Rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: long-term follow-up of a phase 2 study from the German Hodgkin Study Group

Leukemia ◽  
2019 ◽  
Vol 34 (3) ◽  
pp. 953-956 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Annette Plütschow ◽  
Michael Fuchs ◽  
Sylvia Hartmann ◽  
Martin-Leo Hansmann ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Study Group ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
German Hodgkin Study Group ◽  
Phase 2 Study ◽  
Long Term Follow Up ◽  
Stage Ia

scholarly journals Treatment of Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): An Analysis from the German Hodgkin Study Group (GHSG)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3058-3058 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Annette Pluetschow ◽  
Michael Fuchs ◽  
Karolin Behringer ◽  
Boris Böll ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Combined Modality Treatment ◽  
Study Group ◽  
Excellent Outcome ◽  
German Hodgkin Study Group ◽  
Long Term Follow Up ◽  
Stage Ia

Abstract Introduction: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for about 5% of all HL cases. As compared with classical HL (cHL), NLPHL is characterized by the absence of CD30 and the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. Given a more indolent clinical course, especially early-stage NLPHL is often treated less aggressive than classical HL (cHL). In stage IA patients, radiotherapy (RT) alone is applied at most institutions. However, this clinical practice is not based on data from prospective clinical trials with sufficient follow-up. To shed more light on the optimal treatment of stage IA NLPHL, we performed an analysis including patients with long-term follow-up treated within German Hodgkin Study Group (GHSG) clinical trials. Patients: A total of 256 stage IA NLPHL patients treated within 7 prospective GHSG studies between 1988 and 2009 were included in the analysis. Treatment consisted of combined-modality treatment (CMT) (n=72), extended-field RT (EF-RT) (n=49), involved-field RT (IF-RT) (n=108) or four weekly doses of the anti-CD20 antibody rituximab (n=27). Results: The median age at NLPHL diagnosis was 38.5 years (range: 17-75); 194/256 (75.8%) patients were male and 62/256 (24.2%) patients were female. Median follow-up for the whole patient group was 91 months (98 months for CMT, 118 months for EF-RT, 87 months for IF-RT, 49 months for rituximab). All patients responded to treatment irrespective of the treatment modality applied. At 8 years, progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 94.5% for CMT, 84.3% and 95.7% for EF-RT and 91.9% and 99.0% for IF-RT; 4-year PFS and OS rates for patients treated with rituximab were 81.0% and 100%. Seventeen patients developed a second malignancy in the course of follow-up (8 after CMT, 3 after EF-RT, 4 after IF-RT, 2 after rituxmab). Nine of these second malignancies were solid tumors (4 after CMT, 2 after EF-RT, 1 after IF-RT, 2 after rituximab) and 8 were hematologic malignancies (4 after CMT, 1 after EF-RT, 3 after IF-RT, none after rituximab). A total 12 deaths occurred. The most common cause of death was cardiac failure (n=3). Only one patient died from NLPHL. Conclusion: Based on this large analysis with long-term follow-up, IF-RT should be the standard of care for stage IA NLPHL. Treatment with single agent rituximab is associated with an increased event rate when compared with IF-RT and should therefore not be routinely used in stage IA NLPHL patients. However, given the shorter follow-up in comparison with CMT, EF-RT and IF-RT, final conclusions regarding rituximab especially in terms of treatment-related late sequelae cannot yet be drawn. Addition of chemotherapy does not improve the excellent outcome achieved with RT alone. Disclosures Off Label Use: Rituximab in NLPHL.

Long-Term Follow-Up of BEACOPPescalated Chemotherapy in Patients with Advanced-Stage Hodgkin Lymphoma on Behalf of the German Hodgkin Study Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 211-211
Author(s):  
Engert Andreas ◽  
Jeremy Franklin ◽  
Volker Diehl
Keyword(s):  
Hodgkin Lymphoma ◽  
Secondary Malignancy ◽  
Tumor Control ◽  
Study Group ◽  
Advanced Stage ◽  
Secondary Aml ◽  
German Hodgkin Study Group ◽  
Long Term Follow Up

Abstract The HD9 trial of the German Hodgkin Study Group (GHSG) compared two different doses (baseline and escalated) of the novel chemotherapy regimen BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage Hodgkin lymphoma (HL). The previous analysis with a median follow-up of 5 years showed improved tumor control (FFTF) and overall survival (OS) for BEACOPPescalated. Since BEACOPPescalated had been associated with more toxicity as compared with ABVD we report the results of long-term follow-up of 1196 patients enrolled and randomized in that study. The median follow-up was 112 months; a total of 370 centres contributed. Patients received one of three chemotherapy regimens: 8 cycles of COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) alternating with ABVD (doxorubicin, bleomycin, vinblastin, and dacarbazine), 8 cycles of standard-dose BEACOPP or 8 cycles of escalated-dose BEACOPP. At 10 years, FFTF rates were 64%, 70% and 82%, OS rates were 75%, 80%, and 86 for COPP-ABVD (arm A), BEACOPPbaseline (arm B), and BEACOPPescalated, respectively (p < 0,001). Importantly, BEACOPPescalated was also significantly better than BEACOPPbaseline in terms of FFTF (p < 0.0001) and OS (p = 0.0053). Death due to HL occurred in 11.5%, 8.1% and 2.8% in arms A, B, and C, respectively. 74 second malignancies were documented, including secondary acute myeloid leukaemias (1,7,14), Non-Hodgkin lymphoma (7,8,5), and solid tumors (7,16,9) in arms A, B, and C respectively. The corresponding overall secondary malignancy rates were 6.7%, 8.9% and 6.8%. Importantly, the risk of secondary AML (sAML), although increased in this study after BEACOPPescalated, amounts to 0.9% in our follow-up study with BEACOPPescalated (HD12) in 1502 advanced-stage HL patients randomized and four years median follow-up. Although the higher rate of secondary AML after BEACOPPescalated in HD9 most likely occurred by chance, interestingly, 70% of patients in this group had additional radiotherapy whereas only 39% were radiated in HD12. Taken together, the 10 years follow-up of BEACOPPescalated chemotherapy demonstrates a stabilized significant improvement in long-term FFTF and OS for advanced-stage HL. Although for formal prove the results of ongoing prospective randomized comparisons with 8 cycles of ABVD might be required, these results clearly challenge ABVD as standard of care for this patient population.

Long-Term Course of Patients With Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the German Hodgkin Study Group

2015 ◽  
Vol 33 (26) ◽  
pp. 2857-2862 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Annette Plütschow ◽  
Michael Fuchs ◽  
Bastian von Tresckow ◽  
Boris Böll ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Survival Rates ◽  
Combined Modality Treatment ◽  
Study Group ◽  
German Hodgkin Study Group ◽  
Stage Ia ◽  
Overall Survival Rates

Purpose The optimal treatment of stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined. Thus, we performed an analysis using the database of the German Hodgkin Study Group. Patients and Methods The long-term outcome of 256 patients with stage IA NLPHL was evaluated. Patients had received combined-modality treatment (CMT; n = 72), extended-field radiotherapy (EF-RT; n = 49), involved-field radiotherapy (IF-RT; n = 108), or four weekly standard doses of rituximab (n = 27) within German Hodgkin Study Group clinical trial protocols between 1988 and 2009. Results The median age at NLPHL diagnosis was 39 years (range, 16 to 75 years). Most patients were male (76%). The whole patient group had a median follow-up of 91 months (CMT: 95 months; EF-RT: 110 months; IF-RT: 87 months; rituximab: 49 months). At 8 years, progression-free survival and overall survival rates were 88.5% and 98.6% for CMT, 84.3% and 95.7% for EF-RT, and 91.9% and 99.0% for IF-RT, respectively. Patients treated with rituximab had 4-year progression-free and overall survival rates of 81.0% and 100%, respectively. A second malignancy during the course of follow-up was diagnosed in 17 (6.6%) of 256 patients. A total of 12 deaths occurred. However, only one patient died from NLPHL. Conclusion Tumor control in this analysis was equivalent with CMT, EF-RT, and IF-RT. Therefore, IF-RT, which is associated with the lowest risk for the development of toxic effects, should be considered as standard of care for patients with stage IA NLPHL. Rituximab alone is associated with an increased risk of relapse in this patient population.

Beacoppescalated Followed By Radiotherapy of Initial Bulk or Residual Disease in Advanced Stage Hodgkin Lymphoma: Long-Term Follow up of the HD9 and HD12 Trials of the German Hodgkin Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 923-923 ◽  
Author(s):  
Stefanie Kreissl ◽  
Bastian von Tresckow ◽  
Helen Goergen ◽  
Heinz Haverkamp ◽  
Stephanie Sasse ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Residual Disease ◽  
Study Group ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Second Malignancies ◽  
Long Term Follow Up

Abstract Background: The HD9 trial established 8 cycles of BEACOPPescalated followed by radiotherapy (RT) of initial bulk or residual tumors as German Hodgkin Study Group (GHSG) standard of care for advanced stage Hodgkin Lymphoma (HL) at that time. The succeeding HD12 trial aimed at reducing treatment intensity while maintaining efficacy. It compared 8 cycles of BEACOPPescalated with 4 cycles of BEACOPPescalated followed by 4 cycles of BEACOPPbaseline ("4+4" regimen) as well as RT with no RT of initial bulk or residual disease. Although tumor control is outstanding, long-term safety of BEACOPPescalated still is a matter of concern, and the need of consolidating RT in advanced stage HL is discussed controversially. We therefore performed a long-term follow up of the HD9 and HD12 trials in order to address these open questions. Patients and Methods: Between February 1993 and March 1998, 1,282 patients in the HD9 trial were treated with either 8 cycles of COPP/ABVD, 8 cycles of BEACOPPbaseline, or 8 cycles of BEACOPPescalated. Between January 1999 and January 2003, 1,670 HD12 patients were randomized for two questions in a factorial design: first, for 8 cycles of BEACOPPescalated or "4+4", and second for consolidation RT or no RT to regions of initial bulk or residual disease. Patients with inadequate response or skeletal involvement were irradiated irrespective of randomized RT group based on the recommendation of a central diagnostic panel blinded to treatment groups. Results: In HD9-patients treated with COPP/ABVD, BEACOPPbaseline, and BEACOPPescalated, the 15-year progression-free survival (PFS) was 57%, 66.8%, and 74% with overall survival (OS) rates of 72.3%, 74.5%, and 80.9%, respectively. BEACOPPescalated remains significantly better than COPP/ABVD in terms of PFS (difference 17.0%; 95%-CI 8.3% to 25.6%) and OS (difference 8.6%; 95%-CI 1.4% to 15.7%) with consistent effects in subgroups by gender, IPS and ages up to 60 years. A total of 123 second malignancies corresponding to 15-year cumulative secondary malignancy incidences of 7.2%, 13%, and 11.4% were reported for COPP/ABVD, BEACOPPbaseline, and BEACOPPescalated, respectively, without a difference between COPP/ABVD and BEACOPPescalated (p=0.5). Standardized incidence ratios (SIR) with 95%-CI showed elevation compared to the general German population in all groups: 2.0 [1.2 to 3.2], 2.6 [1.9 to 3.4] and 2.6 [1.9 to 3.4]. Regarding HD12, the 10-year PFS and OS rates in the two chemotherapy groups were not significantly different with 82.6% and 87.3% in the BEACOPPescalated group and 80.6% and 86.8% in the 4+4 group, respectively. After chemotherapy, 153 of 1,481 (10.3%) patients with complete information had an RT recommendation irrespective of group and 378 (25.5%) had neither bulk nor residual disease. Amongst the remaining 950 patients (64.1%) with bulk or residual disease, patients randomized to no RT showed a significantly inferior 10-year PFS of 83.5% compared to patients in the RT group (88.6%, difference -5.1%; 95%-CI,-9.9% to -0.4%, hazard ratio [HR] 1.47) and a trend towards inferior OS in no RT patients (RT 93%; no RT 90.2%; difference -2.7%; 95%-CI,-6.5% to 1%). Patients with residual lesions without RT had both an inferior PFS and OS as compared to patients with RT (as treated comparison: 10-year PFS RT 89.7%; no RT 83.4%; difference -6.3%; 95%-CI,-12.8% to -0.1%; 10-year OS RT 94.4%; no RT 88.4%; difference -6%; 95%-CI,-11.4% to -0.5%). 10-year cumulative incidence of second malignancies ranged between 6.4% (4+4) and 9.7% (BEACOPPescalated+RT) without a significant difference between pooled chemo- or radiotherapy groups. Conclusions: These long-term follow-up observations indicate an ongoing benefit of an intensive first-line therapy strategy for the PFS and OS of patients with newly diagnosed advanced stage HL. The observed OS benefit suggests an important role of consolidating RT for patients with newly diagnosed advanced stage HL. The OS benefit does not seem to be relevantly compromised by the incidence of second malignancies. Disclosures von Tresckow: Novartis: Consultancy, Other: travel grants, Research Funding; Takeda: Consultancy, Other: travel grants; Millenium: Consultancy. Engert:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

scholarly journals BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years

Blood ◽  
2017 ◽  
Vol 129 (4) ◽  
pp. 456-459 ◽  
Author(s):  
Maria Gavriatopoulou ◽  
Ramón García-Sanz ◽  
Efstathios Kastritis ◽  
Pierre Morel ◽  
Marie-Christine Kyrtsonis ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Probability ◽  
Final Analysis ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Study ◽  
Key Points ◽  
Probability Of Response

Key Points BDR is a chemotherapy-free, non-stem-cell–toxic regimen associated with high response rates and long-term remissions. The long-term safety profile of BDR is favorable, with high probability of response to reintroduction of rituximab-based regimens at relapse.

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