German Hodgkin Study Group

Köln, Germany

German Hodgkin Study Group

Köln, Germany
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Borchmann P.,University of Cologne | Haverkamp H.,University of Cologne | Lohri A.,Cantonal Hospital Baselland | Lohri A.,Swiss Group for Clinical Cancer Research SAKK | And 23 more authors.
The Lancet Oncology | Year: 2017

Background: Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPPescalated) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. Methods: In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPPescalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPPescalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPPescalated (BEACOPPescalated group) or BEACOPPescalated plus rituximab (R-BEACOPPescalated group). PET-2 was assessed using a 5-point scale with 18FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPPescalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m2 (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPPescalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component, stratified according to centre, age, stage, international prognostic score, and sex. The primary efficacy endpoint was 5 year progression-free survival, analysed in the intention-to-treat population. We are reporting this second planned interim analysis as the final report of the trial. The trial is registered with ClinicalTrials.gov, number NCT00515554. Findings: Between May 14, 2008, and May 31, 2011, we enrolled 1100 patients. 440 patients had a positive PET-2 and were randomly assigned to either the BEACOPPescalated group (n=220) or the R-BEACOPPescalated group (n=220). With a median follow-up of 33 months (IQR 25-42) for progression-free survival, estimated 3 year progression-free survival was 91·4% (95% CI 87·0-95·7) for patients in the BEACOPPescalated group and 93·0% (89·4-96·6) for those in the R-BEACOPPescalated group (difference 1·6%, 95% CI -4·0 to 7·3; log rank p=0·99). Common grade 3-4 adverse events were leucopenia (207 [95%] of 218 patients in the BEACOPPescalated group vs 211 [96%] of 220 patients in the R-BEACOPPescalated group), and severe infections (51 [23%] vs 43 [20%] patients). Based on a futility analysis, the independent data monitoring committee recommended publication of this second planned interim analysis as the final result. Six (3%) of 219 patients in the BEACOPPescalated group and ten (5%) of 220 in the R-BEACOPPescalated group died; fatal treatment-related toxic effects occurred in one (<1%) patient in the BEACOPPescalated group and three (1%) in the R-BEACOPPescalated group, all of them due to infection. Interpretation: The addition of rituximab to BEACOPPescalated did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin's lymphoma. However, progression-free survival for PET-2 positive patients was much better than expected, exceeding even the outcome of PET-2-unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high-risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin's lymphoma. Funding: Deutsche Krebshilfe; Swiss State Secretariat for Education, Research and Innovation (SERI); and Roche Pharma. © 2017 Elsevier Ltd.


Sasse S.,University of Cologne | Sasse S.,German Hodgkin Study Group | Klimm B.,University of Cologne | Klimm B.,German Hodgkin Study Group | And 14 more authors.
Annals of Oncology | Year: 2012

Background: To evaluate long-term toxicity and efficacy of a combined modality strategy including extended-field radiotherapy (EF-RT) or involved-field radiotherapy (IF-RT), the German Hodgkin Study Group carried out a follow-up analysis in patients with early unfavorable Hodgkin's lymphoma (HL). Patients and methods: One thousand two hundred and four patients were randomized to four cycles of chemotherapy followed by either 30 Gy EF- or 30 Gy IF-RT (HD8 trial); 532 patients in each treatment arm were eligible. Results: At 10 years, no arm differences were revealed with respect to freedom from treatment failure (FFTF) (79.8% versus 79.7%), progression-free survival (79.8% versus 80.0%), and overall survival (86.4% versus 87.3%). Non-inferiority of IF-RT was demonstrated for the primary end point FFTF (95% confidence interval for hazard ratio 0.72-1.25). Elderly patients had a poorer outcome when treated with EF-RT. So far, 15.0% of patients in arm A and 12.2% in arm B died, mostly due to secondary malignancies (5.3% versus 3.4%) or HL (3.2% versus 3.4%). After EF-RT, there were more secondary malignancies overall (58 versus 45), especially acute myeloid leukemias (11 versus 4). Conclusion: Radiotherapy intensity reduction to IF-RT does not result in poorer long-term outcome but is associated with less acute toxicity and might be associated with less secondary malignancies. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.


Boll B.,University of Cologne | Boll B.,German Hodgkin Study Group | Bredenfeld H.,German Hodgkin Study Group | Gorgen H.,German Hodgkin Study Group | And 21 more authors.
Blood | Year: 2011

Approximately 20% of all Hodgkin lymphoma (HL) patients are older than 60 years and have a poor prognosis, mainly because of increased treatment-related toxicity resulting in reduced overall dose intensity and more treatment-related 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.clinicaltrials.gov as #NCT00147875. © 2011 by The American Society of Hematology.


Boll B.,University of Cologne | Boll B.,German Hodgkin Study Group | Goergen H.,German Hodgkin Study Group | Arndt N.,Stiftungsklinikum Mittelrhein | And 21 more authors.
Journal of Clinical Oncology | Year: 2013

Purpose Progression or relapse of Hodgkin lymphoma (HL) is common among older patients. However, prognosis and effects of second-line treatment are thus far unknown. Patients and Methods We investigated second-line treatment and survival in older patients with progressive or relapsed HL. Patients treated within German Hodgkin Study Group first-line studies between 1993 and 2007 were screened for refractory disease or relapse (RR-HL). Patients with RR-HL age < 60 years at first-line treatment were included in this analysis. Results We identified 105 patients (median age, 66 years); 28%, 31%, and 41% had progressive disease, early relapse, or late relapse, respectively. Second-line treatment strategies included intensified salvage regimens (22%), conventional polychemotherapy and/or salvage-radiotherapy with curative intent (42%), and palliative approaches (31%). Median overall survival (OS) for the entire cohort was 12 months; OS at 3 years was 31% (95% CI, 22% to 40%). A prognostic score with risk factors (RFs) of early relapse, clinical stage III/IV, and anemia identified patients with favorable and unfavorable prognosis (≤ one RF: 3-year OS, 59%; 95% CI, 44% to 74%; ≤ two RFs: 3-year OS, 9%; 95% CI, 1% to 18%). In low-risk patients, the impact of therapy on survival was significant in favor of the conventional polychemotherapy/salvage radiotherapy approach. In high-risk patients, OS was low overall and did not differ significantly among treatment strategies. Conclusion OS in older patients with RR-HL can be predicted using a simple prognostic score. Poor outcome in high-risk patients cannot be overcome by any of the applied treatment strategies. Our results might help to guide treatment decisions and evaluate new compounds in these patients. © 2013 by American Society of Clinical Oncolog.y.


Boll B.,University of Cologne | Boll B.,German Hodgkin Study Group | Gorgen H.,German Hodgkin Study Group | Fuchs M.,University of Cologne | And 20 more authors.
Journal of Clinical Oncology | Year: 2013

Purpose Older patients with Hodgkin lymphoma (HL) account for approximately 20% of all HL patients. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy is regarded as standard of care in these patients. However, little is known on feasibility and efficacy of ABVD in this age group. Patients and Methods We analyzed the feasibility and efficacy of four cycles of ABVD in older patients age 60 to 75 years with early-stage HL who were treated within the German Hodgkin Study Group (GHSG) HD10 and HD11 trials; results were compared with those of younger patients treated within these trials. Results In total, 1,299 patients received four cycles of ABVD, and 117 of those patients were older than age 60 years (median, 65 years). In 14% of older patients, treatment was not administered according to protocol, mainly because of excessive toxicity. The mean delay of treatment was twice as high in the older patients (2.2 v 1.2 weeks). Fifty-nine percent of older patients achieved a relative dose-intensity of at least 80% compared with 85% of younger patients. Major toxicity (WHO grade 3 and 4), including leucopenia, nausea, infection, and others, was documented in 68% of older patients with a treatment-related mortality of 5%. Complete response was achieved in 89% of older patients, 3% had progressive disease, and 11% relapsed. At a median observation time of 92 months, 28% of the patients had died, and the 5-year progression-free survival estimate was 75% (95% CI, 66% to 82%). Conclusion In patients age ≥ 60 years with HL, four cycles of ABVD is associated with substantial dose reduction, treatment delay, toxicity, and treatment-related mortality. © 2013 by American Society of Clinical Oncology.


Klimm B.,German Hodgkin Study Group | Franklin J.,University of Cologne | Stein H.,Berlin Reference Center for Lymphoma and Hematopathology | Eichenauer D.A.,German Hodgkin Study Group | And 5 more authors.
Journal of Clinical Oncology | Year: 2011

Purpose: To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-depleted classical Hodgkin's lymphoma (LDCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL). Patients and Methods: From a total of 12,155 evaluable patients with biopsy-proven HL treated within the German Hodgkin Study Group trials HD4 to HD15, 10,019 patients underwent central expert pathology review. Eighty-four patients with LDCHL (< 1%) were identified and confirmed. The median follow-up time was 67 months. Results: Patients with LDCHL, compared with patients with other histologic subtypes, presented more often with advanced disease (74% v 42%, respectively; P < .001) and "B" symptoms (76% v 41%, respectively; P < .001). Other risk factors were also more frequent in patients with LDCHL. Complete remission or unconfirmed complete remission was achieved in 82% of patients with LDCHL compared with 93% of patients with other HL subtypes (P < .001), and more patients with LDCHL had progressive disease. At 5 years, progression-free survival (PFS) and overall survival (OS) were significantly lower in patients with LDCHL compared with patients with other HL subtypes (PFS, 71% v 85%, respectively; P < .001; OS, 83% v 92%, respectively; P = .0018). However, when analyzing the subgroup of patients who underwent treatment with intensified or dose-dense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, patients with LDCHL (n = 39) had similar outcomes when compared with patients with other subtypes of HL (n = 3,564; P = .61). Conclusion: LDCHL has a different pattern from other HL subtypes with more clinical risk factors at initial diagnosis and significantly poorer prognosis. Patients with LDCHL should be treated with modern dose-intense treatment strategies. © 2011 by American Society of Clinical Oncology.


Halbsguth T.,German Hodgkin Study Group | Halbsguth T.,Universitatsklinikum Cologne | Borchmann P.,German Hodgkin Study Group | Borchmann P.,Universitatsklinikum Cologne
Onkologe | Year: 2010

Elderly patients with Hodgkin's lymphoma still have a relative poor prognosis especially in advanced stages. Due to the lack of large randomized studies, no evidence-based standard treatment can be defined. In routine practice patients with early stages disease are treated with a combined modality strategy of 2-4 cycles A(B)VD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by involved-field radiation therapy. Patients with advanced stage disease are usually treated with 6-8 cycles of A(B)VD followed by radiotherapy to residual disease. A more aggressive regimen would be preferable but is frequently not feasible in this patient cohort due to comorbidities. Therefore, the aim of future studies is still to develop regimens with high anti-tumor efficacy but low toxicity. These studies require an elderly-specific design that takes comorbidities, innovative treatment approaches and quality of life issues during therapy and follow-up into account. Therefore, the GHSG (German Hodgkin Lymphoma Study Group) has initiated a phase I/II study to investigate the new immunomodulatory drug lenalidomide in combination with AVD in elderly patients with early unfavorable or advanced stage disease. © Springer-Verlag 2010.


Boll B.,German Hodgkin Study Group | Boll B.,Universitatsklinikum Cologne | Borchmann P.,German Hodgkin Study Group | Borchmann P.,Universitatsklinikum Cologne | And 2 more authors.
Onkologe | Year: 2010

Experimental therapy strategies are currently restricted to patients with Hodgkin's lymphoma who relapse after high dose chemotherapy. Monoclonal antibodies, radio-immunoconjugates, immunotoxins, cellular therapeutics and small molecules, such as immunomodulatory substances, deacetylase inhibitors and m-TOR inhibitors have shown clinically relevant effectiveness. Currently ongoing clinical trials will yield an insight into the biology and provide novel, more effective and less toxic therapeutics for patients in all stages of Hodgkin's lymphoma. © Springer-Verlag 2009.

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