Blood Cancers in older adultsCancer and Older Adults19 November 2015

Matthew Foster, MDAssistant Professor of MedicineLeukemia, Lymphoma and Myeloma Program

What is leukemia?

• Diverse set of blood and bone marrow cancers

• Can arise from any cell in the blood or bone marrow—myeloid or lymphoid

What is Leukemia?

• Can be acute (i.e. fast onset, rapidly fatal if untreated)

• AML, ALL

• Can be chronic (progresses over years, “die with it, not of it”

• CML, CLL

• Bone marrow cancers without the word “cancer”

• Myelodysplastic syndromes

• Myeloproliferative neoplasms

What is Lymphoma?

What is Multiple Myeloma?

Symptoms of Leukemia

Leukemia in older adults is an unsolved problem

Epidemiology—Acute Myeloid Leukemia

• Median age of AML/MDS at diagnosis:– 65-70 years

(Estey E. JCO 2007; 25(14):1908-15)

• Standard definition of “older” in treatment of AML is ≥ 60 y.o.

Older patients underrepresented in trials

Why the widely discrepant results in older patients??

• Poor performance status (frailty)

• Frequent antecedent hematologic disorder (MDS/MPD)

• Frequent organ dysfunction– Renal dysfunction– Liver dysfuntion– Heart disease

Estey E. JCO 2007; 25(14):1908-15

Disease variables differ in older adults, too

Maslak, P. ASH Image Bank 2001;2001:100215

Impact of cytogenetics on prognosis

Cytogenetic Profile

t(15;17), t(8;21), inv(16)

Normal, all others

Complex (≥ 5 unrelated abnormalities)

-5, -7, 3q abnormalities

Complete Remission Rate

91% 86% 63%

5-Year survival

65% 41% 14%

N=1612 pts

Grimwade et al. Blood. 1998 Oct; 92(7): 2322-33.

Copyright © American Society of Clinical Oncology

Armstrong, S. A. et al. J Clin Oncol; 23:6306-6315 2005

Are these even the same diseases???

Adults Children

Standard treatment for AML…since the 1970’s

•“7+3”—7 days of infusional cytarabine and 3 days bolus anthracycline

• historically 15-30% mortality in older patients•Infections, transfusions, bleeding, GI toxicity

•Allogeneic transplant for high risk•High dose myeloablative chemotherapy unsuited for older patients

What should goals be if this intensive therapy seems too much for older patients?

•Freedom from dependence on transfusions

•Improved infection-related morbidity•Infection prophylaxis•Treatment

•Prevention of complications

•Keeping patients out of the hospital

Palliative-intent, low dose chemotherapy

•European study in 1980’s compared standard chemotherapy with low-dose therapy with palliative intent

•10 week median survival advantage for induction

•Median days of hospitalization were equivalent:

•Palliative Rx: 50

•Induction: 54

Lowenberg et al. JCO 7 (9): 1268. (1989)

Epigenetic approaches for AML and MDS

Methylated genes = silencedDemethylated genes = re-expressed

Egger G et al. Nature (2004) 429; 557-463.

Epigenetic approaches for AML and MDS

Lubbert M et al. J Clin Oncol 29: 1987-1996.

New treatments for particular leukemias--myelofibrosis

Verstovsek S et al. N Engl J Med 2012;366:799-807.

New treatments for particular leukemias--myelofibrosis

Verstovsek S et al. N Engl J Med 2012;366:799-807.

New treatments for particular leukemias—Chronic Lymphocytic Leukemia

Goede V et al. N Engl J Med 2014;370:1101-10.

Patients over 65 with co-existing medical problems

Tedeschi A et al. ASH Annual Abstracts 2015. Abstract no. 495

New treatments for particular lymphomas—Mantle Cell Lymphoma

Kluin-Nelemans HC et al. N Engl J Med 2012;367:520-31.

What are we doing at UNC to improve on this?

Summary

•The majority of blood cancer patients are over age 60

•Older patients have been under-represented in clinical trials for leukemias, lymphoma and myeloma

•Select older patients can be treated as aggressively as younger ones

•A variety of new approaches for patients that might not benefit from standard treatments are being developed

•Clinical trial participation is encouraged!