Palliative Therapy for the “Incurable” Patient

Sonali M. Smith, MDAssociate Professor, Section of Hematology/Oncology

Director, Lymphoma Program The University of Chicago

Leading Sites of Cancer Cases and Death

Lymphoma Vital Statistics

www.seer.cancer.gov; cancer mondial website

Cases DeathsTotal Male Female Total Male Female

USA 75,190 40,880 34,310 20,620 10,510 10,110

EU 52,440 28,043 24,397 25,906 13,285 12,261

France 8375 4471 3904 4212 2225 1987

Germany 10,179 5203 4976 5260 2501 2759

Italy 10,825 5906 4919 4675 2390 2285

UK 8307 4515 3792 4507 2380 2127

What is an “incurable” lymphoma?

• Newly diagnosed: double hit• All indolent lymphomas and CLL• Relapsed/refractory aggressive

lymphomas in the elderly• Multiply relapsed and/or refractory disease

in the young• Mantle cell lymphoma• Most T-cell lymphomas

What is an incurable lymphoma?

• 41 yo woman with MYC+BCL2+ B-cell lymphoma unclassifiable (BCLU) who progresses through DA-EPOCH-R with a large breast mass

• 78 yo man with MCL since 2005 s/p R-HyperCVAD, bortezomib, BR, temsirolimus, DHAP who has persistent cytopenias due to marrow involvement

• 92 yo man with DLBCL who relapses 8 months after R-CHOP (with dose reductions)

• 67 yo woman with FL since 2008 who has no symptoms but with radiographic progression after 2 prior lines of therapy

Biology

Cumulative toxicity

Advanced age

Histology

MYC pos DLBCL: BCCA analysis

66%

31%PFS

OS72%

33%

• Patients with MYC pos DLBCL had inferior PFS and OS

• Even when excluding BCL2 pos cases, MYC was an adverse prognostic factor

• 2 of 12 (17%) of patients with MYC pos DLBCL had CNS recurrence compared to 4 of 123 (3%) of MYC neg DLBCL

Savage Blood 2009

“Double hit lymphomas”: BCL2 worsens prognosis of MYC pos lymphomas

Prognostic factors for survival Age > 60 yrs PS > 1

High IPI BM pos

BCL2 protein pos R-CHOP

Johnson Blood 2009

FL is an incurable lymphoma

• Goals of therapy change over time

• Selection of any treatment must reflect short- and long-term goals

• Can be difficult to identify when patient should move to palliative care

Swenson WT et al. J Clin Oncol. 2005;23:5019-5026.

FL has multiple disease states…

Treatment naive

1st or 2nd Relapse

Multiply relapsed/refractory

Low tumor burden

High tumor burden

Low tumor burden

High tumor burden

Sensitive

Resistant

…with different treatment goals

Age and prognosis

IPIAge PS

LDH>1 EN site

stage

FLIPI-1Age

LN sites >4LDH

StageHgb

FLIPI-2Age B2MBM +

LN>6cmHgb

MIPIAge PS

LDHWBC(Ki67)

PITAge PS

LDHBM +

The recurrent identification of age as an adverse prognostic factor implies that elderly patients are less “curable” overall

New agents challenge our definition of “incurable” and “untreatable”: HL example

OS and PFS after ASCT in r/r HL

Younes JCO 2012; Lavoie Blood 2005

Median survival

<8 months after relapse

Med survival 22 months

Brentuximab vedotin

When does the change to palliative approach occur?

• Loss of marrow reserve• Worsening comorbidities due to disease• Irreversible toxicity due to treatment• Change in performance status• Patient/family request

Living with cancer

Dying with cancer

Domains of palliative care

Domain

Anxiety

Depression

Anorexia

Pain control

Nausea/vomiting

Diarrhea

Constipation

Emotional aspects of palliative care and impact on treatment goalsAnxiety

• A state of feeling apprehension, uncertainty or fear

• May lead to some level of dysfunction

• A state of excessive anxiety or worry lasting ≥ 6 months

• Impacting day-to-day activities

Generalized anxiety disorder

• Sudden onset of intense terror, apprehension, fearfulness, terror or felling of impending doom

• Usually occurring with symptoms (Shortness of breath, palpitations, Chest discomfort, Sense of choking, Fear of going crazy or losing control

• Lasts15 – 30 minutes

Panic attacks

1. Up to 25% of cancer patients experience anxiety

2. Many develop PTSD3. Barrier to improving the overall

cancer experience

Anorexia

Cachexia – wasting syndrome• Lean tissue• Performance status• Altered resting energy expenditure• Appetite

Impact• ≥ 5% weight loss and poor prognosis • Trend toward lower chemotherapy response rates• Anorexia and poor prognosis• QOL, function• Affects caregivers

MacDonald N, et al. J Am Coll Surg, 2003.Dewys WD, et al. Am J Med, 1980.

Loprinzi CL, et al. JCO, 1994.

Timing of palliative care initiation• Generally done too late

– 60% of cancer pts hospitalized in last month of life– 25% of US cancer pts die in the hospital– Median length of time between hospice referral and death is 33

days• Not clearly documented

– Fragmented health care systems• Need better tools to recognize when patients have 6 months (not

days, weeks) to live before making palliative care the dominant aspect of pt care– Only 32% of physicians accurately predicted shortened life

expectancy– Consistently overestimated survival

Timing of shift to palliative care is important

• Timely recognition of poor prognosis led to – less ‘aggressive’ end‐of‐life care – earlier hospice referrals– improved anxiety, less depression, and improved

quality of life compared• Disconnect between patient desire and physician goals

– Occasionally, disconnect between patient perceptions and reality

Delayed recognition leads to increased suffering and increased socioeconomic burden

Model of palliative care

Rocque, G. B. & Cleary, J. F. Nat. Rev. Clin. Oncol. 10, 80–89 (2013)

Important tools when approaching pts with palliative intent

• Symptom control is key• Steroids• Radiation• Multidisciplinary approach

Palliative care in the “incurable” patient: take-home points

• Death from lymphoma is an important and still common occurrence• Many lymphomas are inherently or progressively incurable as

defined by – Biology– Advanced age– Cumulative toxicities– Histology

• Important to recognize when the goal of treatment is palliative – Symptom management is critical – Particularly challenging in indolent NHL– Need to discuss with patient/family– Need to clearly document the goals of treatment