scholarly journals Treatment of Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Subgroup Analysis of the Randomized German Hodgkin Study Group HD16 Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2439-2439
Author(s):  
Dennis A. Eichenauer ◽  
Ina Bühnen ◽  
Michael Fuchs ◽  
Helen Kaul ◽  
Carsten Kobe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hodgkin Lymphoma ◽  
Growth Pattern ◽  
Research Funding ◽  
Early Stage ◽  
Stage Ii ◽  
Study Group ◽  
Stage Ib ◽  
Consolidation Radiotherapy ◽  
Support Research

Abstract Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for approximately 5% of all Hodgkin lymphoma (HL) cases. Pathological and clinical characteristics differ from classical HL (cHL). In contrast to cHL, the malignant cells in NLPHL are consistently positive for CD20 but stain negative for CD30. The clinical course of NLPHL is usually indolent and patients present with early-stage disease more frequently than in cHL. Patients and Methods: We investigated characteristics and outcomes of 85 patients with NLPHL (stage IB and stage II without risk factors) who had treatment within the randomized German Hodgkin Study Group HD16 study for early-stage HL. Results were compared to those from 495 cHL patients (stage IB and stage II without risk factors) treated within the same study. Patients were randomized between standard treatment consisting of 2 cycles of ABVD followed by consolidation radiotherapy and treatment guided by interim positron emission tomography after 2 cycles of ABVD (PET-2). PET-2-guided treatment consisted of 2 cycles of ABVD alone for patients with a negative PET-2 and 2 cycles of ABVD followed by consolidation radiotherapy for patients with a positive PET-2 (defined as a Deauville score ≥ 3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method including 95%-confidence intervals (95%-CI) and hazard ratios (HR) obtained from Cox regression models. Analyses were performed descriptively. Results: Overall, 62/85 NLPHL patients (73%) were male as compared to 254/495 cHL patients (51%) (p=0.0002). The median age was 37 years (range: 19-71 years) among patients with NLPHL and 36 years (range: 18-75 years) among patients with cHL (p=0.4380). Information on the histopathological growth pattern was available for 67/85 NLPHL patients of which 44 (66%) had a typical growth pattern. The PET-2 was positive in 39/85 NLPHL patients (46%) and in 171/495 cHL patients (35%) (p=0.0507). After a median observation time of 64 months, the 5-year PFS was 90.3% (95%-CI: 83.8-96.7%) for all 85 NLPHL patients and 90.8% (95%-CI: 88.1-93.5%) for all 495 cHL patients (HR=1.1; 95%-CI: 0.5-2.1). The 5-year PFS rates for PET-2-positive NLPHL (n=39) and cHL (n=171) patients were 89.3% (95%-CI: 79.4-99.2%) and 91.6% (95%-CI: 87.2-96%) (HR= 1.3; 95%-CI: 0.5-3.5), respectively. The 5-year PFS rates for PET-2-negative NLPHL (n=46) and cHL (n=324) patients were 91% (95%-CI: 82.7-99.4%) and 90.4% (95%-CI: 87-99.4%) (HR=0.85; 95%-CI: 0.3-2.4), respectively. PET-2-negative NLPHL (n=25) and cHL (n=152) patients treated with 2 cycles of ABVD alone had 5-year PFS rates of 83% (95%-CI: 67.8-98.2%) and 88.2% (95%-CI: 82.7-93.6%) (HR=1.5, 95%-CI: 0.5-4.5), respectively. In contrast, PET-2-negative NLPHL (n=21) and cHL (n=172) patients treated with 2 cycles of ABVD followed by consolidation radiotherapy had 5-year PFS rates of 100% and 92.3% (95%-CI: 88.1-96.5%) (HR=0; 95%-CI: 0), respectively. NLPHL patients with a typical growth pattern (n=44) had a 5-year PFS of 95.2% (95%-CI: 88.8-100%) whereas patients with an atypical growth pattern (n=23) had a 5-year PFS of 82.2% (95%-CI: 66.3-98%) (HR=2.5; 95%-CI: 0.5-11.2). A total of 9 NLPHL patients experienced disease progression or relapse during follow-up. The median time to NLPHL recurrence was 14 months (range: 1-89 months). There were 2 cases of second primary malignancies (1 case of malignant melanoma, 1 case of stomach cancer) among patients with NLPHL. No patient developed histological transformation into aggressive B-cell non-Hodgkin lymphoma. The 5-year OS rates were 100% and 98.6% (95%-CI: 97.5-99.7%) (HR=0; 95%-CI: 0) for patients with NLPHL and cHL, respectively. Conclusion: Taken together, the 5-year outcomes for patients with newly diagnosed early-stage NLPHL were similar to their counterparts with cHL. Thus, the current standard of care for early-stage cHL consisting of 2 cycles of ABVD followed by consolidation radiotherapy represents a highly active option also for the treatment of patients with the initial diagnosis of stage IB and stage II NLPHL without risk factors. Disclosures Fuchs: Takeda: Consultancy, Honoraria; Lukon: Honoraria; Celgene: Honoraria; BMS: Honoraria; MSD: Honoraria. von Tresckow: AstraZeneca: Honoraria, Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Pentixafarm: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Engert: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy; MSD: Honoraria; Hexal: Honoraria.

scholarly journals Efficacy and Safety of Nivolumab and AVD in Early-Stage Unfavorable Hodgkin Lymphoma: Extended Follow-up from the GHSG Phase II Nivahl Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Paul J Bröckelmann ◽  
Helen Goergen ◽  
Ulrich Keller ◽  
Julia Meissner ◽  
Karolin Trautmann ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Early Stage ◽  
Corticosteroid Treatment ◽  
Primary Analysis ◽  
For Profit ◽  
Health Care Company ◽  
Support Research

Background The primary analysis of the investigator-sponsored randomized multicenter phase II GHSG NIVAHL trial showed feasibility and excellent short-term efficacy of anti-PD1 based 1st-line treatment of early-stage unfavorable classical Hodgkin lymphoma (cHL). Achieving long-term disease control without excessive treatment-related morbidity is of utmost importance when developing innovative 1st-line cHL therapies. Duration of response and development of persisting immune-related toxicities are of concern in the setting of 1st-line anti-PD1 treatment. Methods NIVAHL enrolled treatment naïve early-stage unfavorable cHL patients at 28 German centers and individuals were randomized to either receive fully concomitant 4x Nivo-AVD (group A) or sequential 4xnivolumab, followed by 2x Nivo-AVD and 2x AVD (group B). Both groups received consolidative 30Gy IS-RT and the primary endpoint was complete response (CR) rate at end of study treatment. Detailed methods, patient characteristics and the primary endpoint analysis of NIVAHL have been recently published (Bröckelmann PJ et al. JAMA Oncol 2020). Herein we present extended follow-up of the NIVAHL trial to assess efficacy in terms of 2-year progression-free (PFS) and overall survival (OS) as well as safety with regards to long-term toxicities or organ impairment documented during the first year of follow-up after treatment. Results A total of 109 patients with cHL confirmed by central pathology review were enrolled between 04/2017 - 10/2018 and followed for a median of 20 and 21 months in groups A (n=55) and B (n=54), respectively, for the present analysis. All of the 7 patients deemed in partial remission (PR) at end of study treatment (EOT) converted into an ongoing CR after end of study without additional treatment during follow-up. With no relapse and no death observed since the primary analysis, the 2-year PFS estimates are 100% and 98% (95%CI 88-100%) in groups A and B, respectively, and the 2-year OS is 100% in both groups. With a median observation time for late-toxicities of 14 months after EOT (range 6-26 months) among 103 patients, any potentially treatment-related AE during follow-up was reported in 65% of patients (A: 74%, B: 56%). The highest documented CTCAE grade of late AEs was °I in 33%, °II in 25% and °III in 7% of patients with no °IV-V AEs observed. A total of 54% had at least one late event related to AVD, 47% to nivolumab and 32% to RT, with multiple relations attributable per event. Mean FEV1 and DLCOc did not decrease from baseline (91.1% -> 96.4% and 86.2% -> 83.3%, respectively). Decreased LVEF after EOT was reported in 2/56 patients with available data (4%). After EOT, 18% of patients required medication for adverse events. Corticosteroid ≥ and < 10mg prednisolone equivalent was required in 3% and 2% of patients, respectively, for a toxicity at any time during follow-up. No patient required corticosteroid treatment at last available follow-up. Most frequent toxicities reported after EOT included fatigue (21%), hypothyroidism (17%), respiratory tract disorders (16%), leukopenia (14%) and nervous system disorders (14%). Hypothyroidism was the event most frequently solely attributed to nivolumab during follow-up. The median time to onset after EOT was 5 months and affected patients nearly exclusively female (15/16 [94%]). After median follow-up of 10 months (range 0-21), hypothyroidism remained unchanged in 10 of 16 affected patients and resolved in 3 patients. Conclusion The excellent disease control of concomitant and sequential nivolumab and AVD in early-stage unfavorable cHL is confirmed with the currently available follow-up. Treatment-related toxicities ongoing or emerging during follow-up are predominantly associated with chemo- and/or RT. The most frequent nivolumab-associated late toxicity is hypothyroidism. No patient currently requires chronic corticosteroid treatment. Disclosures Bröckelmann: Bristol Myers Squibb: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; MSD Sharp & Dohme: Research Funding. Keller:Bristol Myers Squibb: Honoraria, Other: Travel support, Speakers Bureau. Meissner:Celgene: Other: Travel support; Bristol Myers Squibb: Other: Travel support; Takeda: Other: Travel support; Merck Sharp & Dohme: Other: Travel support; Hexal: Other: Travel support. Trautmann:Bristol Myers Squibb: Honoraria. Kerkhoff:BMS: Honoraria. Hüttmann:Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Lead Discovery Center GmbH: Consultancy; Seattle Genetics: Research Funding; Gilead: Honoraria; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Roche: Other: Travel expenses; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Zimmermann:Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb: Other: Travel Expenses; MSD: Other: Travel Expenses; Novartis: Other: Travel Expenses. Fuchs:Bristol Myers Squibb: Honoraria, Research Funding; Affimed: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria. von Tresckow:Takeda: Honoraria, Other: Travel support, Research Funding; Novartis: Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; MSD Sharp & Dohme: Honoraria, Research Funding; Roche: Honoraria; Kite/Gilead: Honoraria; Pfizer: Honoraria; Amgen: Honoraria. Borchmann:Takeda: Research Funding; Bristol Myers Squibb: Research Funding. Engert:Bristol Myers Squibb: Honoraria, Research Funding; Affimed Therapeutics: Research Funding; Takeda: Honoraria, Research Funding; MSD Sharp & Dohme: Honoraria; AstraZeneca: Honoraria; Sandoz: Honoraria. OffLabel Disclosure: Nivolumab 240mg Q2W alone or in combination with AVD for 1st-line treatment of classical Hodgkin lymphoma.

scholarly journals PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 By the German Hodgkin Study Group

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 925-925 ◽  
Author(s):  
Michael Fuchs ◽  
Helen Goergen ◽  
Carsten Kobe ◽  
Hans Eich ◽  
Christian Baues ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Early Stage ◽  
Phase 3 ◽  
Advisory Committees ◽  
Deauville Score ◽  
To Receive ◽  
Support Research

Abstract Background. Combined modality treatment (CMT) consisting of two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and 20 Gy of involved-field radiotherapy (IFRT) is widely accepted standard of care for early-stage favorable Hodgkin lymphoma (HL). Recent clinical research suggests that metabolic response assessment after two cycles of chemotherapy using FDG-PET (PET-2) can predict the individual outcome and PET-2 negativity might allow reducing the overall treatment intensity. Aims. We assessed whether omitting consolidating radiotherapy in patients with negative PET-2 is feasible without loss of efficacy as determined by progression-free survival (PFS). Furthermore, we analyzed the prognostic impact of PET-2 among patients receiving CMT. Methods. Between November 2009 and December 2015, we recruited patients with newly diagnosed, early-stage favorable HL aged 18-75 years from Germany, Switzerland, Austria, and the Netherlands for this double-blind, randomized, parallel-group phase 3 trial. Patients were randomly assigned to receive standard CMT with 2x ABVD and 20 Gy IFRT or PET-guided treatment, whereby IFRT was restricted to those patients with a positive PET after 2xABVD. PET-2 was centrally assessed by a panel blinded towards the randomization result, with FDG uptake not higher than the mediastinal blood pool (i.e., Deauville score 1-2) defined as negative. The trial was designed to exclude inferiority of 10% or more in 5-year PFS of ABVD only compared with CMT in a per-protocol analysis among PET-negative patients, corresponding to a non-inferiority margin of 3.01 for the hazard ratio, and to detect a 5-year PFS difference of 5% or more between PET-2-positive and -negative patients receiving CMT, each with 80% power. Results. A total of 1150 patients were enrolled; 628 patients with negative PET-2 were eligible for the per-protocol non-inferiority analysis and were treated with CMT (n=328) or ABVD alone (n=300). With a median follow-up of 47 months, the estimated 5-year PFS was 93.4% (90.4-96.5) with CMT and 86.1% (81.4-90.9) with chemotherapy only (difference 7.3%, 95% CI 1.6%-13.0%). The hazard ratio was 1.78 with a 95% CI ranging from 1.02 to 3.12, including the non-inferiority margin of 3.01. The PFS difference primarily resulted from a significant increase in disease recurrences with in-field recurrence rates of 2.1% vs. 8.7% (p=0.0003); there was no relevant difference regarding out-field recurrences (3.7% vs. 4.7%, p=0.55). Estimated 5-year overall survival in the per-protocol population was 98.1% (96.5-99.8) with CMT and 98.4% (96.5-100.0) with ABVD. 693 patients assigned to receive CMT were eligible for the analysis of the PET objective and had a negative (n=353) or positive (n=340) PET-2. With a median follow-up of 46 months, estimated 5-year PFS was 93.2% (90.2-96.2) among PET-2-negative and 88.1% (83.8-92.3) among PET-2-positive patients (p=0.035). When using the more common liver cutoff (Deauville score 4) for the definition of PET-2 positivity, the difference was more pronounced (5-year PFS 93.1% [90.7%-95.5%] vs. 80.1% [71.2%-88.9%], p=0.0004). Conclusion. In early-stage favorable HL, radiotherapy cannot be safely omitted from standard CMT without a clinically relevant loss of tumor control in patients with negative PET-2. PET positivity after 2xABVD represents a risk factor for PFS in HL patients treated with standard CMT, particularly when a Deauville score of 4 is considered as cutoff for positivity. Disclosures Greil: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Sandoz: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. von Tresckow:MSD: Honoraria, Other: Travel support, Research Funding; Novartis: Honoraria, Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding. Borchmann:Novartis: Consultancy, Honoraria.

scholarly journals Nivolumab and AVD for Early-Stage Unfavorable Hodgkin Lymphoma (NIVAHL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 236-236 ◽  
Author(s):  
Paul J Bröckelmann ◽  
Helen Goergen ◽  
Ulrich Keller ◽  
Julia Meissner ◽  
Rainer Ordemann ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Progressive Disease ◽  
Risk Group ◽  
Early Stage ◽  
Line Treatment ◽  
Classical Hodgkin Lymphoma ◽  
Group A ◽  
Group B ◽  
Support Research

Background The anti-PD1 antibody nivolumab is approved for relapsed or refractory classical Hodgkin lymphoma (cHL) showing high overall response rates (ORR) and a favorable safety profile. However, complete response (CR) is rare in this setting, and most patients develop progressive disease. To evaluate the efficacy of combined nivolumab and doxorubicin, vinblastine and dacarbazine (AVD) as 1st-line treatment for early-stage unfavorable cHL, we conducted the GHSG NIVAHL trial. Methods NIVAHL is a prospective, randomized, investigator-sponsored single-stage phase II trial that enrolled treatment-naïve early-stage unfavorable cHL patients between 18 and 60 years at 35 German centers (NCT03004833). In arm A, patients received 240mg nivolumab and AVD at standard doses on day 1 and 15 of each 28-day cycle for a total of four cycles (4xNivoAVD). In arm B, the same treatment was administered sequentially, starting with 4x nivolumab in 2-weekly intervals, followed by 2xNivoAVD and 2xAVD. Both groups received 30Gy involved-site radiotherapy (IS-RT). Primary endpoint is the centrally reviewed PET/CT-based CR rate after completion of protocol therapy including IS-RT. 55 patients per group were enrolled in order to exclude a CR rate ≤80% with a power of 90% on a one-sided alpha level of 2.5% each. Secondary endpoints will be analyzed descriptively and include treatment-related morbidity (TRMorbidity), progression-free (PFS), overall survival (OS), response at interim and final restaging as well as patient-reported outcomes. Sequential biopsies, blood and microbiome samples were collected for correlative studies. Results Between 04/2017 and 10/2018, a total of 110 patients were enrolled with one patient disqualified due to alteration of HL diagnosis by central pathology review (N=109, group A n=55, group B n=54). The median age of the predominantly female patients (60%) was 27 years. Stage II was present in 95% of cases with ≥3 involved areas as most common risk factor (69%), followed by elevated ESR (48%), large mediastinal mass (20%) and extranodal disease (13%). Mean duration of chemoimmunotherapy was 15 (standard deviation (SD) 3) weeks and 22 (SD 6) weeks with a mean relative dose intensity of 87.4 (SD 15.9)% and 85.8 (SD 24.2)% in groups A and B, respectively. Severe protocol deviations occurred in 4 patients in group A and 5 in group B. Reasons were toxicity (n=5), patient's wish (n=2), incorrect allocation to early-stage unfavorable risk group (n=1) and progressive disease (n=1). Another 2 patients refused to receive IS-RT. Any adverse events (AEs) were reported for 98% of patients. AEs ≥°3 were observed in 73% and 78%, respectively, and serious AEs occurred in 38% and 28% of patients in groups A and B, respectively. TRMorbidity defined as organ toxicity ≥°3 or anemia, thrombocytopenia or infection °4 was documented in 16% and 22% of patients; all of these were organ toxicities predominantly of liver and gastrointestinal tract, with 19/21 events occurring during the first 2 treatment cycles. Data on ongoing or late toxicities is limited by short follow-up. Until 07/2019, 4 cases of persistent hypothyroidism have been reported. At the 1st interim restaging after 2xNivoAVD and 4x nivolumab, the ORR was 100% (54/54) and 96% (49/51), with a CR rate of 85% and 53% in groups A and B, respectively. Interim remission status was not assessed in 1 and 3 patients, respectively, due to treatment discontinuation after incorrect allocation to early-stage unfavorable risk group (n=1) or toxicity (n=3). After completion of systemic therapy, ORR was 100% (54/54) and 98% (50/51) with a CR rate of 81% and 86%, respectively. One patient in group B developed histologically proven primary progressive HL during nivolumab monotherapy while no other case of progressive or relapsed disease or death has been documented so far. The centrally reviewed CR rate at the end of treatment will be reported at the meeting. Additionally, initial data from currently ongoing histopathologic and immunologic studies will also be presented. Conclusion Concomitant and sequential therapy with nivolumab and AVD is feasible with acceptable toxicity. In early-stage unfavorable cHL, concomitant Nivo-AVD induces a high early CR rate. The interim CR rate observed with 4x nivolumab monotherapy is higher than previously reported in relapsed or advanced-stage disease. The primary endpoint and initial PFS data will be reported at the meeting. Disclosures Bröckelmann: Bristol-Myers Squibb: Honoraria, Other: Travel Support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD Sharpe & Dohme: Research Funding. Kerkhoff:EUSA: Honoraria; Hexal: Honoraria; Celgene: Honoraria, Other: Travel Support; Roche: Honoraria; Novartis: Honoraria. Hüttmann:University Hospital Essen: Employment; Takeda: Honoraria; Gilead: Honoraria. Zimmermann:Takeda: Honoraria, Other: Travel Expenses; Novartis: Other: Travel Expenses; MSD: Other: Travel Expenses; BMS: Other: Travel Expenses. von Tresckow:MSD Sharpe & Dohme: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Roche: Honoraria; Amgen: Honoraria. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding. Borchmann:Novartis: Honoraria, Research Funding. OffLabel Disclosure: Nivolumab 240mg i.v. 2-weekly for 1st-line treatment of classical Hodgkin lymphoma.

Active Surveillance for Newly Diagnosed Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 654-654
Author(s):  
Sven Borchmann ◽  
Erel Joffe ◽  
Craig H. Moskowitz ◽  
Andrew D. Zelenetz ◽  
Ariela Noy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Active Surveillance ◽  
Research Funding ◽  
Management Strategy ◽  
Multivariate Model ◽  
Line Treatment ◽  
Secondary Cancers ◽  
Extranodal Disease

Abstract Background Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease. In the absence of consensus guidelines, treatment is controversial. Here, we describe the characteristics and outcomes of consecutive NLPHL patients diagnosed at Memorial Sloan Kettering Cancer Center (MSKCC) with a focus on active surveillance (AS) as a first-line management strategy. Methods We included consecutive patients aged 16 years (y) or older who were diagnosed and followed at MSKCC between 1974 and 2016. All cases were confirmed by a MSKCC hematopathologist as NLPHL without evidence of transformation. We excluded composite lymphomas and patients with any prior hematological malignancy or concomitant active cancer. We compared outcomes between patients followed expectantly (AS) and those treated actively (AT), which included radiotherapy (RT) only, chemotherapy (+/- Rituximab) (CT), combined modality (+/- Rituximab) (CMT), and rituximab monotherapy (R). Progression-free survival (PFS) was defined as time from diagnosis to a biopsy-proven disease progression or relapse, initiation of further treatment or death. PFS2 was defined as time from diagnosis to second biopsy-proven disease progression or relapse, initiation of 3rd-line treatment or death. AS was considered a 1st-line treatment. We used univariable and multivariable survival analyses stratifying patients by disease stage. Results In total, 163 patients were included. The median follow-up was 5.7y (Min-Max: 0.3 - 42.7) with 24.5% (n=40) of patients followed for 10y or more. Patient characteristics for all, AS and AT patients are shown in Table 1. Patients were treated with RT only (n=75, 46.0%), AS (n=37, 22.7%), CT (n=26, 15.9%), CMT (n=19, 11.7%) or R alone (n=6, 3.7%). Overall, outcome of patients was excellent, with 10-year PFS, PFS2 and overall survival (OS) estimates of 71.2% [95%-CI: 59.3-80.1], 92.5% [95%-CI: 83.7-96.6] and 96.6% [95%-CI: 87.6-99.1], respectively. Seven patients died, 3 deaths were likely treatment related and only one lymphoma related death occurred after progression. Twelve transformations to aggressive lymphomas occurred after a median of 7.0y (Min-Max: 0.4 - 15.6). The transformation rate was 0.99% per patient year. Twelve secondary cancers occurred after a median of 7.8y (Min-Max: 1.1 - 24.8). Only bulky disease ≥ 5 cm (n=21, HR: 3.1 [95%-CI: 1.3-7.2], p=0.008) and extranodal disease (n=11, HR: 7.7 [95%-CI: 2.1-28.5], p=0.002] were risk factors for a shorter PFS in the final multivariate model after correcting for received treatment. In pairwise comparison, PFS with CMT (p=0.038) and RT (p=0.032) was superior to AS, but CT was not (p>0.999). PFS2 and OS were not significantly different between groups. Patients, who received AT (n=126) overall tended to have superior PFS than those in the AS group (n=37) (5-year PFS 97.2% [95%-CI: 79.2-92.2] vs. 76.5% [95%-CI: 55.7-88.5], p=0.068), though this benefit was mainly seen in early stage disease (Ann Arbor I/II) (5-year PFS 94.2% [95%-CI: 86.7-97.6] vs. 65.1% [95%-CI: 43.5-80.2], p<0.001). This did not translate into better PFS2 (p=0.568) or OS (p=0.303) (Figure 1) and was confirmed in a multivariate model controlling for potential confounders that influenced the initial treatment decision. Comparing results in the AS and AT group, death occurred in 0 vs. 7 (0.0% vs. 5.6%), transformation in 2 vs. 10 (5.4% vs. 7.9%) and secondary cancers in 2 vs. 10 (5.4% vs. 7.9%) patients. Only 24.3% (n=9) of the 37 AS patients required treatment after a median of 5.1y (Min-Max: 0.3 - 23.2). Treatments after initial AS were localized radiation (n=4), R-CHOP (n=4) and R monotherapy (n=1) given for local symptoms (n=3), transformation (n=2), progressing nodes (n=2), systemic symptoms (n=1), adrenal insufficiency due to adrenal mass (n=1) and change of management strategy in stable disease (n=1). Conclusion NLPHL has an excellent prognosis. Bulky and extranodal disease were identified as potential risk factors for progression. With the limitations of a retrospective analysis, it can be concluded that AS is a viable management strategy in NLHPL. The majority of AS patients require no treatment after multiple years of observation and those that do, can be adequately managed with established treatments. Additionally, no evidence was found for an increased rate of transformation or worse PFS2 or OS in AS patients. Treatment related deaths exceeded deaths from lymphoma. Figure 1 Figure 1. Disclosures Moskowitz: Celgene: Consultancy; Genentech BioOncology: Consultancy; Seattle Genetics: Consultancy, Other: Ad Board, Research Funding; Merck: Consultancy, Research Funding; Pharmacyclics: Research Funding. Zelenetz: Genentech/Roche, GSK, Gilead, Celgene, Janssen, Hospira, Amgen, Takeda Pharma, Novartis, Nanostring Technologies, Portola Pharmaceuticals, Adaptive Biotechnology: Consultancy; GSK, Janssen, Roche, Gilead, Bristol Myers: Research Funding; Boehringer Ingelheim: Other: DMC Membership. Kumar: Seattle Genetics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Moskowitz: Incyte: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding; Takeda: Honoraria; ADC Therapeutics: Research Funding.

Treatment-Related Mortality in Patients With Advanced-Stage Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group

2013 ◽  
Vol 31 (22) ◽  
pp. 2819-2824 ◽  
Author(s):  
Diana Wongso ◽  
Michael Fuchs ◽  
Annette Plütschow ◽  
Beate Klimm ◽  
Stephanie Sasse ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hodgkin Lymphoma ◽  
Individual Risk ◽  
Tumor Control ◽  
Poor Performance Status ◽  
Study Group ◽  
Advanced Stage ◽  
German Hodgkin Study Group ◽  
Treatment Related Mortality ◽  
Related Mortality

Purpose The introduction of BEACOPPescalated (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPPescalated. Patients and Methods In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPPescalated-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Results Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPPescalated (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. Conclusion The individual risk of TRM associated with BEACOPPescalated can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

Fertility in Male Hodgkin Lymphoma Patients - A Report of German Hodgkin Study Group.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 101-101 ◽  
Author(s):  
Michal Sieniawski ◽  
Thorsten Reineke ◽  
Andreas Josting ◽  
Volker Diehl ◽  
Andreas Engert
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Sperm Count ◽  
Intermediate Stage ◽  
Treatment Evaluation ◽  
Study Group ◽  
The Third ◽  
Fertility Status ◽  
Evaluation Group ◽  
Pre Treatment

Abstract Purpose: We performed semen and hormone analysis before and after treatment to investigate the influence of disease and therapy on the fertility status of male patients with Hodgkin lymphoma (HL). Patients & Methods: Patients (pts) with first diagnosis of HL without previous chemotherapy or radiotherapy who were enrolled into trials of German Hodgkin Study Group (GHSG) between 1988 and 2003 were analyzed. 202 pts were evaluated prior to treatment and 112 pts were evaluated after treatment. Results: The median age in the pre-treatment evaluation group were 26 years and 27 years in the post-treatment evaluation group. In pre-treatment evaluation group 51% of pts were advance stage of disease, 31% in intermediate stage and 11% in early stage. In the post-treatment evaluation group 45% of pts were in intermediate stage of disease, 44% in advanced stage and 11% in early stage. Before treatment 20% (40/202) of pts had normozoospermia and 80% (162/202) had dyspermia. After treatment, 64% (72/112) of pts had azoospermia, 30% (33/112) other dyspermia and 6% (7/112), the differences are significant (p<0.001). Azoospermia was observed in 67% (62/93) of pts treated with combined modality, in 90% (9/10) of those treated with chemotherapy alone and in 11% (1/9) of those treated with radiotherapy alone (p<0.001). Azoospermia was more frequent after BEACOPP then after COPP/ABVD - 85% (34/40) vs. 63% (37/59) (p<0.001). There was no difference between patients treated with 8 cycles of BEACOPP escalated (n=15) and those treated with 8 cycles BEACOPP baseline (n=21); with 93% and vs. 86% (p>0.05). The median time of onset of spermatogenesis was 27 months. During the first year after the treatment the onset of spermatogenesis was found in 18% of pts, during the second year in 23%, during the third year in 35% and in 35% after the third year. In univariate risk factors analysis, we found exttranodal involvement, risk groups, treatment with chemotherapy and BEACOPP being significantly predictive for asevere damage of fertility, none of these factors was significant in multivariate analysis. In the contrast to the pre-treatment analysis, most of the pts (79%) showed abnormal FSH-levels (p<0.001). LH and testosterone were normal in most of patients; these results were similar to pre-treatment levels (p>0.005). There was the relationship between the post-therapeutic FSH level and sperm count; in the group with normal FSH levels, 23% of pts showed azoospermia and in the group with abnormal FSH level 78% of pts were azoospermic (p<0.001). The correlation between sperm count and LH and testosterone level was not so pronounced. Conclusion: The majority of patients with HL were azoospermic after treatment, but recovery of spermatogenesis was observed depending on the treatment received. The FSH level appears to be helpful in diagnosis of the fertility status.

scholarly journals PET-Based Response after 2 Cycles of Brentuximab Vedotin in Combination with AVD for First-Line Treatment of Unfavorable Early-Stage Hodgkin Lymphoma: First Analysis of the Primary Endpoint of Breach, a Randomized Phase II Trial of Lysa-FIL-EORTC Intergroup

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 736-736
Author(s):  
Luc-Matthieu Fornecker ◽  
Julien Lazarovici ◽  
Igor Aurer ◽  
Rene-Olivier Casasnovas ◽  
Anne-Claire Gac ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Trial ◽  
Early Stage ◽  
Brentuximab Vedotin ◽  
Primary Objective ◽  
Advisory Board ◽  
Advisory Committees ◽  
Grade 3

Abstract Background: About 15-20% of patients with early-stage unfavorable Hodgkin lymphoma (HL) relapse or are refractory to first-line treatment with combined modality therapies. Early assessment of metabolic response after 2 cycles of ABVD has been shown to be an accurate predictor of progression-free survival and overall survival. Brentuximab vedotin (BV) in combination with AVD chemotherapy (BV-AVD) has demonstrated a promising efficacy with a favorable safety profile in a phase I trial for treatment-naive patients (Younes A. et al, Lancet Oncol 2013). Based on these results, we conducted a randomized, multicentric, phase II trial in order to improve the PET response rate after 2 cycles with BV-AVD regimen for previously untreated, early-stage unfavorable Hodgkin lymphoma. Methods: Patients with previously untreated, stage I/II, HL and unfavorable EORTC/LYSA criteria (defined with at least one of the following: age ≥ 50 y, bulky mediastinal mass with mediastinum / thorax ratio ≥ 0.35, number of involved nodal areas ≥ 4, ESR ≥ 50mm/h or ≥ 30mm/h with B symptoms) were enrolled at the time of diagnosis. Patients were randomly assigned in a 2:1 ratio to receive 4 cycles of BV-AVD (experimental arm) or ABVD (standard arm), followed by 30Gy involved node radiation therapy (INRT). The primary objective was to evaluate the efficacy of the BV-AVD regimen, as measured by negative-PET rate after 2 cycles based on central review. PET was interpreted according to the Deauville 5-point scale with negative PET defined as Deauville 1-3. Patients with missing PET evaluation, whatever the reason, were considered as non-responders. The statistical hypothesis was based on an increase of 10% (from 75% to 85%) of the PET negativity rate after 2 cycles in the experimental arm. The standard arm was added in order to ensure that the hypothesis taken in the sample size evaluation (negative-PET rate after 2 cycles of ABVD ≤ 75%) was verified. If ≥ 93 patients out of 113 evaluable patients had negative-PET, the hypothesis that the negative-PET rate ≤ 75% in the experimental arm would be rejected. This planned analysis of the primary endpoint was performed by intention to treat (ClinicalTrials.gov registration: NCT02292979). Results: From March 2015 to October 2016, 170 patients were included, 113 were randomized in the BV-AVD arm and 57 in the ABVD arm. Median age at randomization was 29 y (range 18-60) and 51% were female. The median number of involved nodal areas was 3 and 92% of the patients were Ann Arbor stage II, 57% had a bulky disease and 40% had B symptoms. After 2 cycles of treatment, 93/113 patients (82.3%, 95% CI 75.3-88.0) and 43/57 (75.4%, 95% CI 64.3-84.5) achieved a negative-PET based on central review in the experimental and standard arms, respectively. With the lower bound of the 95% confidence interval superior to 75% in the experimental arm, the primary objective can be considered to be met. During the first 2 cycles, grade 3-4 adverse events (AEs) were documented in 74% of the patients in the BV-AVD arm and 56% in the ABVD arm. The most frequent grade 3-4 AEs in the experimental arm were neutropenia (64%), leucopenia (31%), gastro-intestinal disorders (8%), febrile neutropenia (7%), transaminases increased (4%) and infections (4%). Only 2 patients (2%) have developed a grade 3-4 peripheral neuropathy after the first 2 cycles of BV-AVD. No pulmonary toxicity has been observed. Grade 3-4 serious AEs (SAEs) were documented in 19% of the patients in the experimental arm (treatment-related SAEs in 17%) and 7% in the standard arm. SAEs have led to permanent BV discontinuation in 7/113 (6%) patients during the first 2 cycles. Reasons for permanent BV discontinuation were loss of weight, hyponatremia, febrile neutropenia, epileptic seizure, peripheral neuropathy, hepatitis and cutaneous rash. Conclusion: This randomized, multicentric, open-label phase II trial aimed to evaluate the efficacy of BV in combination with AVD chemotherapy based on PET response after 2 cycles for previously untreated, unfavorable early-stage HL. The primary objective was met with an improvement of the negative-PET rate with BV-AVD regimen. This first analysis highlighted an increased toxicity with BV-AVD regimen compared to ABVD, with a higher rate of grade 3-4 AEs and SAEs during the first 2 cycles of treatment. Disclosures Fornecker: BMS: Honoraria; Servier: Honoraria; Gilead: Honoraria; Roche: Honoraria; Takeda: Honoraria. Aurer: takeda: Honoraria, Research Funding. Bonnet: Takeda: Other: advisory board. Perrot: Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Amgen: Honoraria. Specht: Takeda: Other: advisory board. Touati: Takeda: Honoraria. Stamatoullas: Takeda: Consultancy; Celgene Corporation: Honoraria. Lugtenburg: Takeda: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Servier: Honoraria; Celgene: Honoraria; BMS: Honoraria; Sandoz: Honoraria. Federico: takeda: Honoraria, Research Funding. Andre: Takeda: Honoraria, Other: Advisory board, Research Funding.

scholarly journals Bleomycin Use in the Treatment of Hodgkin Lymphoma (HL): Toxicity and Outcomes in the Modern Era

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4038-4038
Author(s):  
Kekoa Taparra ◽  
Heshan Liu ◽  
Mei-Yin Polley ◽  
Kay M. Ristow ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hospital Admission ◽  
Hodgkin Lymphoma ◽  
Clinical Outcomes ◽  
Mayo Clinic ◽  
Research Funding ◽  
Treatment Strategies ◽  
Respiratory Therapy ◽  
Inclusion Criteria ◽  
Genetics Research

BACKGROUND: Historically, one in five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT), a life-threatening interstitial pneumonitis. The current treatment paradigm consists of prompt discontinuation of bleomycin, administration of corticosteroids, antibiotics, hospital admission, respiratory therapy, or intensive care. BPT represents a challenge for patients with HL as it not only impairs respiratory function, but also has negative impacts on clinical outcomes. A collection of a dozen studies suggest BPT has a mortality rate just short of 10% of patients who develop BPT. Given recent data on bleomycin omission with negative interim PET scan, we assessed changes in BPT rates and severity over the past 15 years. Overall, treatment protocol characterization and patient characteristics most responsive to BPT treatment are poorly understood. OBJECTIVES: In this study, we investigated the clinical impact and treatment strategies in patients with BPT. Our goals were to: 1) Identify HL patients in the last decades who developed BPT and identify risk factors for BPT, 2) evaluate the impact of BPT on long-term clinical outcomes, and 3) characterize patterns of treatment strategies among patients with HL who develop BPT. METHODS: A single-center, retrospective analysis was preformed using patient data from the Mayo Clinic Lymphoma Database (Rochester, MN) consisting of 1,299 patients diagnosed with HL. All patients were diagnosed between 2003-2018. Inclusion criteria included 1) newly diagnosed, biopsy proven HL, 2) upfront treatment with ABVD, 3) treatment was received at our institution. All patients were assessed for clinically relevant HL characteristics including stage of disease, presence of bulky disease, presence of B symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, BPT risk factors, and bleomycin treatment regimen. BPT was clinically defined as 1) Presence of pulmonary symptoms, 2) bilateral interstitial infiltrates on imaging, and 3) no evidence of infectious etiology. Patients treated in the "Early Era" (2000s) were compared to patients in the "Recent Era" (2010s). Comparison of continuous variables between BPT groups was assessed with Wilcox rank-sum test. OS and PFS were estimated via the Kaplan-Meier method. Approval of the protocol by the Mayo Clinic Institutional Review Board (IRB) was obtained and all patients were consented accordingly. RESULTS: One-hundred twenty six patients met the inclusion criteria for this study. Median follow-up for PFS and OS was 5.5 years (95%CI = 4.8-6.4) and 5.8 years (95%CI = 5.0-7.0), respectively. The 10-year OS and PFS among all patients were 85.1% (95%CI = 77.8-93.1) and 86.3% (95%CI = 80.1-93.0), respectively. Forty-seven patients (37% of all patients) met criteria for BPT. The estimated 10-year OS for BPT and non-BPT patients were 74.7% (95%CI = 61.8-90.5) and 91.7% (95%CI = 83.9-100.0), respectively. The estimated 10-year PFS for BPT and non-BPT patients were 84.7% (95%CI = 74.8-95.8) and 87.0% (95%CI = 79.1-95.8), respectively. In univariable analysis, BPT negatively impacted OS (HR=3.6, 95%CI: 1.2-10.6). However, bleomycin omission did not impact OS (HR=1.3, 95%CI=0.5-3.7). BPT-mortality was 17%. In multivariable analysis, BPT was not significantly associated with OS after adjusting for baseline characteristics (HR=3.0, 95%CI=0.9-9.9). Patients were older (median: 46 vs 33 years) and received less bleomycin (median: 107 vs 215 units) compared to non-BPT patients. BPT was most often managed with bleomycin omission with 59% of patients (74 of 126 patients) having omitted bleomycin at some point during treatment. Patients treated in the "Recent Era" (2010s) had lower BPT rates (28% vs 48%), mortality (10% vs 21%), bleomycin dose (143 vs 204 units), and bleomycin cycles (7 vs 12 cycles), yet higher prophylactic bleomycin omission (59% vs 8%) compared to "Early Era" (2000s). Patients treated in the Recent Era compared to Early Era had a reduction of BPT treatment with steroids, hospital admission, respiratory therapy, and ICU admission by 12%, 22%, 14%, 13%, respectively. CONCLUSION: Overall, our data suggests BPT continues to impact OS in HL patients treated with ABVD, however BPT treatment is decreasing as management changed in recent years. Disclosures Ansell: Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding.

scholarly journals Outcomes of Anti-PD1 Treatment for Relapsed/Refractory Hodgkin Lymphoma: A German Hodgkin Study Group (GHSG) Multi-Center Real-World Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4533-4533
Author(s):  
Jesko Momotow ◽  
Ina Bühnen ◽  
Karolin Trautmann-Grill ◽  
Guido Kobbe ◽  
Martin Wilhelm ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cause Of Death ◽  
Research Funding ◽  
Routine Care ◽  
Pivotal Phase ◽  
Safety And Efficacy ◽  
Best Response ◽  
Support Research

Abstract Background: Immune-checkpoint inhibition with antibodies targeting programmed death protein 1 (PD1) was well tolerable and highly effective in pivotal phase II and III trials in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL). We aimed to evaluate emerging therapeutic sequences and the safety and efficacy of anti-PD1 antibodies in the rapidly changing routine care of r/r cHL. Methods: GHSG-affiliated hemato-oncology departments and practices in Germany were invited to participate in this retrospective study. Patients ≥18 years of age receiving anti-PD1 antibodies for r/r cHL in routine care were eligible. Patient, disease and treatment characteristics were documented by the treating physicians with standardized case report forms. Locally assessed response rates were reported as complete (CR) or partial (PR) remission, stable (SD) or progressive (PD) disease and summarized as objective response rate (ORR: CR + PR). Progression-free (PFS) and overall survival (OS) were analyzed according to Kaplan-Meier from the start of anti-PD1 treatment in routine care to PD (PFS) or death from any cause (PFS + OS). All analyses were done descriptively and conducted in SAS V9.4. Results: A total of 58 r/r cHL patients (pts.) with a median age of 48 years (range 19-89 years) and male predominance (57%) initiated anti-PD1 treatment between 11/2014 and 01/2021 at 15 sites. Median time from 1 st-line to anti-PD1 treatment was 5.5 years (0.8-26.0). The majority had received prior brentuximab vedotin (BV, 86%) or an autologous stem-cell transplantation (autoSCT, 62%) and 16% undergone prior alloSCT. Relevant co-morbidities including HIV, pre-existing autoimmune conditions, cardiovascular diseases and dialysis-dependent kidney failure were documented in 49% of patients. An impaired ECOG performance status of ≥1 was present in 57% of patients (ECOG 2: 12%, ECOG 3: 4%). At initiation of anti-PD1 treatment, 74% of patients presented with stage III/IV disease and 35% did not achieve a response to their latest prior therapy. The median duration of anti-PD1 treatment was 18.1 (0.5-79.3) months and 50% of patients still received an anti-PD1 antibody at data collection. One third (31.6%) of patients experienced grade III/IV treatment-related toxicities and a treatment delay of >6 weeks due to toxicity occurred in 15.5% of patients. Investigator-assessed ORR was 66.7% with 20.4% of patients achieving a CR and 46.3% a PR as best response (Figure 1A). With a median follow-up of 19.1 (0-74.7) months and 26.7 (0-74.7) for PFS and OS, respectively, median PFS (mPFS) and OS were 12.3 months and 32 months, respectively (Figure 1B+C). Corresponding 2-year PFS and OS estimates were 38.3% (95%CI 24.4-52.2) and 78.5% (95%CI 67.2-89.8). Median PFS was more favorable in patients achieving either a CR (30.1 months) or PR (24.9 months) compared to SD (9.3) or PD (3.4, Figure 1D), with similar trends also observed for OS. Two thirds (67%) of the 29 patients eventually experiencing PD, continued anti-PD1 treatment beyond progression at least once, with a median duration of 9.9 (3.0-25.8) until 2 nd PD. Overall, 28% patients received concomitant add-on treatments with radiotherapy (62.5%) and chemotherapy (25%) administered simultaneously most commonly. Best response to combination treatment was PR in 84.6% and SD in 15.4% of patients, and 75% of patients receiving add-on treatments achieved their best response only thereafter. Most common consecutive treatments were allogeneic stem-cell transplantation (N=5), BV-based therapy (N=5), Gemcitabine-based regimens (N=4) radiotherapy (N=4) and N=13 patients did not receive further treatment after anti-PD1 failure. Most common cause of death was cHL (58% of deaths reported), followed by non-anti-PD1 treatment-related causes (16%), infections and cardiac diseases (11% each) and second neoplasms (5%). Conclusions: In this multicenter cohort of older and frailer r/r cHL patients receiving anti-PD1 antibodies in routine care, safety and efficacy data including ORR, mPFS and mOS was similar to data reported from pivotal phase II trials. Anti-PD1 treatment for r/r cHL thereby appears feasible and able to induce meaningful clinical benefit in a broad range of patients. Despite various concomitant and subsequent treatments administered, however, cHL or subsequent treatments are by far the leading cause of death. Failure of anti-PD1 in r/r cHL hence constitutes an unmet need. Figure 1 Figure 1. Disclosures Trautmann-Grill: GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Kobbe: Celgene: Research Funding. Heinrich: Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Eisai: Consultancy; Lilly: Consultancy, Research Funding; Sanofi: Consultancy; Astra: Consultancy, Research Funding; Abbvie: Research Funding. Schmidt: Incyte: Honoraria; Biotest: Honoraria; Alexion: Honoraria; AbbVie: Honoraria; Sanofi-Aventis: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Hüttmann: Celgene: Honoraria; Gilead: Honoraria; Lead Discovery Center GmbH: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fuchs: Lukon: Honoraria; Celgene: Honoraria; MSD: Honoraria; BMS: Honoraria; Takeda: Consultancy, Honoraria. von Tresckow: Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Kite-Gilead: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Takeda: Consultancy, Honoraria, Other, Research Funding; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Pentixafarm: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; AstraZeneca: Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support. Borchmann: Gilead Sciences: Honoraria; BMS/Celgene: Honoraria; Janssen: Honoraria; Miltenyi Biotech: Honoraria; Novartis: Honoraria. Engert: MSD: Honoraria; Hexal: Honoraria; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy. Bröckelmann: BMS: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; MSD: Research Funding; BeiGene: Research Funding.

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