As suggested by smaller monocentric analyses, radiotherapy (RT) in combination with CAR T-cells may have an immunomodulatory effect. In this multicentric retrospective analysis, we investigated potentially synergistic effects of RT and CAR T-cells. Of 78 patients from four centers who received CAR T-cell therapy for DLBCL, 37 patients underwent bridging RT or received salvage RT. RTs (median 36 gray) were well tolerated. Therapy response and disease control of CAR T-cell therapy were comparable after bridging RT or bridging systemic therapy. High-grade neurotoxicity tended to occur less frequently after bridging RT. After further disease progression, patients with localized relapses showed better outcomes, compared to those in advanced stage. In the subgroup with localized relapse, patients receiving salvage RT had an increased OS, vs. those without salvage RT (1-year OS rate 89% vs. 38%, p = 0.03). Our analysis demonstrated that RT in combination with CAR T-cells led neither to high-grade toxicities, nor to a decreased response rate. We observed better outcomes of salvage therapies in patients with localized relapses vs. those with advanced stage relapses. Especially the patients who received salvage RTs for localized relapses seem to benefit more. Further analyses are necessary to clarify whether specific synergistic effects exist, such as an enhanced anti-tumor effect of CAR T-cells from RT sensitizing. [ABSTRACT FROM AUTHOR]

The article provides information on a study which observed the link between different blood count parameters at baseline with response and progression-free survival (PFS) in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL) patients treated with the anti-PD1 antibody, nivolumab. Topics discussed include role of eosinophils as co-effectors of the immune response, and results of the study.

Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Therefore, using bleomycin has been questioned in older Hodgkin lymphoma (HL) patients, especially in early-stage HL. We therefore analyzed feasibility, toxicity, and efficacy of ABVD or AVD in 287 older early-stage favorable HL patients. We included patients ≥60 years of age in the German Hodgkin Study Group HD10 and HD13 trials randomized to either 2 cycles of ABVD (2 x ABVD; n = 137) or AVD (23AVD; n= 82), each followed by involved-field radiotherapy (IF-RT), with patients randomized to 43ABVD1IFRT (n568). Patients' median age was 65 years (range, 60-75) with comparable patient and disease characteristics. Grade III-IV adverse event rates were similar in patients receiving 23AVD and 2 x ABVD (40% and 39%, respectively), but considerably higher in patients receiving 43ABVD (65%). Similarly, BLT was rare in patients receiving 2 x ABVD/AVD, but occurred in 7/69 (10%) of patients randomized to 43ABVD, with 3 lethal events. In conclusion, no effects of bleomycin on toxicity rates were detectable in older patients receiving 2 cycles of chemotherapy. However, we found a high risk of severe toxicity of bleomycin in older HL patients receiving more than 2 cycles of ABVD. These trials are registered at www.clinicaltrials.gov and www.isrctn.com as #NCT00265018 (HD10) and #ISRCTN63474366 (HD13). [ABSTRACT FROM AUTHOR]

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease ( n = 9), comorbidity ( n = 4) and unknown reasons ( n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT ( n = 4) or allogeneic SCT ( n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL. [ABSTRACT FROM AUTHOR]

Approximately 20% of all Hodgkin lymphoma (HL) patients are older than 60 years and have a poor prognosis, mainly because of increased treatmentrelated toxicity resulting in reduced overall dose intensity and more treatmentrelated mortality. To possibly improve the treatment of elderly HL patients, the German Hodgkin Study Group developed a new regimen, PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine). In this multicenter phase 2 study, elderly HL patients in early unfavorable and advanced stages received 6 to 8 cycles of PVAG and additional radiotherapy if they were not in complete remission (CR) after chemotherapy. Endpoints included feasibility, acute toxicity, and response rate. Fifty-nine patients 60 to 75 years of age (median, 68 years) were eligible for analysis; 93% had advanced stage disease. WHO grade 3/4 toxicities were documented in 43 patients; 46 patients responded with CR/CR uncertain (78%). Within 37 months median observation time, 15 progressions or relapses and 17 deaths were observed, of which 8 were related to HL and 1 was the result of treatment-related toxicity. The 3-year estimates for overall survival and progression-free survival were 66% (95% CI, 50%78%) and 58% (95% CI, 43%-71 %), respectively. We conclude that PVAG is safe and feasible in elderly HL patients. This trial was registered at www.clinlcaltrials.gov as #NCT00147875. [ABSTRACT FROM AUTHOR]

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for 5% of Hodgkin lymphoma cases. The disease is characterized by a strong CD20 expression on the malignant cells and a more indolent clinical course compared with classic HL. Anti-CD20 antibody treatment has shown clinical activity In relapsed NLPHL. In this phase 2 trial, we Investigated rituximab In newly diagnosed stage IA NLPHL patients. Four weekly applications at 375 mg/m2 were given. Among the 28 evaluabie patients, overall response rate was 100%, 24 patients (85.7%) achieved complete remission, and 4 (14.3%) achieved partial remission. At a median follow-up of 43 months, overall survival was 100%; progression-free survival at 12. 24, and 36 months was 96.4%, 85.3%, and 81.4%, respectIvely. No grade 3 or 4 toxicity was observed, Although treatment results with rituximab appear interior compared with radiotherapy and combined-modality approaches in early-stage patIents, investigation of anti-CD20 antibody-based combinations in NLPHL Is warranted. This study was registered at www.clinicaitrials.gov as #NCT00346684. [ABSTRACT FROM AUTHOR]

Focuses on the shedding-influencing role of structural elements of the ectodomain of CD30, a known substrate of tumor necrosis factorα-converting enzyme. Antibody-dependent inhibition of CD30 shedding; Regulation of the releasing enzyme in a feedback fashion by the soluble product through competitive inhibition; Modulation of sCD30 release by the cleavage product.