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Hodgkin’s Disease an Update. Is more always better? Jeffrey Schriber, M.D. Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center.

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Presentation on theme: "Hodgkin’s Disease an Update. Is more always better? Jeffrey Schriber, M.D. Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center."— Presentation transcript:

1 Hodgkin’s Disease an Update. Is more always better? Jeffrey Schriber, M.D. Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center

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3 Statistics at a Glance Percent Surviving 5 Years 85.3% Percent Surviving 5 Years 85.3%

4 New Cases, Deaths and 5-Year Relative Survival Year Year Relative Survival 69.9%73.4%78.7%81.0%83.0%84.9%85.1%88.3%

5 Percent of New Cases by Age Group: Hodgkin Lymphoma Median Age At Diagnosis 39 Median Age At Diagnosis 39

6 Percent of Deaths by Age Group: Hodgkin Lymphoma Median Age At Death 65 Median Age At Death 65

7 Symptoms Painless swelling of lymph nodes Fever Night Sweats Weight Loss Itching Loss Appetite

8 Testing History /Physical LDH PET BM (not so much now) Biopsy

9 Hodgkin Lymphoma (HL) >95% of HL is CD30-positive 1 CD68 and CD163 may have prognostic significance Lymphoid neoplasm defined by the presence of Reed- Sternberg (RS) cells in a reactive infiltrate 2,3 9 Reproduced with permission from Mani H et al, References: 1. Diehl V et al. In: DeVita VT Jr et al, eds. Cancer: Principles and Practice of Oncology. Vol 2. 8th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2008: Pileri SA et al. J Clin Pathol. 2002;55(3): Stein H et al. In: Swerdlow SH et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008: American Cancer Society. Cancer Facts & Figures Atlanta, GA: American Cancer Society; Mani H et al. Clin Lymphoma Myeloma. 2009;9(3):

10 Early Stage Hodgkin’s Favorable –Clinical Stage I-II without risk factors Unfavorable –Risk Factors present B Symptoms Elevated ESR > 50 Mediastinal Mass > 3 Nodal Sites

11 Approximate Cumulative Risk of Recurrent Hodgkin's Lymphoma, Second Malignant Conditions, and Cardiovascular Events among Patients Receiving Both Radiotherapy and Chemotherapy for Early-Stage Hodgkin's Lymphoma Armitage JO. N Engl J Med 2010;363:

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13 Kaplan–Meier Estimates of Overall Survival and Freedom from Disease Progression. Meyer RM et al. N Engl J Med 2012;366:

14 Kaplan–Meier Estimates of Overall Survival and Freedom from Disease Progression among Patients with an Unfavorable Risk Profile. Meyer RM et al. N Engl J Med 2012;366:

15 12-Year Outcomes in Study Patients, According to Treatment Strategy. Meyer RM et al. N Engl J Med 2012;366:

16 Causes of Death, According to Treatment Strategy and Risk Profile. Meyer RM et al. N Engl J Med 2012;366:

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18 Early Stage Hodgkin’s Treatment continues to improve New Options are evolving and several options currently available Use of early response to PET may help Chemo ( ABVD or Stanford V) with XRT (involved site) ABVD alone Balance Up front benefit with Long term toxicity

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23 Kaplan-Meier analysis of the probability of (A) freedom from treatment failure and (B) overall survival in each treatment arm. Engert A et al. JCO 2009;27: ©2009 by American Society of Clinical Oncology

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25 Original Article ABVD versus BEACOPP for Hodgkin's Lymphoma When High-Dose Salvage Is Planned Simonetta Viviani, M.D., Pier Luigi Zinzani, M.D., Alessandro Rambaldi, M.D., Ercole Brusamolino, M.D., Alessandro Levis, M.D., Valeria Bonfante, M.D., Umberto Vitolo, M.D., Alessandro Pulsoni, M.D., Anna Marina Liberati, M.D., Giorgina Specchia, M.D., Pinuccia Valagussa, B.S., Andrea Rossi, M.D., Francesco Zaja, M.D., Enrico M. Pogliani, M.D., Patrizia Pregno, M.D., Manuel Gotti, M.D., Andrea Gallamini, M.D., Delia Rota Scalabrini, M.D., Gianni Bonadonna, M.D., Alessandro M. Gianni, M.D., for the Michelangelo Foundation, the Gruppo Italiano di Terapie Innovative nei Linfomi, and the Intergruppo Italiano Linfomi N Engl J Med Volume 365(3): July 21, 2011

26 Study Overview BEACOPP combination chemotherapy was compared with ABVD chemotherapy in advanced Hodgkin's disease. BEACOPP therapy was associated with higher initial rates of complete response and freedom from relapse but also with more short-term and long-term toxic effects.

27 Randomization, Treatment, and Follow-up. Viviani S et al. N Engl J Med 2011;365:

28 Kaplan–Meier Curves for Freedom from First Progression and Event-free Survival. Viviani S et al. N Engl J Med 2011;365:

29 Kaplan–Meier Curves for Freedom from Second Progression and Overall Survival. Viviani S et al. N Engl J Med 2011;365:

30 Outcomes and Important Adverse Events Associated with Initial Treatment, According to Regimen. Viviani S et al. N Engl J Med 2011;365:

31 Salvage Therapy and Outcome of Overall Intended Treatment. Viviani S et al. N Engl J Med 2011;365:

32 Conclusions Treatment with BEACOPP, as compared with ABVD, resulted in better initial tumor control, but the long-term clinical outcome did not differ significantly between the two regimens.

33 Advanced Stage Hodgkin’s Chemotherapy treatment of Choice Choice depends on where you are BEACOPP (Germany) ABVD/ Stanford V (USA) Use of early response to PET may help Balance Up front benefit with Long term toxicity Look at totality of care

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36 Cytotoxic agent The synthetic microtubule-disrupting agent, monomethyl auristatin E (MMAE, vedotin), that induces target cell death ADCETRIS is a CD30-Directed Antibody-Drug Conjugate ADCETRIS consists of three components: Linker A synthetic protease- cleavable linker that covalently attaches MMAE to the CD30-directed antibody and releases the agent within the target cell Antibody The antibody, brentuximab, specific for CD30 Reference: ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics Inc; 2012.

37 Nonclinical Data Suggest a Multistep Process for ADCETRIS Reference: ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics Inc; 2012.

38 Efficacy Results (relapsed HL after ASCT) Duration of response was calculated from the date of first response to the date of progression.

39 Summary Rare Cancer Highly Curable Staging Critical to understanding Treatment options Early Disease less may be more Advanced Disease PET may prove helpful Salvage with Transplant New Therapy including Brentuximab may change Options

40 Original Article Reduced Treatment Intensity in Patients with Early-Stage Hodgkin's Lymphoma Andreas Engert, M.D., Annette Plütschow, Ph.D., Hans Theodor Eich, M.D., Andreas Lohri, M.D., Bernd Dörken, M.D., Peter Borchmann, M.D., Bernhard Berger, M.D., Richard Greil, M.D., Kay C. Willborn, M.D., Martin Wilhelm, M.D., Jürgen Debus, M.D., Michael J. Eble, M.D., Martin Sökler, M.D., Antony Ho, M.D., Andreas Rank, M.D., Arnold Ganser, M.D., Lorenz Trümper, M.D., Carsten Bokemeyer, M.D., Hartmut Kirchner, M.D., Jörg Schubert, M.D., Zdenek Král, M.D., Michael Fuchs, M.D., Hans- Konrad Müller-Hermelink, M.D., Rolf-Peter Müller, M.D., and Volker Diehl, M.D. N Engl J Med Volume 363(7): August 12, 2010

41 Study Overview Investigators examined whether the intensity of treatment can be reduced in patients with early-stage Hodgkin's lymphoma without compromising antitumor efficacy. In a comparison of two with four cycles of ABVD chemotherapy plus either 20 or 30 Gy of involved-field radiation therapy, no significant differences were noted in disease-free or overall survival between the most and the least intensive regimens.

42 Numbers of Patients Randomly Assigned to Treatment Groups and Included in Analyses Engert A et al. N Engl J Med 2010;363:

43 Freedom from Treatment Failure and Overall Survival Engert A et al. N Engl J Med 2010;363:

44 Baseline Characteristics of the Patients According to Treatment Group Engert A et al. N Engl J Med 2010;363:

45 Adverse Events According to Treatment Group Engert A et al. N Engl J Med 2010;363:

46 Efficacy Outcomes According to Treatment Group Engert A et al. N Engl J Med 2010;363:

47 Conclusions In patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term effects of these treatments have not yet been fully assessed.

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55 5 – Year Relative Survival

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58 (A) Freedom from progression and (B) overall survival according to International Prognostic Score (IPS) factors (n = 740). Moccia A A et al. JCO 2012;30: ©2012 by American Society of Clinical Oncology

59 (A) Freedom from progression and (B) overall survival according to International Prognostic Score (IPS) factors for patients age ≤ 65 years (n = 686). Moccia A A et al. JCO 2012;30: ©2012 by American Society of Clinical Oncology

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63 Original Article ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin's Lymphoma Ralph M. Meyer, M.D., Mary K. Gospodarowicz, M.D., Joseph M. Connors, M.D., Robert G. Pearcey, M.D., Woodrow A. Wells, M.D., Jane N. Winter, M.D., Sandra J. Horning, M.D., A. Rashid Dar, M.D., Chaim Shustik, M.D., Douglas A. Stewart, M.D., Michael Crump, M.D., Marina S. Djurfeldt, M.Sc., Bingshu E. Chen, Ph.D., Lois E. Shepherd, M.D., for the NCIC Clinical Trials Group and the Eastern Cooperative Oncology Group N Engl J Med Volume 366(5): February 2, 2012

64 Study Overview In patients with limited-stage Hodgkin's disease, ABVD chemotherapy alone resulted in a higher rate of long-term (12-year) survival than either radiation therapy alone or radiation therapy plus ABVD chemotherapy, with significantly fewer late treatment-related deaths.

65 Second Cancers and Cardiac Events, According to Treatment Strategy. Meyer RM et al. N Engl J Med 2012;366:

66 Conclusions Among patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes.

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