Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma

Bröckelmann, Paul J.; Müller, Horst; Casasnovas, Olivier; Hutchings, Martin; Tresckow, Bastian von; Jürgens, Mikkel; McCall, Susan J.; Morschhauser, Franck; Fuchs, Michael; Borchmann, Peter; Moskowitz, Craig H.; Engert, Andreas

doi:10.1093/annonc/mdx072

Cited by 85 publications

(64 citation statements)

References 11 publications

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“…Approximately 45–55% of the transplanted patients are cured (5–7). Long term PFS is dependent upon prognostic factors determined prior to salvage chemotherapy (20, 28, 29), but more importantly, response to this chemotherapy whether complete or partial is the focal point in predicting outcome.…”

Section: Interim 18f-fluorodeoxyglucose-positron Emission Tomography mentioning

confidence: 99%

“…It has been shown in several analyses that patients with certain adverse prognostic factors at recurrence have a poor prognosis even with HDCT (see also chapter 3 “Prognostic factors in Hodgkin Lymphoma” in this issue) (20, 28, 29). Especially the prognosis of patients with primary refractory disease is dismal with previously reported 5-year OS rates of 30% or less.…”

Section: Consolidation After High Dose Chemotherapy (Hdct)mentioning

confidence: 99%

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Treatment of relapsed and refractory Hodgkin Lymphoma

Tresckow

Moskowitz

2016

Seminars in Hematology

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Despite the high first line cure rates in patients with Hodgkin Lymphoma (HL) still 10–20% of patients suffer from relapsed or refractory disease. High dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is standard of care for suitable patients with relapsed or refractory HL and allows for cure in approximately 50%. Due to the poor prognosis of high risk patients even with HDCT and ASCT, consolidation strategies have been evaluated to improve the cure rates. For patients with recurrence after HDCT and ASCT, treatment is palliative in most cases. The anti CD30 antibody-drug conjugate brentuximab vedotin (BV) has been shown to induce high response rates in these patients; however, durable responses were reported in a small percentage of patients only. For carefully selected patients with multiple relapses, dose-reduced allogeneic transplant (RICallo) is a potentially curative option. The role of RICallo will have to be reevaluated in the era of anti-programmed death-1 (PD1) antibodies.

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Section: Interim 18f-fluorodeoxyglucose-positron Emission Tomography mentioning

confidence: 99%

Section: Consolidation After High Dose Chemotherapy (Hdct)mentioning

confidence: 99%

Treatment of relapsed and refractory Hodgkin Lymphoma

Tresckow

Moskowitz

2016

Seminars in Hematology

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“…In addition, there was considerable disease control also in patients with active disease, including CRs especially among cHL patients. [80] This cellular approach could constitute a promising option, especially applied consolidative in patients with high-risk disease [81] who undergo ASCT for rrHL. Nevertheless, refinement of technical engineering, dosing, conditioning, and methods to overcome the immunosuppressive microenvironment remain to be addressed by future research.…”

Section: Cellular Therapymentioning

confidence: 99%

“…Adequate risk stratification and respective intensification or de-escalation of therapy in patients eligible for intensive therapy in rrHL according to prognostic groups should be pursued with these novel agents. [81] Besides consolidation with BV after ASCT, [55] checkpoint inhibitors and/or CARTs might constitute an additional option for patients at high risk for consecutive relapse. The promising but preliminary results with different approaches commence an exciting time of immunotherapy in HL.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Current and future immunotherapeutic approaches in Hodgkin lymphoma

Bröckelmann

Borchmann

Engert

2016

Leukemia & Lymphoma

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Hodgkin lymphoma (HL) has become a highly curable malignancy even in advanced stages when treated adequately. However, relapsed or refractory disease and treatment-related toxicity constitute a significant clinical challenge. Innovative approaches are thus needed to improve treatment of these mainly young patients. In HL lesions, very few malignant Hodgkin and Reed-Sternberg (HRS) cells are embedded in an immunosuppressive microenvironment of reactive cells. Novel approaches such as bispecific antibodies, antibody-drug conjugates, immune-checkpoint inhibitors or adoptive cellular therapies are currently being investigated with promising results in relapsed or refractory patients. Encouraging response rates and a favorable toxicity profile have recently been reported in early phase clinical trials with antibodies blocking the programed-death receptor 1 (PD1). This review will summarize the current clinical knowledge on mechanism, safety and efficacy of the different agents and discuss potential future strategies, which are partly already investigated within clinical trials.

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“…Patients with classical Hodgkin lymphoma (cHL) who relapse or progress after autologous stem cell transplantation (auto‐SCT) have a dismal prognosis. Advanced stage and/or extranodal involvement and B‐symptoms at relapse as well as duration of remission <12 months are associated with negative outcome . Until a few years ago, therapeutic options were limited and included conventional chemotherapy, irradiation, and allogeneic SCT (allo‐SCT).…”

Section: Introductionmentioning

confidence: 99%

Positive impact of brentuximab vedotin on overall survival of patients with classical Hodgkin lymphoma who relapse or progress after autologous stem cell transplantation: A nationwide analysis

Tsirigotis

Vassilakopoulos²,

Batsis

et al. 2018

Hematological Oncology

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The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after autologous stem cell transplantation (auto-SCT) is poor. Recently, the anti-CD30 monoclonal antibody-drug conjugate, brentuximab vedotin (BV), has shown remarkable activity in the setting of R/R cHL. In the pivotal phase II study, BV produced an overall response rate of 75% and a median progression-free survival of 6.7 months. Although these results have been reproduced by large registry studies, the impact of BV on the overall survival (OS) of patients with R/R cHL has not been addressed so far. The aim of this study was to examine the impact of BV on OS in the setting of post auto-SCT R/R cHL. Analysis was performed in a group of patients with R/R cHL after a previous auto-SCT reported in the Greek registry during the last 2 decades. By using a multivariate model and censoring patients at the time of subsequent allo-SCT or treatment with immune checkpoint inhibitors, we showed that treatment with BV in the posttransplant relapse setting has a positive impact on the outcome and results in significant improvement of OS. To our knowledge, this the first published study, addressing the impact of BV on the OS in the setting of posttransplant relapse.

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Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma

Abstract: GHSG HD10 NCT00265018, HD11 NCT00264953, HD12 NCT00265031, HD13 ISRCTN63474366, HD14 ISRCTN04761296, HD15 ISRCTN32443041 and HDR2 NCT00025636.

Cited by 85 publications

References 11 publications

Treatment of relapsed and refractory Hodgkin Lymphoma

Treatment of relapsed and refractory Hodgkin Lymphoma

Current and future immunotherapeutic approaches in Hodgkin lymphoma

Positive impact of brentuximab vedotin on overall survival of patients with classical Hodgkin lymphoma who relapse or progress after autologous stem cell transplantation: A nationwide analysis

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