1. Palliative Therapy for the “Incurable” Patient
Sonali M. Smith, MD
Associate Professor, Section of Hematology/Oncology
Director, Lymphoma Program
The University of Chicago

2. Leading Sites of Cancer Cases and Death

3. Lymphoma Vital Statistics
Cases
Deaths
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
cancer mondial website

4. 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

5. 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

6. MYC pos DLBCL: BCCA analysis
66%
31%
PFS OS
72%
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

7. “Double hit lymphomas”: BCL2 worsens prognosis of MYC pos lymphomas
Prognostic factors for survival Age > 60 yrs PS > High IPI BM pos BCL2 protein pos R-CHOP
Johnson Blood 2009

8. 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:

9. FL has multiple disease states…
Low tumor burden
High tumor burden
Treatment naive
Sensitive
Resistant
Low tumor burden
High tumor burden
1st or 2nd Relapse
Multiply relapsed/refractory
…with different treatment goals

10. Age and prognosis IPI Age PS LDH >1 EN site stage FLIPI-1 Age
LN sites >4
LDH
Stage
Hgb
FLIPI-2
Age
B2M
BM +
LN>6cm
Hgb
MIPI
Age PS
LDH
WBC
(Ki67)
PIT
Age PS
LDH
BM +
The recurrent identification of age as an adverse prognostic factor implies that elderly patients are less “curable” overall

11. New agents challenge our definition of “incurable” and “untreatable”: HL example
Median survival
<8 months after relapse
Brentuximab vedotin
Med survival 22 months
OS and PFS after ASCT in r/r HL
Younes JCO 2012; Lavoie Blood 2005

12. When does the change to palliative approach occur?
Living with cancer
Dying with cancer
Loss of marrow reserve
Worsening comorbidities due to disease
Irreversible toxicity due to treatment
Change in performance status
Patient/family request

13. Domains of palliative care
Anxiety
Depression
Anorexia
Pain control
Nausea/vomiting
Diarrhea
Constipation

14. Emotional aspects of palliative care and impact on treatment goals
Anxiety
Generalized anxiety disorder
Panic attacks
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
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
Up to 25% of cancer patients experience anxiety
Many develop PTSD
Barrier to improving the overall cancer experience

15. Anorexia Cachexia – wasting syndrome Impact  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.

16. 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

17. 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

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

19. Important tools when approaching pts with palliative intent
Symptom control is key
Steroids
Radiation
Multidisciplinary approach

20. 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