9th International Symposium on Hodgkin Lymphoma Highlights

9th ISHL Highlights published on November 4, 2013
9th International Symposium on Hodgkin Lymphoma Highlights
Cologne, Germany, October 12 –15, 2013

Andreas Engert, MD - Program Chair
Chairman, German Hodgkin Study Group
Professor for Internal Medicine, Hematology & Oncology
University Hospital of Cologne, Department of Internal Medicine, Köln, Germany

Abstracts from Select Poster Presentations


Video Highlights

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Overview of the 9th ISHL 2013
Andreas Engert, MD

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Key issues in early-stage HL
James O. Armitage, MD

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Brentuximab Vedotin
James O. Armitage, MD

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Long-term follow up and survivorship in patients with HL
Bruce D. Cheson, MD

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Aspects of risk-adaptive therapy in advanced-stage HL
Massimo Federico, MD

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Challenges in applying PET for early stage HL
Martin Hutchings, MD, PhD

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Prognostic markers from gene expression profiling in formalin-fixed paraffin-embedded tissues
Christian Steidl, MD

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Current trial data in the treatment of relapsed and refractory HL
Bastian von Tresckow, MD

Mechanisms of the Differentiation of "HRS" Cells in Classical Hodgkin Lymphoma
Schneider M,1 Brauninger A,2 Hansmann ML,3 et al.
1Insitute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany; 2University of Giessen, Institute of Pathology, Giessen, Germany; 3Senckenberg Institute of Pathology, University of Frankfurt, Frankfurt am Main, Germany

Although Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) are derived from preapoptotic germinal center (GC) B-cells, they have lost their B-cell phenotype and express markers and transcription regulators normally restricted to other hemopoietic lineages. This "dedifferentiation" of HRS cells is likely key for cHL pathogenesis; in recent years, several factors have contributed to this "dedifferentiation" including NOTCH1, MSC, and ID2. CEBPB and MYC are also factors of interest where subsequent analyses are necessary.

Response-Adapted Therapy of Stage III-IV Hodgkin Lymphoma Based on Interim FDG-PET Imaging: Early Results of US Intergroup S0816
Press O, Li H, Schoder H, et al.
Fred Hutchinson Cancer Research Center/University of Washington; Memorial Sloan Kettering Cancer Center, University of Arizona, University of Rochester, et al.

Advanced-stage Hodgkin lymphoma (HL) is usually treated in North America with ABVD chemotherapy, with an approximate cure rate of 70%. BEACOPPescalated cures more patients with advanced HL, but is little used in the US due to its perceived toxicity; in addition, the regimen often causes infertility. Recent studies suggest that "interim" FDG-PET imaging performed after two cycles of ABVD identifies patients who will not be cured with ABVD, allowing early escalation to BEACOPPescalated in high-risk patients. Both non-hematologic and hematologic toxicities were significantly greater in the BEACOPPescalated arm than in the ABVD arm, as expected. Response-adapted therapy with centralized interim PET review is highly feasible in an intergroup setting. Early outcomes appear favorable in PET2+ (according to Deauville score) patients.

Tailored Therapy in Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Interim PET/CT, ISRAELI H2 PROTOCOL: Preliminary Report on 317 Patients
Dann EJ,1 Bairey O,2 Bar-Shalom R,1 et al.
1Rambam Medical Center (MC); 2Haifa; Rabin MC, Petach Tileva, et al.

The aim of Hodgkin lymphoma (HL) therapy is to maximize response and minimize long-term toxicity. This multicenter ongoing study evaluates outcome of HL patients whose therapy is chosen according to baseline prognostic factors and is tailored based on PET/CT performed after 2 cycles of chemotherapy (ABVD and involved nodal radiation tailored depending on whether the patient presented with early favorable or unfavorable disease). Patients with classic HL (aged 18-60 years), stages I-IV, were eligible. To date, 344 patients have been enrolled. Conclusions at this time demonstrate that tailored therapy based on interim PET is feasible both in early and advanced disease. Further follow up and a larger cohort are necessary to draw conclusions regarding long-term toxicity of this personalized approach.

Phase 2 Study Everolimus for Relapsed/Refractory Classical Hodgkin Lymphoma
Johnston PB,1 Pinter-Brown L,2 Rogerio J,3 et al.
1Mayo Clinic, Rochester, Minnesota, USA; 2Geffen School of Medicine at UCLA, Los Angeles, California, USA; 3Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA, et al.

Novel treatment options are needed to improve outcomes in classic Hodgkin lymphoma (HL) that is refractory to or relapse after initial chemotherapy or subsequent high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT). To confirm the efficacy and safety of everolimus in relapsed/refractory classic HL, a multicenter, open label phase 2 study was conducted. Response was assessed every 2 weeks. The primary endpoint was overall response rate. In conclusion, the favorable efficacy, short time to response, and manageable safety profile in this relapsed/refractory classic HL population confirm previous results and support further studies of everolimus in the treatment of classic HL.

Brentuximab Vedotin as First-Line Salvage Therapy in Relapsed/Refractory Hodgkin Lymphoma
Chen R,1 Palmer J,1 Thomas S,1 et al.
1City of Hope, National Medical Center, Weill Cornell Medical College, New York, New York, USA

Brentuximab vedotin (BV), an antibody drug conjugate, selectively delivers monomethyl auristatin E to CD30+ lymphoma cells. In a pivotal phase II trial for relapsed/refractory Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT), BV demonstrated an overall response rate of 75% and a complete response rate of 34%. To examine outcomes of BV given prior to ASCT, data were retrospectively analyzed from a consecutive case-series of HL patients who received BV as salvage therapy; three patients received BV as salvage therapy. In conclusion, BV as first-line salvage therapy can produce adequate response rates, has acceptable toxicity, and does not adversely impact stem cell collection or post-ASCT engraftment.

Acute Pulmonary Toxicity of Bleomycin-Incidence and Risk Factors in a Series of Hodgkin Lymphoma (HL) Patients Treated in a Single Center
Santos J,1 Carvalho S,1 Esteves S,1 et al.
1Instituto Portugues de Oncologia de Lisba Francisco Gentil, Portugal

Bleomycin may cause acute pulmonary toxicity (BPT) with potentially irreversible consequences on lung function and impact upon treatment continuation. Epidemiological and treatment factors (sex, age, G-CSF, smoking, previous lung disease) may increase the risk of BPT. The aim of this retrospective study was to evaluate the incidence, risk factors, and clinical course of BPT in patients with Hodgkin lymphoma (HL) receiving ABVD. BPT was defined as 1) clinical and imagiologic pneumonitis, without an infectious cause, and with a decreased lung diffusion capacity, or 2) at least one of the above criteria, leading to bleomycin discontinuation and/or treatment with corticosteroids. Sixty-five patients were analyzed. In conclusion, the incidence of BPT was similar to previous reports – moderate-to-severe in 25% of patients, leading to a change in treatment in 56% of patients. In this series, BPT was more frequent in women, with an increasing incidence with age. Prospective studies are needed with a larger patient population to identify the population at risk.


First-line Treatment of Advanced Stage Hodgkin Lymphoma. Final Results of Systemic Review and Network Meta-Analysis
Borchmann P,1 Rancea M,2 Skoetz N,2 et al. 1Department of Internal Medicine, Center of Integrated Oncology Koln Bonn, University Hospital of Cologne, Cologne, Germany; 2Cochrane Haematological Malignancies Group, Department of Internal Medicine, University Hospital of Cologne, Cologne, Germany, et al.

Hodgkin lymphoma in advanced stages can nowadays be cured with different combined modality approaches, but the debate whether BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) escalated or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) is superior is still ongoing. With regard to the most important outcome overall survival, no high-level evidence supporting one or the other strategy exists. The aim of this study was to assess the efficacy (OS) of different first-line treatment strategies compared to standard ABVD. This network analysis of different first-line treatment strategies for patients has shown meaningful benefit OS for first-line treatment with 6 cycles BEACOPP escalated over standard ABVD. Thus, BEACOPP escalated represents the gold standard of care for advanced stage Hodgkin lymphoma patients.

Frontline Therapy with Brentuximab Vedontin Combined with ABVD or ABV in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma
Ansell SM,1 Connors JM,2 Park SI,3. et al.
1Mayo Clinic, Rochester, Minnesota, USA; 2Cancer Agency Center for Lymphoid Cancer, Vancouver Canada; 3University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, et al.

The regimen ABVD is a common standard of care for the front-line treatment of Hodgkin lymphoma. A phase I, open-label multicenter study evaluating the safety of brentuximab vedotin administered in combination with standard therapy (ABVD) or a modified standard (AVD) in patients with advanced stage Hodgkin lymphoma. The safety profile confirmed that brentuximab vedotin may be safely combined with AVD; however, combination, with a bleomycin-containing regimen is contraindicated due to the incidence of pulmonary toxicity. Brentuximab vedotin 1.2 mg/kg every two weeks combined with AVD resulted in CR rates at the end of frontline therapy that compare favorably with historically reported results. A phase 3 study comparing brentuximab vedotin plus AVD versus ABVD alone is ongoing.

Impact of Bleomycin and Dacarbazine within the ABVD Regimen in the Treatment of Early Stage Favorable Hodgkin Lymphoma: Final Results of the GHSG HD13 Trial
Behringer K,1 Georgen H,1 Borchmann P,1 et al.
1German Hodgkin Study Group (GHSG), Department of Internal Medicine I, University Hospital of Cologne, Germany, et al.

Combined modality treatment consisting of two cycles of ABVD followed by involved-field radiotherapy (IFRT) is regarded as standard of care for early stage favorable Hodgkin lymphoma. However, the impact of bleomycin and dacarbazine in this combination has been questioned for many years. The GHSGHD13 trial compared two cycles of ABVD with a dacarbazine-deleted variant (AVB), a bleomycin-deleted variant (AVD) and a variant in which both dacarbazine and bleomycin (AV) were deleted. Results demonstrated that dacarbazine cannot be deleted from the ABVD regimen without a significant loss of efficacy. Whether bleomycin can be safely omitted from the regimen is under final analysis.

ABVD Therapy in Older Patients with Hodgkin Lymphoma: Response and Complications
Johnston PB,1 Yin J,2 McCallef INM1
1Mayo Clinic, Rochester, Minnesota, USA; 2Yangzhou, China

There is no consensus as to the optimal treatment for elderly patients diagnosed with Hodgkin lymphoma. An IRB approved review of the medical records of all patients diagnosed with Hodgkin lymphoma age 60 and over between 1996 and 2007 at the Mayo Clinic in Rochester, Minnesota. Complete and partial remission rates in patients treated with ABVD-based regimens were 69% and 17%, respectively. Three-year OS and PFS was 66% and 64%, respectively. Lung toxicity was the most common toxicity, with neutropenia and neuropathy also being quite frequent. Cardiac toxicity only occurred in 11% of patients receiving ABVD. Elderly patients with Hodgkin lymphoma can have high response rates with ABVD, but have a high incidence of pulmonary complications, therefore, the selection of treatment must be individualized based on patient comorbidities.

Clinical Significance of Tumor-Associated Macrophages in Early Stage Hodgkin Lymphoma
Gotti M,1 Nicola M,2 Fiaccadori V,1 et al.
1Department of Hematology Oncology, Fondazzione IRCCS Policlinico San Matteo & University of Pavia, Pavia, Italy; 2 Department of Human Pathology, Fondazzione IRCCS Policlinico San Matteo & University of Pavia, Pavia, Italy

Although patients with early stage Hodgkin lymphoma have a high cure rate, a proportion of them is resistant to or relapse after standard treatment and current prognostic data do not allow an accurate identification of those patients with a less favourable clinical outcome. In a recent study, an increased number of tumor-associated macrophages was found to have a strong correlation with shortened survival in patients with classic Hodgkin lymphoma. The aim of the study was to evaluate the clinical significance of the proportion of CD-68 positive infiltrating macrophages in patients with early stage Hodgkin lymphoma. Findings suggest that a proportion of CD-68 positive infiltrating macrophages greater than 25% is associated with unfavourable clinical outcome in patients with early stage Hodgkin lymphoma.

Plasma MicroRNA are Disease Response Biomarkers in Classical Hodgkin Lymphoma
Jones K,1,2 Nourse JP,1 Keane C,1-3 et al.
1Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia; 2Experimental Haematology Laboratory, School of Medicine, University of Queensland, Translational Research Institute, Brisbane, Australia; 3Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia

In classical Hodgkin lymphoma, Hodgkin-Reed Sternberg cells are sparse, embedded within a benign tumour microenvironment that has a distinct composition from the healthy lymph nodes. MicroRNA shows considerable potential as tissue biomarkers in classical Hodgkin lymphoma, however, the role of MicroRNA as circulating cell-free disease response biomarkers remains untested. Results of prospective tests demonstrated that circulating cell-free MicroRNA can reflect disease response once therapy has commenced. The combination of MicroRNA and protein biomarkers should be tested in large prospective cohorts as disease response biomarkers during first-line therapy for classical Hodgkin lymphoma.
Last modified: December 12, 2013

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