Multiple myeloma and its precursor disease (MGUS)

Transcription

1 Review of the Health Effects in Vietnam Veterans Exposed to Herbicides: 11 th Biennial Update Meeting Multiple myeloma and its precursor disease (MGUS) Ola Landgren, M.D., Ph.D. Chief of Myeloma Service, Memorial Sloan-Kettering Cancer Center Professor of Medicine, Weill Cornell Medical College, New York Washington DC, November 30, 2017

2 Multiple myeloma Malignant blood disease Affects ~30,000 Americans every year; about 100,000 are living with myeloma All patients with myeloma previously had monoclonal gammopathy (MGUS) and/or smoldering myeloma* *Most of them are unaware since they were asymptomatic Korde et al. Blood 2011

3 Multiple myeloma precursor disease Monoclonal gammopathy (MGUS) ~1% risk per year* Multiple myeloma Smoldering myeloma ~10% risk per year* *This is on average, but a patient s individual risk can be high vs. low! Korde et al. Blood 2011

4 All multiple myeloma patients previously had MGUS N>77,000 Multiple All had myeloma monoclonal (N=71) gammopathy Landgren et al. Blood 2009

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6 Complex somatic mutational landscape Lohr et al. Cancer Cell 2014

7 Bone and bone marrow abnormalities Hillengass et al. Leuk Lymph 2013

8 Abnormal serum proteins Monoclonal protein Murata et al. (unpublished data)

9 Multiple myeloma outcomes Treatment of myeloma includes combination therapy No established cure yet Average survival used to be less than 3 years, now it is ~10 years (and it is increasing!) Korde et al. Blood 2011

10 Multiple myeloma etiology Excess risk of multiple myeloma among farmers and agricultural workers in cohort and case-control studies Pesticides hypothesized as the basis for these associations US Agricultural Health study suggest excess risk of multiple myeloma among pesticide applicators

11 MGUS and pesticide exposure Landgren et al. Blood 2009

12 MGUS and pesticide exposure Screening of serum from 678 men (30-94 yrs) from Agricultural Health study cohort Serum protein electrophoresis and immunofixation to rule out presence of monoclonal proteins Landgren et al. Blood 2009

13 MGUS and pesticide exposure Prevalence of MGUS 6.8% among subjects 50 yrs or older; 2-fold excess of MGUS (compared to controls) Landgren et al. Blood 2009

14 MGUS and pesticide exposure Chlorinated insecticides Dieldrin, OR=5.6 ( ) (N=6/20 vs 31/649) Fungicides Chlorthalonil, OR=2.4 ( ) (N=10/115 vs 28/561) Landgren et al. Blood 2009

15 MGUS and Agent Orange Landgren et al. JAMA Oncology 2015

16 MGUS and Agent Orange Serum from 479 Ranch Hand veterans Serum from 479 comparison veterans with similar duties in South East Asia but not involved in herbicide spray missions Serum protein electrophoresis, immunofixation and serum free light-chain assays Landgren et al. JAMA Oncology 2015

17 MGUS and Agent Orange Prevalence of MGUS 7.1% versus 3.1%; 2.4-fold excess of MGUS among exposed veterans Landgren et al. JAMA Oncology 2015

18 MGUS and Agent Orange Suggestive association between lipidadjusted TCDD concentration and MGUS Landgren et al. JAMA Oncology 2015

19 MGUS in US population Landgren et al. Leukemia 2014

20 MGUS in US population MGUS prevalence 2.3% in whites 50 yrs or older (blacks 2-fold higher) Landgren et al. Leukemia 2014

21 MGUS in US population MGUS prevalence 3.1% in North/Midwest versus 2.1% in South and West, in NHANES Landgren et al. Leukemia 2014

22 Summary and conclusions

23 Summary and conclusions 2-fold excess of MGUS among pesticide applicators in the US 2.4-fold excess of MGUS among veterans exposed to Agent Orange Population rates of MGUS higher in North/Midwest (vs. South and West)

24 Summary and conclusions These studies support an association between pesticide/herbicide exposure and MGUS Multiple myeloma is consistently preceded by MGUS

25 MSM Myeloma Program & collaborators Myeloma Service Hani Hassoun, MD Alex Lesokhin, MD Nikoletta Lendvai, MD Neha Korde, MD Eric Smith, MD, PhD Sham Mailankody, MD Malin Hultcrantz, MD, PhD Ola Landgren, MD, PhD and team BM Transplant Service Sergio Giralt, MD Heather Landau, MD David Chung, MD, PhD Gunjan Shah, MD and team Immunotherapy Jedd Wolchok lab, MD Molecular Pathology Elli Papaemmanuil lab, PhD Hematopathology Ahmet Dogan lab, MD, PhD Misha Roshal lab, MD, PhD Maria Arcila lab, MD Laboratory Medicine Melissa Pessin lab, MD Katie Thoren, PhD Kaznouri Murata, PhD Cellular Therapy Reneir Brentjens lab, MD, PhD Molecular Imaging Steven Larson lab, MD Wolfgang Weber lab, MD, PhD And many, many more! Funding support

26 Thank you for your attention! Ola Landgren, M.D, Ph.D. Professor of Medicine Chief, Myeloma Service Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065, USA Phone: