MANAGEMENT OF OLDER PATIENTS WITH AML Finding the “fit” Amelia Langston, MD Professor of Hematology ‐ Oncology Emory University School of Medicine Disclosure I have nothing relevant to this presentation to disclose 1
What am I going to say? • Treatment of older people with AML is not a one ‐ size ‐ fits all proposition • AML in older people is intrinsically less curable (with chemotherapy) than AML in younger adults – Aggressive therapy can’t just be a “bridge to nowhere…” – “Fit” older people with AML should be approached using the same basic paradigm we use for everyone else— including consideration of allogeneic transplantation Our general treatment paradigm for “fit” pts with AML Intent to cure Induction chemotherapy CR No CR Consolidation Allo-transplant Palliative chemo care Relapse? 2
Older people are more likely to have less favorable cytogenetic profiles FR Appelbaum et al. Blood 2006 …but there’s more going on than bad chromosomes… Intermediate risk Favorable risk What else? •Drug resistance phenotypes •Underlying sick BM/MDS •Other genetic factors •Host factors FR Appelbaum et al. Blood 2006 3
Decisions, decisions… • Is the patient a candidate for induction chemotherapy? • Is the patient a candidate for allogeneic transplantation? Induction vs Palliative Therapy for Older AML Patients Daunorubicin 30 mg/m 2 /d IV day 1-3 A Vincristine 1 mg/m 2 IV day 2 Ara-C 100 mg/m 2 /d CIV day 1-7 60 patients with AML age 65-85 Normal organ function When WBC>50K, PLT<15K, pain Hydrea 3 gm po day 1 and 4 Ara-C 100 mg/m 2 s.c. bid day 2-3, 5-6 B Lowenberg et al. JCO 7, 1268, 1989. 4
Intensive Induction Versus Palliative Therapy for Older AML Patients Induction Palliative care CR Rate 58% 0% Early death 3/31 18/29 Median survival 21 weeks 11 weeks Survival at 2.5 yr 13% 0% Days in hospital 55 50 Lowenberg et al. JCO 7, 1268, 1989. Induction chemotherapy in patients >60 yrs Study Group Regimen Patients CR (%) Early death (%) (within 30 days) TAD9 induction and consolidation +/- AMLCG 511 51 27-34 maintenance DAT induction and consolidation BMRC 636 46-48 30-52 Standard or intensified 7+3 +/- CALGB 556 41-47 31-54 maintenance Idarubicin vs Daunorubicin + SECSG 111 53 20 Cytarabine Mitoxantrone vs. Daunorubicin +/- EORTC-LCG- LDAC 3 maintenance 489 38-47 6-15 HOVON Cytarabine-based intensive induction MDAC 430 45 36 Clofarabine monotherapy Clofarabine 112 38 10 Modified HiDAC Emory 59 69 10 induction/consolidation M Arellano et al. Cancer 2011 5
Older pts do not appear to benefit from dose intensification of AraC 60 Years or Younger All Patients Older Than 60 Mayer et al. NEJM 1994 Unrelated donor transplants by recipient age 6
“MINI ‐ TRANSPLANTS” Non ‐ myeloablative or Reduced Intensity conditioning Pre ‐ transplant Donor Immune (T ‐ cell) Response Chemotherapy +/ ‐ Radiation GOALS • Reduce transplant ‐ related risks Cancer • Allow safer transplantation of older pts and those with comorbidities or prior autologous BMT CIBMTR analysis of RIC for AML/MDS Age is not a significant factor in outcomes AML ‐ CR1 MDS DFS OS B.L. McCune et al. JCO 2010 7
Carefully selected pts over the age of 70 can be successfully transplanted •Single center report—Dana Farber Cancer Inst. •N=54 pts -- age ≥ 70 yrs with heme malignancies receiving allo-HPCT •Median HCT CI score = 1 (range 0-5) AM Brunner et al. BBMT 2013 AML Transplants at Emory in patients ≥ age 60 yrs Overall Survival Age 60-64 yrs Age ≥ 65 yrs Years 8
Observations from early studies of reduced intensity allogeneic transplantation in AML • Reduced early mucositis, organ toxicity, duration of pancytopenia, early mortality • Shift toward later occurrence of GVHD • 1 yr NRM ~15 ‐ 30% • Disease relapse is a major issue for AML and MDS • Poor long term disease control in pts with active disease (>5% blasts) at time of transplant Who are these “fit” older people and how do we identify them? 9
What tools can we use? • Comorbidities ‐‐‐ HCT ‐ Comorbidity Index • Geriatric assessment tools – Functional status • ADL abilities • Simple performance tests—grip strength, 15 second walk, etc – Cognitive function – Mental health/depression Hematopoietic Cell Transplant Comorbidity Index (HCT ‐ CI) ML Sorror et al. Blood 106: 2912 (2005) 10
HCT ‐ CI score predicts NRM and Survival after ALLO ‐ SCT ML Sorror et al. Blood 106: 2912 (2005) Geriatric assessment tools predict survival of older pts (> age 60) with AML receiving induction chemotherapy Cognitive function Physical performance HD Klepin et al. Blood 2013 11
Geriatric Assessment (GA) as a tool for predicting outcomes after allo ‐ HPCT in older pts • Single center prospective study examining the predictive value of established measurement tools to assess pts ≥ age 50 prior to allo ‐ HPCT – Functional status – Frailty – Comorbidity – Nutritional status – Mental health – Inflammation • Primary endpoints of interest: 2 yr OS and NRM LS Muffly et al. Haematologica 2014 LS Muffly et al. Haematologica 2014 12
LS Muffly et al. Haematologica 2014 Conclusions • The biology of AML in the elderly is generally unfavorable • Chemotherapy alone is unlikely to be curative for most patients • A combination of functional assessments and comorbidity scoring can be used to select patients who may be candidates for aggressive therapy, including allo ‐ transplantation 13
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