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Meet a Young Investigator Young Patients with WM

Jonas Paludo, MD Hematology & Oncology Fellow Mayo Clinic, Rochester - MN

2017 IWMF Educational Forum

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• Relevant conflicts of interest/financial relationship(s)

• None

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Learning Objectives

• Meet a young investigator…

• Review the clinical presentation and outcomes of young patients with WM

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IWWM - 2014

• 2014 International Workshop on WM – London, UK

• Young Investigator Award - Clinical Features and Survival Outcome of Young Patients with WM

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Mayo Clinic – Rochester, MN

,

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Young Waldenstrom

• Dr. Jan G. Waldenstrom, 1944

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WM – Epidemiology

Estimated new cases in 2017

• B-cell lymphoma 80,500

• Non-Hodgkin lymphoma 72,000

• Lymphoplasmacytic lymphoma ~1,100

• Waldenstrom macroglobulinemia ~1,000

• Estimated incidence: 3.5 to 5.5 cases per million-person year

• Almost twice as common in males as females

SEER Cancer Statistics – www.seer.cancer.gov/statfacts Campo E, et al. Blood 2011;117:5019-5032

Groves FD, et al. Cancer 1998;82:1078-1081

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Young Patients with WM

• Median age at diagnosis: ~ 70 years

• ~ 25% younger than 60 years

• ~ 10% younger than 50 years

NCDB database – unpublished data Castillo JJ, et al. Br J Haematol 2015; 169(1): 81-9

Paludo, J. Blood 2016 128:1810

6,200 WM patients

(NCDB database)

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Young Patients with WM

• Most of young WM patients are healthy

• Moderate to severe comorbidities in the general population:

• 18% at 50 years; 37% at 70 years

• Long life expectancy

• At 50 years old: +32 years

Piccirillo JF, et al. Crit Rev Oncol Hematol 2008; 67(2): 124-32. Human Mortality Database. University of California, Berkeley (USA) www.mortality.org

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Young Patients with WM

Paludo, J. Blood 2016 128:1810

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• More than 90% of young WM (≤ 50 years) will succumb from WM-related complications.

Expected Survival

Observed Survival

Median: 11 years of life lost

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Young Patients with WM

• Mayo Clinic experience – 1960 to 2013

• 140 young WM patients (≤ 50 years) compared to 140 older WM patients (≥ 65 years)

Paludo, J. Blood 2016 128:1810

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Young Patients with WM

• Young WM:

• More aggressive variant vs. late presentation (better organ reserve)?

Paludo, J. Blood 2016 128:1810

Young WM Older WM

Smoldering WM 30 pts (21%) 30 pts (21%)

Time from diagnosis to

first treatment (SWM) median 2.4 years median 2 years

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University of Miami

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Young Patients with WM

• Median disease specific survival from first treatment

• Young cohort: 15.6 years; 10-years 77%

• Older cohort: 11 years; 10-years 51%

Paludo, J. Blood 2016 128:1810

Years

Young Cohort

Older Cohort

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Young Patients with WM

• NCDB database: Overall survival from WM diagnosis

• Young cohort: median NR, 10-years 75%

• Older cohort: 8.1 years; 10-years 40%

NCDB database – unpublished data

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Young Cohort

Older Cohort

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Young Patients with WM

• Survival changes over time

Paludo, J. Blood 2016 128:1810

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Years Years

Older Cohort Younger Cohort

1960-1977

1978-1995

1996-2013

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Young Patients with WM

• SEER database analysis by: Nelson et al. (1973-2010) & Castillo et al (1980-2010)

• No survival improvement in young WM patients (≤ 50 years) diagnosed before 2000 compared to after 2000

• Nelson, et al: Median NR vs. 204 months; p=0.53

• Castillo, et al: Median NR vs NR

Nelson S, et al. Blood 2013 122:3135 Castillo JJ, et al. Br J Haematol 2015;169:81-89

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Young Patients with WM

Castillo JJ, et al. Br J Haematol 2015;169:81-89

2001-2010

1991-2000

Years

• Survival changes of young patients with WM

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Rio Grande do Sul - Brazil

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Porto Alegre, RS - Brazil

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Young Patients with WM

• How should we treat young/fit patients with WM??

• Tailor treatment to patient characteristics and preferences

Disease control vs Deep responses

Lower toxicity Continuous treatment Long periods off

any treatment

Higher up-front

toxicity

Convenient

administration Cumulative cost

Limited treatment

duration

Long term side

effects

Long term side

effects?

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Research goals/interests in WM

Treatment strategies

Depth of response

Minimal residual disease?

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Summary

• Young patients with WM are more likely to be diagnosed at a more advanced stage of their disease.

• Although survival rates have improved in WM patients as a whole over the last several decades, no significant improvement in survival of the younger WM population was seen.

• The optimal treatment strategy for young patients with WM is yet to be defined.

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Acknowledgments

• Prashant Kapoor

• Stephen M. Ansell

• Morie A. Gertz

• Robert A. Kyle

• Shaji Kumar

• Nishanth Vallumsetla

• Jithma Abeykoon

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Thank you

paludo.jonas@mayo.edu