Palliative Therapy for the “Incurable” Patient

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 www.seer.cancer.gov; 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. 66% PFS 31% 72% OS 33% MYC pos DLBCL: BCCA analysis • 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 > 1 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;23:5019-5026.

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

10. Age and prognosis PIT Age PS LDH BM + 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) 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 Brentuximabvedotin 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? • 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

13. Domains of palliative care

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 • 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 • A state of excessive anxiety or worry lasting ≥ 6 months • Impacting day-to-day activities Up to 25% of cancer patients experience anxiety Many develop PTSD Barrier to improving the overall cancer experience

15. 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 CollSurg, 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