German Hodgkin Study Group

Transcription

1 German Hodgkin Study Group Deutsche Hodgkin Studiengruppe Avoiding Relapse of Hodgkin Lymphoma: Have We Moved The Needle? Andreas Engert, MD Chairman, German Hodgkin Study Group University Hospital of Cologne Cologne, Germany

2 Have We Moved the Needle in HL? Overview Background First line New approaches Summary HL, Hodgkin lymphoma

3 Hodgkin Lymphoma Cumulative relative survival (Sweden) Sjöberg J, et al. Blood. 2090;114: Abstract 1553.

4 Estimated Mortality Rates Hodgkin lymphoma Courtesy of Lena Specht 2012

5 Have We Moved the Needle in HL? Overview Background First line New approaches Summary

6 Freedom From Treatment Failure Freedom from Treatment Failure (FFTF) GHSG HD10 Study Weakest vs strongest arm (FFTF) HD10, arms A v s. D (ITT) At 5 years: 4 x ABVD + 30 Gy IFRT: 92.8% 2 x ABVD + 20Gy IFRT: 91.2% Difference -1,6%; 95% CI [-6,3%; 3,1%] A D Pts. at Risk Time [months] Time, Months A D ABVD, doxorubicin, 299 bleomycin, vinblastine, 252and dacarbazine; IFRT, involved-field radiotherapy Engert A, et al. N Engl J Med. 2010;363(7):

7 Question For a 55-year-old patient with stage II HL, all of the following are considered unfavorable risk factors except which of the following? 1. Elevated ESR (>50) 2. Presence of B symptoms 3. Elevated LDH (>2x ULN) 4. MMR >.35

8 Unfavorable Risk Factors for Stage I-II chl Risk Factor GHSG EORTC NCCN Age 50 Histology ESR and B symptoms >50 if A; >30 if B >50 if A; >30 if B >50 or any B symptoms Mediastinal mass MMR >.33 MMR >.35 MMR >.33 # Nodal sites >2 >3 >3 E lesion any Bulky >10 cm EORTC, European Organisation for the Research and Treatment for Cancer; ESR, erythrocyte sedimentation rate; GHSG, German Hodgkin Study Group; MMR, mediastinal mass ratio; MTR, mediastinal thoracic ratio; NCCN, National Comprehensive Cancer Network National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Renal cell carcinoma. V Available online at: f_guidelines.asp. Accessed October 18, 2016.

9 Early-Stage Hodgkin Lymphoma Current approaches Further reduction of chemo in early favorable failed (HD13) 1 PET-driven approaches in PET-negative failed (RAPID, H10) 2,3 PET-driven approaches in PET-positive were successful, new SOC? (H10) 3 Can new drugs such as BV and/or immune checkpoint inhibitors replace chemo/radiotherapy? BV, brentuximab vedotin; PET, positron-emission tomography; SOC, standard of care 1. Behringer K, et al. Lancet. 2015;385(9976): Radford J, et al. N Engl J Med. 2015;372(17): Raemaekers JM, et al. Haematol Oncol. 2015;33(S1): Abstract

10 Long-Term Results of HL Patients in advanced stages FFTF OS Years After Study Entry Canellos GP, et al. N Engl J Med. 2002;346(18):

11 Prognostic Factors for Advanced Hodgkin Lymphoma International Prognostic Score (IPS) Albumin <4 g/dl Hemaglobin <10.5 g/dl Male Age 45 years Stage IV disease Leukocytosis (white blood cell count at least 15,000/mm 3 ) Lymphocytopenia (lymphocyte count less than 8% of white blood cell count, and/or lymphocyte count less than 600/mm 3 Number of factors 5 years freedom from progression (%) Hasenclever D, et al. N Engl J Med. 1998;339(21): years overall survival (%)

12 Freedom From Treatment Failure HD15 in Advanced HL Freedom from treatment failure P value 60 months difference A vs B: % 97.5%-CI: [ 0.5%, 9.3%] A vs C:.5 1.1% 97.5% CI: [-3.7%, 5.8%] C vs B:.04 (ns) 3.9% 97.5% CI: [-0.5%, 8.2%] 5-yr freedom from treatment failure: A: 84.4% B: 89.3% C: 85.4% Time [months] A, 8 cycles of BEACOPP escalated B, 6 cycles of BEACOPP escalated C, 8 cycles of BEACOPP 14 Engert A, et al, Lancet. 2012;379(9828):

13 Have We Moved the Needle in HL? Overview Background First line New approaches Summary

14 Brentuximab Vedotin (SGN-35) Mechanism of action Brentuximab vedotin (SGN-35) ADC monomethyl auristatin E (MMAE), potent antitubulin agent protease-cleavable linker anti-cd30 monoclonal antibody ADC binds to CD30 ADC-CD30 complex traffics to lysosome MMAE is released MMAE disrupts Microtubule network G2/M cell cycle arrest Apoptosis

15 AETHERA: Study Design Cross over design, patients with POD on placebo could receive BV free of charge on a companion study Moskowitz CH, et al. Lancet. 2015;385(9980):

16 ECHELON-1: Phase III Trial BV + AVD vs ABVD in front-line advanced chl R A N D O M I Z E Brentuximab Vedotin 1.2 mg/kg q2w + AVD 28-day cycles ABVD 28-day cycles * Assessment based on Revised Response Criteria for Malignant Lymphoma E V A L U A T I O N Younes A, et al, J Clin Oncol. 2013;31(suppl): Abstract #TPS8612. National Institutes of Health. Available at: Accessed: September 21, 2016.

17 HD21: GHSG Perspective BV in advanced-stage HL 2 x BEACOPP esc 2 x BrECADD Centrally reviewed PET 4x BEACOPP esc 4x BrECADD End of therapy and residual nodes >2.5 cm: PET positive: Rx PET negative: Follow up GHSG, German Hodgkin Study Group; BEACOPPesc, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone; BrECADD, brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone; PET, positron emission tomography; RX, radiotherapy National Institutes of Health. Available at: Accessed: September 21, 2016.

18 Treatment of HL in Pts >60 Yrs BV + dacarbazine or bendamustine Treatment-naïve patients Age 60 years ECOG 3 Ineligible for conventional treatment BV alone BV + dacarbazine BV + bendamustine Patients with clinical benefit received additional cycles of BV Response assessed after cycles 2, 4, 8, 12, 16 Primary endpoint ORR N = 70 Yasenchak et al. Blood. 2015;126: Abstract 587.

19 Have We Moved the Needle in HL? Overview Background First line New approaches Summary

20 Have We Moved the Needle in Front-Line HL? Summary Hodgkin lymphoma has become one of the most curable cancers Combined modality therapy in early stages; ABVD and BEACOPP escalated in advanced stages High-dose chemotherapy (HDCT) and ASCT in R/R chl BV effective in RR chl; currently studied in combination Future trials will challenge chemotherapy and radiotherapy with less-toxic drugs ASCT, autologous stem cell transplantation; chl, classical Hodgkin lymphoma; R/R, relapsed/refractory