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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

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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

Induction chemotherapy

CR No CR

Consolidation chemo Palliative care

Allo-transplant

Relapse?

Our general treatment paradigm for “fit” pts with AML Intent to cure

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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…

FR Appelbaum et al. Blood 2006

Intermediate risk Favorable risk What else?

• Drug resistance phenotypes
• Underlying sick BM/MDS
• Other genetic factors
• Host factors

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Decisions, decisions…

• Is the patient a candidate for induction

chemotherapy?

• Is the patient a candidate for allogeneic

transplantation?

A

60 patients with AML age 65-85 Normal organ function Daunorubicin 30 mg/m2/d IV day 1-3 Vincristine 1 mg/m2 IV day 2 Ara-C 100 mg/m2/d CIV day 1-7 When WBC>50K, PLT<15K, pain Hydrea 3 gm po day 1 and 4 Ara-C 100 mg/m2 s.c. bid day 2-3, 5-6

B

Lowenberg et al. JCO 7, 1268, 1989.

Induction vs Palliative Therapy for Older AML Patients

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Lowenberg et al. JCO 7, 1268, 1989.

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

Intensive Induction Versus Palliative Therapy for Older AML Patients

Induction chemotherapy in patients >60 yrs

Study Group Regimen Patients CR (%) Early death (%)

(within 30 days)

AMLCG TAD9 induction and consolidation +/- maintenance 511 51 27-34 BMRC DAT induction and consolidation 636 46-48 30-52 CALGB Standard or intensified 7+3 +/- maintenance 556 41-47 31-54 SECSG Idarubicin vs Daunorubicin + Cytarabine 111 53 20 EORTC-LCG- HOVON Mitoxantrone vs. Daunorubicin +/- LDAC3 maintenance 489 38-47 6-15 MDAC Cytarabine-based intensive induction 430 45 36 Clofarabine Clofarabine monotherapy 112 38 10 Emory Modified HiDAC induction/consolidation 59 69 10

M Arellano et al. Cancer 2011

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Older pts do not appear to benefit from dose intensification of AraC

All Patients

60 Years or Younger

Older Than 60

Mayer et al. NEJM 1994

Unrelated donor transplants by recipient age

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“MINI‐TRANSPLANTS”

Non‐myeloablative or Reduced Intensity conditioning

Cancer

Pre‐transplant Chemotherapy +/‐ Radiation

Donor Immune (T‐cell) Response

GOALS

• Reduce transplant‐

related risks

• Allow safer

transplantation of older pts and those with comorbidities or prior autologous BMT

CIBMTR analysis of RIC for AML/MDS

B.L. McCune et al. JCO 2010

Age is not a significant factor in outcomes DFS OS

AML‐CR1 MDS

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Carefully selected pts over the age of 70 can be successfully transplanted

AM Brunner et al. BBMT 2013

• 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)

AML Transplants at Emory in patients ≥ age 60 yrs

Age 60-64 yrs Age ≥65 yrs Years

Overall Survival

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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?

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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)

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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

Physical performance Cognitive function HD Klepin et al. Blood 2013

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Geriatric Assessment (GA) as a tool for predicting

• utcomes 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

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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

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