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:
Hodgkin’s Disease an Update. Is more always better? Jeffrey Schriber, M.D. Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center
Statistics at a Glance Percent Surviving 5 Years 85.3% 2004-2010 Percent Surviving 5 Years 85.3% 2004-2010
New Cases, Deaths and 5-Year Relative Survival Year19751980198519901994199820022006 5-Year Relative Survival 69.9%73.4%78.7%81.0%83.0%84.9%85.1%88.3%
Percent of New Cases by Age Group: Hodgkin Lymphoma Median Age At Diagnosis 39 Median Age At Diagnosis 39
Percent of Deaths by Age Group: Hodgkin Lymphoma Median Age At Death 65 Median Age At Death 65
Symptoms Painless swelling of lymph nodes Fever Night Sweats Weight Loss Itching Loss Appetite
Testing History /Physical LDH PET BM (not so much now) Biopsy
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, 2009 5 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; 2008:2167-2220. 2. Pileri SA et al. J Clin Pathol. 2002;55(3):162-176. 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; 2008:326-329. 4. American Cancer Society. Cancer Facts & Figures 2011. Atlanta, GA: American Cancer Society; 2011. 5. Mani H et al. Clin Lymphoma Myeloma. 2009;9(3):206-216.
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
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;363:653-662
Kaplan–Meier Estimates of Overall Survival and Freedom from Disease Progression. Meyer RM et al. N Engl J Med 2012;366:399-408
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;366:399-408
12-Year Outcomes in Study Patients, According to Treatment Strategy. Meyer RM et al. N Engl J Med 2012;366:399-408
Causes of Death, According to Treatment Strategy and Risk Profile. Meyer RM et al. N Engl J Med 2012;366:399-408
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
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):203-212 July 21, 2011
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.
Randomization, Treatment, and Follow-up. Viviani S et al. N Engl J Med 2011;365:203-212
Kaplan–Meier Curves for Freedom from First Progression and Event-free Survival. Viviani S et al. N Engl J Med 2011;365:203-212
Kaplan–Meier Curves for Freedom from Second Progression and Overall Survival. Viviani S et al. N Engl J Med 2011;365:203-212
Outcomes and Important Adverse Events Associated with Initial Treatment, According to Regimen. Viviani S et al. N Engl J Med 2011;365:203-212
Salvage Therapy and Outcome of Overall Intended Treatment. Viviani S et al. N Engl J Med 2011;365:203-212
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.
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
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.
Nonclinical Data Suggest a Multistep Process for ADCETRIS Reference: ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics Inc; 2012.
Efficacy Results (relapsed HL after ASCT) Duration of response was calculated from the date of first response to the date of progression.
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
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):640-652 August 12, 2010
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.
Numbers of Patients Randomly Assigned to Treatment Groups and Included in Analyses Engert A et al. N Engl J Med 2010;363:640-652
Freedom from Treatment Failure and Overall Survival Engert A et al. N Engl J Med 2010;363:640-652
Baseline Characteristics of the Patients According to Treatment Group Engert A et al. N Engl J Med 2010;363:640-652
Adverse Events According to Treatment Group Engert A et al. N Engl J Med 2010;363:640-652
Efficacy Outcomes According to Treatment Group Engert A et al. N Engl J Med 2010;363:640-652
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.
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):399-408 February 2, 2012
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.
Second Cancers and Cardiac Events, According to Treatment Strategy. Meyer RM et al. N Engl J Med 2012;366:399-408
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.