Characteristics and treatment of DLBCL in elderly patients

Transcription

1 Characteristics and treatment of DLBCL in elderly patients Lysa Experience or From Stephan to Ruth Eli 5/02/16 F.Peyrade Nice France

2 Age at Diagnosis

3 E(x) 10,00 9,00 8,00 7,00 6,00 5,00 4,00 3,00 2,00 1,00 0, E(x) * Kumar SK et al. Leukemia 2014;28(5): Source INED 2008

4 DLBCL Characteristics at diagnosis 98-5 (n=202 R-CHOP arm) 03-7B (n=150 R- minichop) 09-7B (n=120 pp OFA-mini CHOP) Trial / Age Phase III/ y PhaseII / >80y Phase II / 80y PS 0-1 % Ann Arbor I-II % aaipi 0-1 % LDH > N % Clinical DLBCL characteristics are not age dependant ORR in DLBCL is not age dependant

5 Epidemiological Heterogeneity Age and PS are not enough* Life expectancy at 70 years is heterogenous % 30% 20% Série1 * Repetto et al, JC0 2002

6 Pharmacological Heterogeneity Pharmacokinetic Absorption Distribution proteins Metabolisation Liver perfusion, Cytochrome P450 Elimination Renal insuffisiency compliance and polymedication Specific toxicity *Peyrade F et al. Lancet Oncol Aug;13(8):e344-52

7 Treatment R-miniCHOP Dose D1 D2 D3 D4 D5 Prednisone 40 mg/m² X X X X X Rituximab 375 mg/m² X Doxorubicin 25 mg/m² X Cyclophosphamide 400 mg/m² X Vincristine 1 mg DT X R-miniCHOP R-miniCHOP Inclusion 3 w 3w 3 w 3 w 3 w 4 w 3 months C1 C2 C3 C4 C5 C6 FU0 FU1 FUn RESPONSE RESPONSE Primary endpoint: overall survival

8 150 patients were included from january 2006 to january 2009 Median Age 84 (min 80-max 95) 1 withdrawal 149 patients treated Treatment Period 108 patients received 6 cycles of R mini CHOP 41 early withdrawal Progression = 10 Toxicities = 10 Voluntary withdrawal = 2 Other reasons = 1 Death = 18 Median follow-up: 20 months

9 Primary endpoint: Overall survival Intent-to-treat population Median: 29 months At two years: 59%

10 Primary endpoint: Overall survival Intent-to-treat population Median follow-up 41 months

11 Causes of death Toxicity Lymphoma progression Others Total Treatment Period 12 (including 5 during the first cycle) bleeding 2 chest pain 1 poor general condition 1 pneumopathy 27 2 unknow causes 1 stroke Follow-up Period acute renal insufficiency 1 poor general condition 31 3 unknown Total

12 Multivariate Analysis / Overall Survival Albumine level >35 g/l <=35 g/l P = Albumine isthe single statisticallysignificantprognosticfactor in a multivariate analysis

13 * Housemade protocol : adriamycin 35 mg/m² Lysa s scientific comity: doxorubicin cardiac toxicity *Italiano et al.haematologica. 2005; 90(9) 1281 Lysa s protocol: doxrubicin 25 mg/m²

14 7B trials: 150mg/m²??????? Aapro et al. Annals of Oncology 22: , 2011

15 Median age for DLBC L included in Lysa s phase II A cohort study involving more than 9,000 patients showed that at 8 years the probability of not suffering from cardiomyopathy was 79% for nonexposed patients and 74% for exposed patients Hershman et al J Clin Oncol. 2008;26(19):

16 Very few elderly patient in phase I studies Chau et al BMC Cancer 2011, 11:426 Italiano et al Annals of Oncology 19: , 2008

17 PHASE I Richardson PG et al: ImmunomodulatorydrugCC-5013 Blood 100: , 2002: medianage65 ans ZangariM et al: Resultsof phase I study of CC Blood 98:775a, 2001 (abstr3226): medianage 62 ans

18 09-7B Study PRE-PHASE PHASE INDUCTION PHASE CONSOLIDATION 9 semaines 10 semaines Oncovin Prednisone O-miniCHOP O-miniCHOP I 1 s 3 s 3 s 3 s 3 s 4 s 3 mois C1 C2 C 3 C4 C5 C6 FU0 FU1 FUn Evaluation Clinique REPONSE REPONSE PS 3,4 PS 1,2 PR<50%, PD CR, Cru, PR 50% Sortie Sortie LNH 09-7B OmCHOP

19 120 patients (from june 2010 à to jan 2011) median age 84 years (min 79 max 95) PS 0-2: 108 PS 3-4: 12 1 PS = 3 1 decision 1 major violation (death) Pre-Phase = steroid induced maniac acces 1 PS= 3 (death lymph progression) patients / cycles N Series1 5 treatment failure 3 toxicity 5 death 2 voluntary withdrawal 1 major violation 10 others nombre de cycle Median follow-up: 26.6 months 89 patients received prephase and 6 cycles

20 Primary endpoint: Overall survival FAS At 2 years: 64.7% [95% CI: %]

21 Causes of Death Toxicity Lymphoma progression Others Total 1 pulmonary oedema Treatment Period stroke 1 unknow causes 6 Follow-up Period infectious diseases 4 psychiatric syndroma 3 unknow 2 cardiac failure 1 tractor accident 39 Total

22 Toxicités Hématologiques Grade >= 3 Platelet toxicity Hemoglobin toxicity 5% 1,7% Febrile neutropenia toxicity Neutrophil toxicity 5,8 % 20,8% Infection 10,8%

23 ComprehensiveGeriatricEvaluation CGA is a Prognostic Factor CGA Therapeutic

24 Suivi Gériatrique 135 patients porteurs d un cancer Randomisation 70: traitement standard (TS) 65: traitement standard + suivi gériatrique (SG) SG: nombre d intervention 6.2±2.6 (range 0 15) Traitement conforme au protocole TS: 20% SG: 40% p 0;006 Toxicité Grade III/IV TS 53% SG:42% (P0.292). Kalsi T et al. British Journal of Cancer (2015) 112,

25 PROGNOSTIC FACTOR Albuminaemia OS attwoyears59% R-mini CHOP* Pré-Phase O-mini CHOP** aaipi OS attwoyears65% *Peyrade F et al. lancet Oncol.2011;12(5):460 8 **Peyrade F et al. ASCO 2014 OS >80 y similaros> 65 y

26 What we need Phase I dedicatedto olderpatient Phase II Very informative and fast if well designed

27 What we need Phase I dedicatedto olderpatient Phase II Very informative and fast if well designed Radiotherapy on PET-CT positive residual lymph nodes after CT Doxorubicin Dosage

28 Phase III: senior study: RminiCHOP +/- Lenalidomide CGA based clinical studies Jardin et al, clin trial.gov NCT

29 Phase IV studies Real life data among 100 patients treated for cancer Compliance50% Follow-up? Drug interaction Peyrade et al, personnal data

30 From Stephan Derrick.To DJ Ruth Flower