OF LIFE AMONG OLDER ADULTS WITH HEMATOLOGIC MALIGNANCIES

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1 GERIATRIC ASSESSMENT AND QUALITY OF LIFE AMONG OLDER ADULTS WITH HEMATOLOGIC MALIGNANCIES Daneng Li, MD Assistant Clinical Professor Medical Oncology & Therapeutics Research Erin Kopp M.S.N, A.C.N.P-B.C., C, N.P Nurse Practioner Department of Hematology How the Experts Treat Hematologic Malignancies Las Vegas, NV March 17, 2017

2 Disclosures I do not have anything to disclose.

3 Objectives To understand the components of geriatric assessment in the care of older adults with cancer To understand potential applications for geriatric assessment tin hematologic malignancies i

4 Background Aging g US populationp Projected 88.5 million > 65yrs by 2050 More than double of 40.2 million in 2010 Cancer associated with aging By 2030, ~70% of all cancer diagnosis will occur in patients age > 65 Vincent GK et al. Smith BD et al. J Clin Oncol 2009

5 Background Older adults significantly underrepresented in clinical trials 11% of physicians reported age alone as reason for not enrolling older adults Low proportion of participation i in FDA registration ti trials and trials from National Clinical Trials Network Percentage enrolled onto cooperative group trials remained flat at ~20% between Hutchins et al. N Engl J Med 1999 Hurria et al. J Clin Oncol 2015 Javid SH et al. Oncologist 2012

6 For Older Adults:

7 Swedish Registry Data Juliusson et al. Clinical Lymphoma Myeloma and Leukemia 2011

8 AML Mortality Within 30 days of Initiating Induction Therapy Toxicity Increases with Age 35 32% % 30-D Day Mortality % 20% 5 3% 0 < >75 Age (Years) Applebaum et al. Blood 2006

9 Frequency of AML therapy use by age and CCI. SEER/Medicare Data N = Newly diagnosed AML Age >65 39% Received Therapy CCI= Charlson Comorbidity Index Betul Oran and Daniel J. Weisdorf Haematologica 2012

10 Survival Benefit with Treatment US Population Data (SEER/Medicare) Treated Untreated yrs 10 Months 4 Months yrs 8 Months 3 Months yrs 6 Months 2 Months 80+ yrs Benefit not seen Factors independently associated with overall survival in SEER data: Received R i d treatment t t Younger age Lower co morbidity Higher income Absence of prior MDS Adapted from Klepin, H ASCO 2013 Oren et al. Haematologica, 2012

11 How do we better select patients for intensive therapy? Author Tumor Characteristics Clinical Variables Patient Characteristics Krug 1 (N=1406) Secondary AML Body temp, Hgb, Age Molecular/Cytogenics platelets, LDH, fibrinogen Kantarjian 2 (N=446) Complex karyotype Creatine> 1.3 Age ECOG PS Wheatley 3 (N=2483) Cytogenetic risk group WBC count Age Secondary AML ECOG PS Rollig 4 (N=909) Karyotype, NPM1 WBC count, Age mutation status, CD34 LDH expression Outcomes Early death Early death Survival (1 year) Survival Predictive models weighted towards tumor biology Adapted from Klepin, H. ASCO 2013 Krug et al. Lancet 2010 Kantarjian et al. Blood 2010 Wheatley et al. British Journal of Haematology 2009 Rollig et al. Blood 2010

12 Aging is a Heterogeneous Process Same Chronological Age; Different Functional Same Chronological Age; Different Functional Age

13 Geriatric Assessment (GA): A Multidisciplinary Approach Functional status Cognition Comorbidity Nutrition Polypharmacy Psychosocial

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15 Cancer Specific GA Domains & Measures Domain Functional Status Cognition Comorbidity Psychological State Measure Activities of Daily Living (subscale of MOS Physical Health) Instrumental Activities of Daily Living (subscale of the OARS) Karnofsky Physician-Rated Performance status No. of falls in last 6 months Timed Up & Go Blessed Orientation-Memory-Concentration Test (BOMC) Physical Health Section (subscale of the OARS) MHI Depression and Anxiety Social Activity MOS Social Activity Survey Social Support Nutrition MOS Social Support Survey: Emotional/Information and Tangible Subscales Body Mass Index Percent unintentional weight loss in last 6 months

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26 Geriatric Assessment in Older Adults with Cancer Predict toxicity to cancer treatment Predict survival for older cancer patients Uncover problems not detected by routine H&P Improves mental health and well-being Improves pain control Feyer et al. Ann Oncol 2005 Maione et al. JCO 2005 Repetto et al. JCO 2002 Chen et al. Cancer 2003 Rao et al. J Gerontol A Biol Sci 2005 Extermann et al. CROH 2004

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30 GA methods can inform risk stratification Multi-site study Age >60 years Age MDS (N=63) or AML (n=132) MDS 66% 27% 16% GA Predictors: AML 34% 73% 84% KPS 70 (20 90) Funtion (ADL/IADL, TUG (range) (30 80) (40 90) -Cognition (MMSE) HCT CI Mood (GDS) -QOL (EORTC QLQ-C30) Q Independent predictors of OS for Outcome: OS non intensively treated patients Treatment: -Best supportive care % BM blasts 20 Impaired ADL (BSC) Cytogenetics Fatigue 50 -HA (hypomethylating KPS<80 agents) HCT CI 3 -Intensive chemotherapy BSC (N=47) HA (N=73) IC (N=75) Adapted from Klepin, H. ASCO 2013 Deschler et al. Haematologica 2013

31 Adapted from Klepin, H. ASCO 2013 Deschler et al. Haematologica 2013

32 Geriatric assessment predicts survival for older adults receiving induction chemotherapy for AML Klepin et al. Blood 2013

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34 3MS=Modified Mini-Mental State Exam CES-D= Center for Epidemiologic Studies Depression Scale DT=Distress Di Thermometer PAT-D=Pepper Assessment Tool for Disability (includes mobility, ADLs and IADLs SPPB=Short Physical Performance Battery

35 Standard clinical characteristics including those proposed by the Kantarjian predictive model for early mortality explained only 21% of the variability in OS. The addition of cognitive function and PF explained an additional 12% (a 60% relative increase in predictive power).

36 Summary Limited patient characteristics currently exist to guide treatment of hematologic malignancies such as AML GA can provide additional information to help to risk stratify patients t undergoing treatment t t for hematologic malignancies i Increased incorporation of GA into hematologic malignancy clinical trials can help to inform its use in routine practice

37 Erin Kopp M.S.N, A.C.N.P-B.C., N.P.

38 Disclosures No disclosures

39 Objectives Review common hematologic malignancies seen in the older adult Identify factors unique to the older adult that contribute to prognosis Discuss quality of life findings for older adults with hematologic malignancies Discuss methods to improve quality of life in the older adult with a hematologic malignancy

40 Hematologic malignancy Median age of diagnosis 30% of patients newly diagnosed with hematologic malignancy are over age 75 (hamaker) Lymphoma Non-Hodgkin lymphoma-83% of patients diagnosed after the age of 50 Leukemia CLL- age 71; AML- age 67; CML-age 64 Multiple Myeloma, MDS, Hodgkin Lymphoma, ALL

41 Factors contributing to prognosis in the older adult undergoing treatment for hematologic malignancy Type of hematologic malignancy/treatment Functional age Increased numbers of comorbidities Decreased organ reserve Polypharmacy Performance status prior to diagnosis and treatment Development of geriatric syndromes USE of GERIATRIC ASSESSMENT KEY

42 Treatment approaches and lifelong effects Surgery Radiation- skin damage, organ damage, loss of function Chemotherapy-cardiotoxicity, pulmonary toxicity, neuropathy, cognitive changes Immunotherapy-infection risk, PML, CRS, unknowns

43 Decreased organ reserve Pre-treatment- diagnostic testing, supportive medications, medications for cormorbidities, nutrititional status, fluid/electrolyte balance Treatment-side t effects, nutritional status, t medications to manage symptoms Post-treatment-immunosuppression, treatment anti-infectives, infectives, fluid/electrolyte balance Orthostatic hypotension, anticholinergics, opiates

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45 Polypharmacy Many ypatients are on multiple medications prior to cancer diagnosis Medications required to manage toxicity are often dangerous in the older adult Beers Criteria for potentially inappropriate drugs AGS website *

46 How to Use AGS 2015 Beers Criteria Key Principles to Guide Optimal Use of the American Geriatrics Society (AGS) 2015 Beers Criteria 1 Medications in the AGS 2015 Beers Criteria are potentially inappropriate, not definitely inappropriate. 2 Read the rationale and recommendations statements for each criterion. The caveats and guidance listed there are important. 3 Understand why medications are included in the AGS 2015 Beers Criteria i and adjust your approach hto those medications accordingly. 4 Optimal application of the AGS 2015 Beers Criteria involves identifying potentially inappropriate medications and where appropriate offering safer nonpharmacological and pharmacological therapies. 5 The AGS 2015 Beers Criteria should be a starting point for a comprehensive process of identifying and improving medication appropriateness and safety. 6 Access to medications included in the AGS 2015 Beers Criteria should not be excessively restricted by prior authorization and/or health plan coverage policies. 7 The AGS 2015 Beers Criteria are not equally applicable to all Patients- review current meds if concerned about interactions at Clinicians- use Beers criteria as a warning sign to do an in depth review of the medication and potential interactions Use criteria as a tool to decide on whether to adjust prescriptions with patient Make sure to taper medication when switching Assess for interactions/symptoms in individual patient Patients- review meds at g p g Clinicians-

47 Functional Status Beyond ECOG and KPS Activities Daily Living Bathing Dressing Toileting Transferring Continence Feeding Instrumental ADL Use telephone Shopping Food preparation Housekeeping Laundry Transportation (drives or takes public transport) Take own meds Handle finances

48 Functional Status and Quality of Life Inability to return to previous level of activity is associated with decreased quality of life (Pergolotti) Geriatric assessment can identify deficits overlooked otherwise Utilization of PT/OT Physical therapy improves gait and physical function OT focuses on participation in activities, cognitive function, IADL Study by Pergolotti et al showed that age, comorbidities and level of education increased odds of functional limitations that are modifiable

49 Geriatric Syndromes Older adults are prone to having geriatric syndromes Health related conditions that do not follow a specific diagnosis Are prevalent in older adults, especially the frail elderly Can impact patient quality of life and poor outcomes What are geriatric syndromes?...

50 Considerations in Geriatric Syndrome Multiple morbidities Polypharmacy Cognitive impairment Frailty Disabilty Sarcopenia Malnutrition

51 SPICES Framework for Assessment Systematic screening tool Signals need for more specific assessment Acronym of six common marker conditions S is for sleep disorders P is for problems with eating or feeding I is for incontinence C is for confusion E is for evidence of falls S is for skin breakdown Used with permission

52 Quality of life for patients with hematologic malignancies Quality of life associated with different factors by individual Multiple studies show the importance of baseline Quality of Life parameters as independent prognostic factors in this population (deschler) How to accurately predict effects of disease and selected treatment on future QOL Deeg & Steuten show that QOL in patients post transplant with AML have decreasing scores correlated with age

53 Decrease in QOL consistent among hematologic malignancy sufferers

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58 Recommendations Ask patient what factors contribute to individual perception p of good QOL Identify and intervene early for modifiable factors that may diminish i i QOL now and in the long term Utilize geriatric assessment approaches throughout the treatment continuum Assemble multidisciplinary team to address challenges from a multi-pronged approach Reevaluate QOL at multiple time points along care continuum

59 Case Study AR- 70y/o male with Lives with elderly wife that history of myelodysplastic suffers from early syndrome dementia Progression to AML Responsible for all Presented with severe instrumental ADLs fatigue, anemia, and Med HX- Diabetes, HTN, epistaxis CKD Stage II Currently hospitalized for Expresses high level of workup and treatment t t anxiety re: disease and treatment

60 References Steinman, M.A. etal (2015). How to use the american geriatrics society 2015 Beers criteria- a guide for patients, clinicians, health systems and payors. JAGS 63(1-7) Pergolotti, M. et al. (2015). The prevalence of potentially modifiable functional deficits and the subsequent use of occupational and physical therapy by older adults with cancer. Science Direct,6 ( ) Allart-Vorelli, P, et al. (2015). Haematological cancer and quality of life: a systematic literature review. Blood 305 (10) Sekeres, MA et al. (2004) Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia18, ( ) Deschler, B. et al (2013). Parameters detected t d by geriatric i and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica 98 (2) DeSantis, C.E. et al. (2014). Cancer treatment and survivorship and statistics, CA: A journal for clinicians. 64 (4) Maggior, R.J. et al (2014). Polypharmacy and potentially inappropriate medication use in older adults with cancer undergoing chemotherapy: effect on chemotherapy-related toxicity and hospitalization during treatment. JAGS 62 (8)