39% Treated. 61% Untreated. 33% UnRx. 45% UnRx. 59% UnRx. 80% UnRx

Transcription

1 AML in the Elderly สน น ว ส ทธ ศ กด ช ย งานประช มว ชาการกลางป สมาคมโลห ตว ทยาแห งประเทศไทย คร งท ต ลาคม 2561 ณ โรงแรมเลอ เมอร เด ยน เช ยงใหม จ งหว ดเช ยงใหม

2 33% UnRx 45% UnRx 59% UnRx 80% UnRx Data from Surveillance, Epidemiology, and End Results program data from 2000 through 2007 linked to Medicare enrollment and utilization data in the United States. 61% Untreated 39% Treated Haematologica. 2012; 97(12):

3 AML: Overall Survival Age years Age 60 years Blood Review. 2017; 31:43-62.

4 Life Expectancy Life expentancy in 2016 World Bank Data; accessed on 15th Oct 2018 The human lifespan Probably unalterable biological limit. Limitation of~115 years Virtually all humans will die before age 90 years. Life expectancy in the US: >77 years 2013 / 2014 Not change 2015 / 2016 Decreased Published at annals.org on 25 September 2018.

5 AML Not treat Best supportive care Treat Low intensity therapy Hypomethylating agents Low dose ara-c Intensive chemotherapy Novel agent/therapy Age Performance Comorbid Disease Status (AML) 70 Good None Favorable 70 Good None Adverse 70 Good Multiple Favorable 70 Good Multiple Adverse 70 Poor None Favorable 70 Poor None Adverse 70 Poor Multiple Favorable 70 Poor Multiple Adverse

6 Treat?

7 Age years From trials AGE 60 years Blood Review. 2017; 31:43-62.

8 Median Survival = 2.4 months 33.8% received CMT Age (years) 1 Year OS 2 Years OS % 15.8% % 5% % 1.7% SEER Analysis Data from Surveillance, Epidemiology, and End Results program data from 2000 through 2007 linked to Medicare enrollment and utilization data in the United States. Age (years) 3 Years Survival 5 Years Survival % 3-8% < 60 Upto 50% Haematologica. 2012; 97(12):

9 The Swedish Acute Leukemia Registry: All management Blood. 2009; 113:

10 Data from Surveillance, Epidemiology, and End Results program data from 2000 through 2007 linked to Medicare enrollment and utilization data in the United States. 61% Untreated 39% Treated Haematologica. 2012; 97(12):

11 AML in the Elderly Assuming that therapy is mostly futile and palliation more appropriate: Only about 1/3 of older patients receive treatment for AML. Age remains an arbitrary variable and is increasingly understood to be a poor discriminator of outcome.

12 Median sur.(mo): Treated Untreated Age 65-69: 10 4 Age 70-74: 8 3 Age 75-79: 6 2 Age 80: 3 1 Haematologica. 2012; 97(12):

13 The Swedish Acute Leukemia Registry: All management Intensive treatment Blood. 2009; 113:

14 Treated: Better survival.

15 Treatment: Concerns Prolonged hospitalization Intensive supportive care Costly and cumbersome High early death rates/treatment related mortality Early death rates of 17% to 54% among elderly have been reported. Resistance to treatment Not in complete remission Not prolong survival duration

16 Objectives Prolong survival Complete remission Low TRM Low early death Quality of life Less hospitalisation (duration & frequency) Less expense Less intervention

17 Who?

18 AML (excluding APL) in the elderly Patient characteristics ECOG PS Comorbidities Age Disease characteristics Cytogenetic / molecular markers WBC at diagnosis Secondary vs de novo AML

19 Pretreatment scores Treatment mortality score AML score PINA Revised Charlson Comorbidity index (CCI) Haemotopoietic cell transplantation comorbidity index (HCT-CI) Comprehensive geriatric assessment

20 Haemotopoietic cell transplantation comorbidity index (HCT-CI) Leuk Res. 2012; 36(4):

21 Leuk Res. 2012; 36(4):

22 Age > 60: Age 60: ED = 41%; MOS 63 D ED = 28%; MOS 303 D HCT-CI Score 0 ED = 19%; MOS 306 D HCT-CI Score 1,2 ED = 36%; MOS 133 D HCT-CI Score 3 ED = 54%; MOS 34 D Leuk Res. 2012; 36(4):

23 ` Age > 60 years ECOG PS 2 High HCT-CI WBC > 1000x19 9 /L Leuk Res. 2012; 36(4):

24 Median sur.(mo) Treated Untreated CCI 0: 7 3 CCI 1: 6 2 CCI 2: 4 2 Haematologica. 2012; 97(12):

25 Median sur.(mo) Treated Untreated Previous MDS 5 2 No previous MDS 7 2 Haematologica. 2012; 97(12):

26 Early Deaths Haematologica. 2012; 97(12):

27 Blood. 2009; 113:

28 Accepted Scoring Systems Currently, there are no universally accepted prognostic and predictive scoring systems applicable to all older adults with AML Identify medically fit patients who are able to tolerate intensive treatment with minimal TRM

29 Better Survival / Lower Early Death Lower age Good performance status Less cormorbidity

30 OS:Favorable Risk Cytogenetics OS: Poor Risk Cytogenetics OS:Intermediate Risk Cytogenetics OS: Poor Risk Cytogenetics

31 Blood May 1; 107(9): SWOG Leukemia Committee

32 Favorable Genetics: Better Sur.

33 How?

34 How to Treat? Intensive chemotherapy (IC) Non intensive chemotherapy Low intensity treatment Low dose cytarabine (LDC) Hypomethylating agents (HMA) Best supportive care (BSC)

35 CR patients live longer. J Clin Oncol Apr 1; 28(10):

36 Complete Remission Patients in remission from acute leukemia require less supportive care and hospitalization and have a better quality of life than patients during palliation. Remission, even if short-lived, is therefore a reasonable aim also in elderly patients. Blood. 2009; 113: )

37 Blood. 2009; 113:

38 Induction Chemotherapy Regimen Author N / Age Outcomes (CR: 40-60%) Ara C 100 DNR 45 Yates et al / 53 (17-78) CR 65% - ED (10-20%) Ara C 100 DNR / ADM 30 Ara C 100 DNR 45/IDA 12/MA 12 Ara C 200 DNR Ara C 100 DNR Ara C 200 DNR 80/IDA 12 Yates et al / 48 (1-84) Age > 60: CR 31-47% - Rowe et al / 68 (56-86) CR 42% Age 70: CR 46-55% Age > 70: CR 24-33% 13-22% Lowenberg et al / 67 (60-83) CR 54-64% 11-12% Burnett et al / 53 (16-72) CR 73-75% 5-10% Pautas et al / 60 (50-70) CR 70-83% 3-8%

39 Low-Intensity Regimens Regimen Author N / Age Outcomes CR: 20-40% ED30 (10%) LDAC 20 mg x2x10 D Burnett et al / 74 (51-90) CR 18% 26% Clofarabine 20 mg/m2x 5 D Burnett et al / 74 (51-90) CR 22% 18% Clofarabine 30 mg/m2 x 5 D Kantarjian et al / 71 (60-88) CR 38% 10% Azacitidine 75 mg/m2 x 7 D Fenaux et al / 70 (50-83) CR 18% NA Azacitidine Dombret et al / 75 (64-91) CR 27.8% 6.6% Decitabine 20 mg/m2 x 5 D Cashen et al / 74 (61-87) CR 24% 7% Decitabine/LDAC/BSC Kantajian et al / 73 (64-91) CR 18% 9% Decitabine 20 mg/m2 x10d Blum et al / 74 (60-85) CR 47% 15% GO / BSC Amadori et al / 77 (62-88) CR 15.3% 11%

40 New / Experimental Therapies Hypomethylating agents Guadecitabine Histone deacetylase inhibitors Vorinostat Pracinostat Panobinostat Entinostat FLT3 inhibitors Quizartinib Sorafenib Midostaurin Crenolanib Gilteritinib ASP2215 Cytotoxic agents Sapacitabine Vosaroxin Cell cycle inhibitors Barasertib Volasertib Rigosertib Monoclonal antibodies SL-401 Anti-CD47 Ipillimumab Nivolumab Lintuzumab-Ac225 SGN-CD33A (Vadastuximab talirine) Other early phase agents ABT-199 (Venetoclax) AG-221 AG120 CPX-351 (Vyxeos)

41 Approach: AML in the elderly Fit / Unfit: Age, performance status, and comorbidities Choose treatment: Fit: Intensive chemotherapy Unfit: Low intensity treatment (HMA / LDAC) Achieve CR? Not CR: Clinical trial / BSC CR: Consolidation therapy Consolidation with? RIC allo-hct if adverse risk disease IDAC if low risk disease Adverse risk dis. without donor for allo-hct

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