Elderly Patients with Hodgkin s Lymphoma: FIL experience. Massimo Federico University of Modena and Reggio Emilia

Transcription

1 Elderly Patients with Hodgkin s Lymphoma: FIL experience Massimo Federico University of Modena and Reggio Emilia

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3 RESULTS OF VbMp CHEMOTHERAPY REGIMEN IN ELDERLY PATIENTS WITH HODGKIN DISEASE: THE GISL EXPERIENCE ( ) VbMp Every days for6 cycles + IF-RT 36 Gy 4 weeks Drug Dose Cycles Vinblastine 6 mg/m (on day1 and 8) Bleomycin 10 mg/m (on day1 and 8) 4 mg/m (on day1 and 8) Methotrexate 30 mg/m (on day1 and 8) Prednisone 25 mg/m (on days1-5 and 8-12) Polimeno G, et al. Hematologica 2005

4 Median Age 72 (65-83) Stage I II III IV B symptoms Absent Present Histology Nodular Sclerosis Mixed Cellularity Lymphocyte predominant Baseline Characteristics N % % 37% 5% 11% 79% 21% 53% 32% 15%

5 Treatment Response Response N= 19 % Stage I-II Stage III-IV CR 14 74% 1 (33%) 15 (95%) PR 2 11% - SD 2 11% - 2 (67%) PD 1 14% 1 (5%) - 5-yr OS = 72.7%

6 Levis et al., Annals of Oncology 2004

7 VEPEMBSchedule (every 28 days) Vinblastin 6 mg/m2 i.v. Day 1 Cyclophosphamide 500 mg/m2 i.v. Day 1 Procarbazine 100 mg/m2 p.o. Days 1-5 Prednisone 30 mg/m2 p.o. Days 1-5 Etoposide 60 mg/m2 p.o. Days Mitoxantrone 6 mg/m2 i.v. Day 15 Bleomycin 10 mg/m2 i.v. Day 15 Levis et al., Annals of Oncology 2004

8 Levis et al., Annals of Oncology 2004

9 Levis et al., Annals of Oncology 2004

10 Levis et al., Annals of Oncology 2004

11 Levis et al., Annals of Oncology 2004

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13 > 65 yrs VEPEMB ABVD RT

14 ORIGINAL END-POINT

15 UPDATED END-POINT

16 Treatment Study Plan

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21 MVBD in elderly patients and/or with heart disease (HD0803) Myocet Bleomycin Vinblastine Dacarbazine 25 mg/mq (in 60 minutes) 10 mg/mq 6 mg/mq 375 mg/mq Cycles repeated every 28 days Days 1 and 15 Days 1 and 15 Days 1 and 15 Days 1 and 15 Alessandro Levis, Alessandro Pulsoni, Sergio Storti, Michele Spina

22 MBVD (HD-0803) 70 years or cardiopatic younger pts Staging with TC-PET Geriatric assessment Stage I-IIA Supported by G-CSF and EPO according to national guidelines Stage IIB-IV 2 MBVD 2 MBVD PET-2 1 MBVD PET-6 4 MBVD Involved field RT 30 Gy or 36 Gy if PET+ Final PET +/- RT 30Gy limited to bulky or PET+ area

23 FIL HD patients Male Female Age Median Age ElderlyAge 70 Young cardiopathicpatients aged <70 years (range 46-84) 41 6 Localized stage I-IIA Advanced stage IIB-IV 13 (28%) 34 (72%)

24 HD0803 Response Analysis CR evaluated after 6 cycles or before in patients who discontinued treatment RC PET 2 Fine terapia RC RP SD/PD NV Localized stages (13 pts) Stages IIB-IV (34 pts) CR=77%

25 FIL HD0803 Treatment: Cycles administered % Causes of discontinuation of therapy (13 patients) - Withdrawal of consent / poor compliance (2) - Progression (1) - Toxicity (9) -> 3 toxic deaths - synchronous neoplasia of the lung (1) cicli 5 cicli 4 cicli 3cicli 2 cicli 1 ciclo Stages I-IIA: 13/13 patients completed 3 cycles of chemotherapy Stage IIB-IV: 21/34 (62%) patients performed 6 chemotherapy cycles

26 FIL HD0803 G 3-4 Acute Toxicity % LVEF 15% in none 20 of the patients Haematological toxicity Infections cardiac toxicity

27 Progression free survival Stages I-IIA Stages IIB-IV 34%

28 PFS in high risk patients stratified by comorbidity No comorbidity G >1 Comorbidity G2-3 (19 pts)

29 FIL HD0803 Overall Survival

30 FIL HD0803 Deaths Deceased patients after a median follow-up of 28 months: 10/47 Stage I-IIA: 0/13 Stage IIB-IV: 10/34 Death reasons n. of patients Lymphoma 3 Acute toxicity (TRM) 3 (1 IMA; 1 bronchopneumonia, 1 sepsis ) Late events ( > 1 year) Other 2 (1 heart failure; 1 pneumonia, thrombocytopenia and digestive hemorrhage) 2 lung cancer (diagnosed within 7 months after the end of therapy) Toxic deaths (TRM): 3/47 = 6 % Acute and late cardiac toxicity: 2/47=4%

31 Clinical trials with ABVD or ABVD-like in elderly patients Median Age CR (%) Toxic death (%) ABVD Shield study, Proctor 2011 MBVD Studio FIL COPP/ABVD *** GHSG HD9 Study, Ballova 2005 ABVD *** Evens, 2013 ABVD Boll, % 14% 75 77% 6% 70 77% 8% 66 65% 9% 65 89% 5% ***Advanced stages Localized stages

32 FIL BV HD01 A phase II study of Brentuximab Vedotin (BV) in the treatment of elderly Hodgkin lymphoma (HL) patients at first relapse or with primary refractory disease

33 Inclusion Criteria Histologically confirmed CD30-positive disease Elderly patients at first relapse or with primary refractory HL (i.e. patients who have previously received only 1 line of treatment. ) Age greater than or equal to 60 years. Exclusion Criteria Previous treatment with BV Peripheral neuropathy > grade 1. Known history of any of the following cardiovascular conditions: -Myocardial infarction within 2 years of study entry. -Congestive heart failure, Class III or IV, by the NYHA criteria. -Evidence of current uncontrolled cardiac arrhythmias, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Known cerebral/meningeal disease.

34 Treatment BV will be administered as a single IV infusion on Day 1 of each 21-day cycle for 16 cycles BV 1.8 mg/kg, administered via outpatient IV infusion on Day 1 of each 21-day cycle. Planned accrual 20 patients

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