Living Well With Myeloma: Can Nutrition Improve Quality of Life and Outcomes in Myeloma?

Thank you for Joining!

Can Nutrition Improve Quality of Live and Outcomes in Myeloma?

Living Well with Myeloma – Can Nutrition Improve Quality of Life and Outcomes in Myeloma?

Urvi A. Shah, MD Assistant Attending, Myeloma Service

@UrviShahMD October 12, 2023

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Disclosures Research Funding (to institution)

Honoraria

Celgene/BMS

MJH Life Sciences

Janssen

Janssen ACCC

Advisory Board

MashUpMD

Janssen

RedMedEd

BMS

i3Health

Sanofi Medical Advisory Board (uncompensated) Plant Powered Metro New York

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

3

My Background Grant Medical College, Mumbai

Tufts Medical Center, Boston

Montefiore Medical Center, New York

Memorial Sloan Kettering Cancer Center, New York

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

Nutrition Intervention (NUTRIVENTION) Research at MSK Research program at MSK to study nutrition, microbiome and metabolism in myeloma.

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

5

Outline Lifestyle Considerations for Quality of Life Comorbidities Lifestyle Research and its Implementation in Plasma Cell Disorders is an unmet need

• Obesity • Diabetes Mellitus • Cardiovascular disease • Renal disease

Nutrition Research • Dietary Patterns • Interventional Trials – NUTRIVENTION

Practical Nutrition Tips Some Myths

• Microbiome

Kim et al BMJ NPH 2021 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

6

Patients with myeloma are living longer than ever before

There is an opportunity to improve outcomes and quality of life further with dietary and lifestyle interventions.

Shah UA, Mailankody S. BMJ 2020 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

7

Healthy Lifestyle and Genetic Risk in Colorectal Cancer UK Biobank Cohort 346,297 participants 2066 colorectal cancer cases Healthy Lifestyle Score (sum of body fat, physical activity, sedentary time, diet, alcohol, smoking) Polygenic Risk Score (genetic risk score) Healthier lifestyle associated with reduced risk of colorectal cancer High genetic risk patients could benefit more from lifestyle modification than those in low genetic risk

Choi et al AJCN 2021 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

8

66-year-old male with multiple myeloma Past Medical History

• Kidney stone

Coronary Artery Disease

• Hyperthyroidism

Atrial fibrillation

• Multifocal pneumonia

Neuropathy

• Type 2 DM

Hypertension

• Congestive heart failure

Hyperlipidemia

• Preglaucoma

Stroke with weakness in wheelchair

• left lower lymphedema from CABG.

Deep vein thrombosis Sleep apnea

Past Surgical History

Morbid Obesity

• Right knee repair

Major depressive disorder

• Right knee joint replacement surgery Umbilical hernia repair

Frequent hospital admissions Cognitive decline/dementia Degenerative joint disease Cellulitis Abdominal hernia © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

• Tonsillectomy x 2

Comorbidities

Therefore, not a candidate for: Stem cell transplantation CAR T cell therapy Clinical trials Some intensive chemotherapy Thus, decreased overall survival.

• Cardioversions x 10 • Multiple cardiac ablation.

• Coronary Artery Bypass Graft

@UrviShahM D

9

75-year-old male with multiple myeloma IgG kappa and free kappa ISS stage I, RISS stage I multiple myeloma Treated with 6 cycles of daratumumab, lenalidomide and dexamethasone Followed by lenalidomide maintenance Achieved complete response

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Comorbidities

Past Medical History Coronary Artery Disease Atherosclerosis Hyperlipidemia Prediabetes Depression Past Surgical History Gall bladder removal surgery

Although multiple myeloma was in remission died of a cardiac arrest.

@UrviShahM D

10

Comorbidities

Extreme Body Mass Index

1,120 patients with MM in CoMMpass Registry

MGUS (OR 1.8) Overall Survival

Landgren et al Blood 2010

MGUS progression to MM (HR 1.9-2.6) Thordardottir et al Blood Advances 2017; Chang S-H et al JNCI 2017

MM (OR 1.2-1.4) Birmann et al CEBP 2017; Samanic et al CCC 2003

Death in MM (HR 1.4-1.8) Calle et al NEJM 2003; Teras BJH 2014

Underweight vs. Normal: HR: 2.32; 95% CI: 1.09, 4.97 Severe obese vs. Normal: HR: 1.43; 95% CI: 0.98-2.08

Shah UA et al. Blood Cancer J 2023

Characteristic Parekh et al. Leukemia 2021

However, patients that lose weight unintentionally due to a myeloma diagnosis are likely to do worse (HR 1.6) Beason et al Oncologist 2013 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Weight loss (≥5%) Weight stable (<5%) Weight gain (≥5%)

15%

Under Weight (4) 0%

Normal BMI (85) 6%

Over weight/ Obese (284) 19%

62%

50%

67%

64%

18%

50%

27%

16%

Overall (389)

pvalue 0.003

Thirugnanasambandam, Firestone et al. IMS 2023

@UrviShahM D

11

Diabetes Mellitus

Comorbidities

• DM ↑ risk of cancer, hematologic cancer & myeloma Gong et al Diabetologia 2021; Dankner et al AJE 2016;

• DM ↑ risk of MGUS & myeloma within 6 months of DM diagnosis but not after. Maybe detection bias.

Shah UA et al Haematologica 2021

Gong et al Diabetologia 2021

• Retrospective study from MSK and Mount Sinai • N=5383 patients • In MM, diabetes is more prevalent in Black patients (25%) compared to White patients (12%) • DM associated with worse survival (p<0.001).

• In a mouse model of type 2 diabetes the progression of MM is faster in mice with diabetes than mice without diabetes (p<0.05).

Shah U et al. Blood Advances 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

12

Dietary changes after a cancer diagnosis

Nutrition

421 patients with plasma cell disorders surveyed via HealthTree Foundation Since your diagnosis, have you had questions about diet and nutrition?

82%

Oncologist did not address it

57%

If your oncologist gave you recommendations, did you attempt to follow them?

94%

Patients' self reported (pre versus post diagnosis) – • Increase in fruits, vegetables, whole grains, plant proteins, seafood consumption (p<0.0001) • Decrease in red meat and junk food consumption (p<0.0001) Malik M et al. Blood Cancer J 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

13

World Cancer Research Fund Guidelines

Nutrition

AICR

Although ACS/AICR have published dietary guidelines, only 34% of respondents were aware of these guidelines, and of this group 47% attempted to follow them

Malik M et al. Blood Cancer J 2022; https://www.aicr.org/cancer-prevention/food-facts/ © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

14

Nutrition

Prediagnosis Dietary Patterns and Myeloma

Nurses’ Health Study 116,777 women + Health Professionals Study 49,019 men; 423 MM

Vegans/vegetarians had 77% less MM than meat eaters

EPIC Oxford + Oxford Vegetarian Cohort 61,647 people; 65 MM

Prediagnosis Dietary Pattern Alternate Healthy Eating Index-2010 (AHEI)

(RR 0.23)

15-24% lower MM deaths

Alternate Mediterranean Key, Am J Clin Nutr 2014

Dietary Approaches to Stop Hypertension (DASH) diet Prudent diet

16-24% higher MM deaths

Western diet

NIH AARP study 392,589 participants; 1,366 MM

Higher healthy plant-based diet index associated with 15% reduced risk of MM development HR (Q4 vs Q1): 0.85; 95% CI: 0.73, 1.0; p=0.043 No association with Healthy Eating Index 2015, Healthy Diet Score and Alternate Mediterranean diet score

Castro, Parikh et al. ASCO 2023; MedRxiv 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Empirical Dietary Index for Insulin Resistance (EDIR) Empirical Dietary Index for Hyperinsulinemia (EDIH)

NHANES study 373 MGUS; 1406 controls

Lee et al IJC 2020

Food/Beverage Group

MGUS (N=373)

Whole-grain bread, oats, rice Fruits, vegetables Tomatoes Cruciferous vegetables* Sugar-sweetened beverages Soft drinks, sugar-sweetened Soft drinks, artificially sweet Cola

0.70 (0.48-1.01) 0.69 (0.52-0.93) 0.72 (0.51-1.00) 0.44 (0.26-0.74) 1.34 (1.00-1.78) 1.41 (1.01-1.96) 1.55 (1.04-2.33) 1.59 (1.14-2.22)

Odds ratios (95% confidence intervals); *such as: broccoli, cauliflower, cabbage, kale, arugula, brussels sprouts Joseph et al. IMS 2023; MedRxiv 2023

Dietary Mechanisms

Nutrition

Shah UA et al. JAMA Oncology 2022 and Shah UA et al Leukemia 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

16

Microbiome in Humans

Nutrition

Number of human and bacterial cells in the body Human = 30 trillion Bacteria = 38 trillion

Sender et al. PLOS Biology 2016; Valdes et al BMJ 2018 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

17

Nutrition

Factors That Influence Microbiome and Immune Response Non-Modifiable Factors

Modifiable Factors

Age Gender Race/Ethnicity Genetics Infections Vaccination Medical Conditions Cancer Rural/Urban Environment

Nutrition/Dietary Patterns Obesity Diabetes Mellitus Physical Activity Sleep Stress Smoking/Alcohol/Drugs Medications

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

18

Gut microbiome and immune system

Nutrition

• Gut microbiome alpha diversity: Diversity of bacterial species within the gut microbiome of the same individual • Short chain fatty acids: Fatty acids produced when gut bacteria ferment fiber.

The most common types are butyrate, propionate, and acetate.

• Butyrate: Butyrate has been associated with anti cancer and anti-inflammatory properties.

• Butyrate producers: Gut bacteria that produce butyrate.

Kim et al. Trans Med Aging 2020 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

19

Microbiome Diversity is associated with Survival

Khan et al. Blood 2021; Peled et al. NEJM 2020 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

20

Diet and COVID19 Severity In 2884 front-line healthcare workers from six countries (France, Germany, Italy, Spain, UK, USA) Individuals on plant-based diets higher in vegetables, legumes and nuts, and lower in poultry and red and processed meats, had 73% lower odds of moderateto-severe COVID-19

Kim et al BMJ NPH 2021 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

21

Diet and COVID19 Severity 592,571 participants - smartphone-based COVID-19 Symptom Study (UK and USA) 31,815 COVID-19 cases were documented hPDI: healthful Plant-Based Diet Index.

Healthy plant-based diet was associated with lower risk and severity of COVID-19.

Merino et al. BMJ Gut 2021 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

22

Nutrition

Rethinking Diet as a Drug?

Prevention

Treatment

Survivorship

Dietary therapies as backbone

Synergy with - Checkpoint inhibitors - Bispecific antibodies - CAR T cells - Monoclonal antibodies - Vaccines - Immunomodulatory drugs - Chemotherapies

In combination with maintenance therapy or as single agent

Reducing the risk of development of a primary or secondary cancer.

Prevent other medical problems and cancers.

Fewer comorbidities means fewer side effects and ability to give full dose treatment.

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Decreasing the likelihood of a relapse once in remission.

Reduce the risk of other medical problems and cancers.

@UrviShahM D

23

Nutrition

Given early detection, as hematologists and oncologists, we have an

Opportunity for Secondary Prevention Prevention Dietary therapies as backbone Reducing the risk of development of a primary or secondary cancer.

Prevent other medical problems and cancers.

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Monoclonal Gammopathy

Smoldering MM

Immune Function

Multiple Myeloma

Genomic Alterations

@UrviShahM D

24

Tilting the Scale for Myeloma Development

Nutrition

In the US population, 70% have an elevated BMI and 45% are prediabetic/diabetic Additionally, ≥3% of the population ≥50 years has MGUS/SMM Normal weight MGUS/SMM with an elevated BMI are twice as likely to progress to MM ↑ risk 1.1-2.6 Landgren Blood 2010 Teras BJH 2015 Birmann CEBP 2017 Chang JNCI 2017; Thordardottir Blood Adv 2017 Dankner AJE 2015 Shah UA et al, Haematologica 2021 Lee JNCI Can Spec 2019 Lee IJC 2020 Pianko Lesokhin Bld Adv 2019

Obesity Diabetes Mellitus Inflammatory Diet Western Diet Altered Microbiome

Obesity Diabetes Mellitus Inflammatory Diet Western Diet Altered Microbiome

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

MYELOMA DEVELOPMENT

Normal blood sugar Plant forward diets Diverse healthy microbiome

↓ risk 0.23-0.76 Lee IJC 2020 Key AJCN 2014 Thordardottir Plos One 2018 Vlajinac Neoplasma 2003 Hosgood CCC 2007 Chatenoud Int J Cancer 1998 Pianko Lesokhin Bld Adv 2019 Shah UA et al. Clin Can Res 2022

MYELOMA PREVENTION Whole foods plant-based diet Prebiotics

Normal weight Normal blood sugars Plant forward diets Diverse healthy microbiome @UrviShahM D

25

Nutrition

NUTRIVENTION Trial and Demographics Blood, Stool, Imaging, Bone Marrow

Blood Stool

Blood Stool

Screening and Enrollment

Week 4

Week 8

Week 12

Blood Stool

Week 24

Blood, Stool, Imaging, Bone Marrow

Week 52

Whole foods plant-based meals (Plantable) Dietary survey

Nutrition coaching (Plantable health coach & MSK dietitian)

Dietary survey

MGUS/SMM; BMI≥25 N=20 NCT04920084 • 3 patients dropped out during 12-week intervention and were replaced.

• 2 patients were lost to follow up after 12 weeks and were not replaced.

• 18 patients completed 1 year on study in September 2023

Median Age, years Sex Male Female Race Non-Hispanic White Black/Other/Hispanic Diagnosis MGUS SMM BMI Category Overweight (BMI 2529.9) Obese 1 (BMI 30-34.9) Obese 2 (BMI 35-39.9) Obese 3 (BMI 40+) Diabetes/Prediabetes Yes No

62 (40-79) 43% 57% 57% 43% 52% 48% 26% 35% 22% 17% 26% 74%

Shah UA et al. ASH 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

26

Nutrition

Dietary Adherence and Quality of Life • Meets feasibility endpoint (mean adherence >70% at 12 weeks) • Patients were eating to satiety with no calorie restriction • Mean calorie reduction (baseline to 12 weeks): 547 cal EORTC QLQ C30 A significant improvement in • Global health status (p=0.03) • Dyspnea (p=0.001) • Fatigue (p=0.06)

EORTC QLQ C30 Global health status / QoL Symptom scales / items Fatigue Dyspnoea QLQ Total score

Baseline 66.7

Median Post 12week intervention 83.3

33.3 33.3 81.9

22.2 0 86.1

Linear Mixed Model Fit Estimate Change/month p value 71.5 0.68 0.03 26.7 23.8 82.6

-0.7 -1.3 0.16

0.06 0.001 0.39

@UrviShahM D

27

Shah UA et al ASH 2022 and IMS 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Nutrition

Metabolic and Microbiome Results

• Higher adiponectin leptin ratio implies less insulin resistance.

Baseline Post 12week intervention p value Median Median BMI (kg/m2) 20 34.3 32.1 0.00009 LDL (BL >100 mg/dL) 14 133 101 0.003 Triglycerides (BL >150 mg/dL) 3 175 74.5 0.5 HgbA1c (BL > 5.7%) 6 5.95 5.25 0.06 Insulin 20 6.34 4.12 0.01 Adiponectin/Leptin Ratio 20 0.14 0.19 0.0002 IGF-1 (ng/mL) 20 123.7 115.6 0.43 CRP BMI: (BLBody >0.5 mg/dL) 7 0.98 0.15 0.8 Mass Index; LDL: Low density lipoprotein cholesterol; IGF-1: insulin like growth factor; CRP: C reactive protein; BL: baseline; IQR: Inter Quartile Range Metabolic Biomarker

Gut Microbiome Diversity

Shah UA et al. ASH 2022 and IMS 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

12 weeks

12 weeks

• Low adiponectin, high leptin and high insulin are associated with myeloma progression.

• Improved gut microbiome diversity and butyrate producers

N

Gut Microbiome Butyrate Producers

• Meets its weight loss feasibility endpoint (BMI reduction >5% at 12 weeks)

12 weeks

12 weeks

@UrviShahM D

28

Nutrition

Two patient examples on the study

71-yo M (Mayo Int Risk IgGκ/IgGλ MGUS) Biomarker BMI (kg/m2) HgbA1c (%) Insulin (mU/mL) IGF-1 (ng/mL) Adiponectin/Leptin Ratio Stool Butyrate Bone Marrow Plasma Cells Type 2 Diabetes Mellitus

Baseline 28.9 4.7 13.9 310.6 0.42 18.08 <5%

12 weeks % Change 25.2 13%↓ 4.7 0% 2.9 79%↓ 244.2 21%↓ 0.77 82%↑ 19.32 7↑ 5-9% 0-50%↑ (18m)

61-yo F (IMWG Int Risk IgGκ SMM) Biomarker BMI (kg/m2) HgbA1c (%) Insulin (mU/mL) IGF-1 (ng/mL) Adiponectin/Leptin Ratio Stool Butyrate Bone Marrow Plasma Cells

Baseline 12 weeks % Change 38.8 34 13%↓ 5.1 5.2 0% 6.6 7.6 (not fasting) 18%↑ 127.1 86.6 32%↓ 0.41 0.56 37%↑ 11.72 33.45 185↑ 20-30% 10-15%, t(6;14) (12m) 50%↓

Stopped insulin detemir 2 weeks into study and been off ever since

M spike 0.24 02/2016

M spike 1.2 07/2021

M spike 1.28 01/2023

M spike 0.72 03/2015

M spike 1.2 07/2021

M spike 1.24 10/2022

Shah UA et al. IMS 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

29

“It looked pretty dark back in 2010. Thanks to this trial, I’m into the light.”

Nutrition

NUTRIVENTION trial Before NUTRIVENTION

After NUTRIVENTION

https://www.mskcc.org/msk-news/summer-2023/food-as-medicine-why-one-doctor-thinks-dietcould-help-control (with patient permission) © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

30

Post-Intervention Survey Survey sent to 17 patients who completed study and alive; 14 responses received During the dietary intervention, did you notice changes in any of the following?

Displayed in order of improvement 0%10%20%30%40%50%60%70%80%90% 100% High Body Weight Diabetes/Pre-Diabetes

Heartburn, reflux, bloating Hypertension Arthritis/Joint/Back Pain Excessive sleep No Change

• All patients reported they would sign up again for the intervention (14 yes, 0 no) • 4 patients reported they were able to stop medications, saving an average of $62.50 per month (range $20-100)

Lack of energy

Improved

• All patients reported the intervention to be easy to follow (7 very easy, 7 somewhat easy, 0 somewhat difficult, 0 very difficult)

Worsened

Shah UA et al. Unpublished data © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Not Applicable

“I was able to attain a healthy weight and have maintained the weight since starting the meals. I feel good, have energy and no bloating.”

– NUTRIVENTION Patient @UrviShahM

NUTRIVENTION-3 Trial is Enrolling

Nutrition

Q: Impact of dietary vs supplementary vs placebo interventions on the microbiome especially butyrate producers in MGUS and SMM patients

MGUS/SMM N=150 NCT05640843 Currently enrolling at MSK in NYC Participant needs 6 visits to MSK spread over 12 months of the trial once enrolled.

Shah UA et al. ASH 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

32

Telehealth National Study In Collaboration with HealthTree Foundation

NUTRIVENTION-2 Trial to Open This Year SMM patients (n=100) Randomized and stratified based on BMI normal vs elevated and location rural vs urban

-1

Eligible if you have • Smoldering Myeloma • Live in the United States • Scan the QR code

1 week no intervention

0

1

WFPBD meals + Nutrition Counseling 2 weeks (n=25)

Probiotics

Omega 3

Curcumin

2 weeks (n=25)

2 weeks (n=25)

2 weeks (n=25)

2 Stool Collection timepoints: -1, 0, 1, 2 weeks (Microbiome)

Castro F et al. ASH 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

33

Dietary Synergism with Conventional Therapies Treatment Synergy with - Checkpoint inhibitors - Bispecific antibodies - CAR T cells - Monoclonal antibodies - Vaccines - Immunomodulatory drugs - Chemotherapies Fewer comorbidities means fewer side effects and ability to give full dose treatment.

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Diet + Drug?

Drug?

Nutrition

Additive or synergistic activity of diet with standard of care?

Improved • MRD Negativity?

• PFS? • OS? • Quality of Life?

@UrviShahM D

Nutrition

IDEAL Trial in High-Risk Acute Lymphoblastic Leukemia • 40 patients • Newly diagnosed • Prospective, nonrandomized, single arm study compared to historical control • 20% caloric deficit - 10% reduced calorie intake and 10% increased exercise • USDA MyPlate and Traffic Light • 28 days during cycle 1 • Primary endpoint: % change in fat mass during induction • NCT02708108

Orgel et al. Bld Adv 2021 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

35

Nutrition

Dietary Fiber and Mediterranean Diet in Melanoma (skin cancer) • • • •

• • • • •

Melanoma on immune checkpoint blockers 128 patients High dietary fiber without probiotics Improved PFS

Advanced melanoma received immune checkpoint blockers 91 patients Mediterranean diet (whole grains, fish, nuts, fruit, and vegetables) Increased ORR Improved 12-month PFS

Spencer et al. Science 2021; Bolte et al. JAMA Oncol 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

Neutro-Diet Trial

Non-Restrictive Diet allowed fresh fruit and vegetables Stella et al. Bld Adv 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

37

Nutrition

Dietary Interventions to Improve Survival Survivorship

No Maintenance

In combination with maintenance therapy or as single agent

Diet and Lifestyle?

Decreasing the likelihood of a relapse once in remission.

Maintenance Drug

Reduce the risk of other medical problems and cancers.

Maintenance Drug, Diet and Lifestyle?

First Remission

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

First Relapse

@UrviShahM D

Diet, Microbiome and Sustained MRD Negativity Clinical trial at MSK

Nutrition

Data collection

MM on Lenalidomide Maintenance therapy Lenalidomide 10 mg 21/28 days for 5 years

Correlate

• •

Dietary HEI2015 Flavonoids

• • •

Microbiome

Diversity Relative abundance of butyrate producers Stool metabolite levels

•

Outcomes Sustained MRD negativity

Shah UA et al. Clin Can Res 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

39

Nutrition

Diet & Microbiome Correlate with Sustained MRD Negativity Diversity

Butyrate Producers

Healthy Eating Index 2015 Butyrate level at 3m Sustained MRD-negativity R p-value p-value Total Protein 0.5 0.004 0.02 Seafood and Plant Protein 0.45 0.009 0.02

Butyrate Concentration

Total Dietary Flavonoids Total anthocyanidins Total flavones Total flavanols Dietary Flavonoid Diversity Index

Butyrate level at 3m R p-value 0.47 0.01 0.48 0.01 0.42 0.02 0.46 0.008

Shah UA et al. Clin Can Res 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

40

Hypothesis and Mechanisms for this Correlation

Nutrition

Enrolling at MSK (NYC) - NCT04497961 Primary Endpoint: Quality of Life Shah UA et al. Clin Can Res 2022 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

41

Trivia Time Food Group

How much do Americans eat on average?

How much should Americans eat?

Example

Added Sugar

17 teaspoons/day

6 (F) or 9 (M) teaspoons/day

10 tsp in 1 Coke 12 oz can

Dietary Fiber

10-15 grams/day

25 (F) or 38 (M) grams/day

1 cup cooked pinto beans = 15g

Salt

3,400 mg

<2,300 mg (1 teaspoon)

70% comes from prepared foods Chicken is 8th most common source

Fruits

0.9 cups/day

1.5 (F) or 2 (M) cups/day

1 large banana = 1 cup

Vegetables

1.4 cups/day

2.5 (F) or 3.5 (M) cups/day

1 cup broccoli = 35 calories

Protein

80-100 grams/day 16% of calories

48-72 grams/day 10% of calories

1 cup cooked pinto beans = 15g

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

42

CardioSmart.org/sugars © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

43

The Fiber Gap

Nutrition

Recommended Daily Intake: 30 grams from food sources (only plants)

THE FIBER GAP 67% consumers believe they meet their fiber needs (International Food Information Council)

In reality, only 5% do so!

(2009-2010 NHANES survey data)

Desai et al Cell 2016 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

44

Fiber Requirements (example) Recommended daily intake = 30 grams (Males = 38 grams; Females = 25 grams)

Fiber

Western diet

High fiber diet

Breakfast

1 egg = 0g 3 strips bacon = 0g 1 slice wheat bread = 1g

1 cup cooked oatmeal = 4g 1 tbsp peanut butter = 1g

Lunch

Small chicken breast = 0g 1 bag frozen broccoli = 12g

1 bag frozen broccoli = 12g 1 cup lentils = 16g 1 cup brown rice = 4g

Dinner

Beef 1 serving = 0g 1 cup white rice = 1g 1 baked potato = 3g

1 cup black beans = 15g 1 medium ear corn = 2g 1 avocado = 9g

Snack

1 cup yogurt = 0g 1 slice cheese = 0g

1/4 cup almonds = 5g 1 banana = 3g

TOTAL fiber

17g

71g

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

45

Protein Requirements (example) Recommended daily intake = 0.8-1.2 g/kg

Protein

Western diet

High fiber diet

Breakfast

1 egg = 6g 3 strips bacon = 12g 1 slice wheat bread = 3g

1 cup cooked oatmeal = 6g 1 tbsp peanut butter = 4g

Lunch

Small chicken breast = 23g 1 bag frozen broccoli = 7g

1 bag frozen broccoli = 7g 1 cup lentils = 18g 1 cup brown rice = 4g

Dinner

Beef 1 serving = 34g 1 cup white rice = 4g 1 baked potato = 4g

1 cup black beans = 15g 1 corn on the cob = 5g 1 avocado = 3g

Snack

1 cup yogurt = 9g 1 slice cheese = 4g

1/4 cup almonds = 8g 1 banana = 1.5g

TOTAL protein

106g

72g

60 kg person = 48-72 grams

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

46

Animal or Plant Protein?

131,342 participants Cohort study High intake of animal protein was positively associated with mortality, with the inverse true for high intake of plant protein, especially among individuals with at least 1 lifestyle risk factor.

Song et al. JAMA 2016 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

47

Amino Acid Composition of Various Proteins

Gardner et al. Nutr Rev 2019 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

48

Whole Grains and Cancer Risk • 640,065 participants and 34,346 cancer deaths Every 3 servings/day increase associated with  17% decrease in colorectal cancer risk  15% decrease in total cancer mortality • 1,575 participants and 174 colorectal cancer deaths Every 20 g/day increase associated with  18% decrease in cancer specific mortality Aune et al, BMJ 2011 Aune et al, BMJ 2016 Song et al, JAMA Oncol 2017

• Recommended daily intake

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

49

Nutrition

How Many Different Plant Foods Do You Eat in a Week?

Stool samples from >10,000 individuals >30 plant foods associated with • ↑ Microbiome diversity • ↓ Antibiotic resistance genes • ↑ Conjugated linoleic acid abundance (polyunsaturated fatty acid with anti cancer and fat reducing properties)

McDonald et al mSystems 2018 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

50

Plant based diets can be many of many varieties VEGAN

VEGETARIAN

HIGH-FIBER PLANT BASED

Zero animal products.

Some animal products.

Minimal animal products.

Ethical and environmental reasons.

Ethical or religious reasons.

Health reasons.

No meat, fish, eggs, dairy.

No meat or fish.

Eggs and dairy allowed.

Doesn’t have to be healthy but can be very healthy.

Doesn’t have to be healthy but can be very healthy.

Focus on whole foods & mainly plants, avoids processed foods.

Healthy.

Whole Food Plant-based Vegan Whole Food Plant-based Vegetarian Whole Food Plant-based Pescatarian Whole Food Plant-based Mediterranean Whole Food Plant-based Paleo Whole Food Plant-based Low Carb © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Whole Food Plant-based Keto

@UrviShahM D

Understanding calorie density instead of calorie counting

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

52

Organic Food and Cancer Risk

Nutrition

68 946 participants, 1340 first incident cancer cases.

French Study NutriNetSante Cohort

Baudry et al. JAMA Int Med 2018 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

53

Should you eat only organic foods?

Nutrition

If one-half of the U.S. population were to increase fruit and vegetable consumption by 1 serving/day each, an estimated 20,000 cancer cases might be avoided each year.

In contrast the pesticide residues on those fruits and vegetables might result in up to about 10 additional cancer cases/year. https://www.safefruitsandveggies.com/pesticide-residue-calculator/ Reiss et al Food and Chem Toxic 2012 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

54

Vitamin D deficiency ↓ overall survival (n=1889)

Mohr et al JSBMB 2014

40% deficient, 35% insufficient 25% normal (n=100)

↑ CRP (inflammation), ↑ creatinine, ↑ ISS stage (n=148)

↑ severe neuropathy due to bortezomib and thalidomide (n=111)

↑ plasma cells in BM (n=83)

Can precipitate severe hypocalcemia with bisphosphonates/ denosumab

↓ bone turnover and ↓ bone density (n=108)

↓ progression free and overall survival post transplant (n=183)

↓ solar UVB rays ↑ MM ? ↓Vit D

Ng et al Am J Hematol 2009

Yellapragada et al. Blood Adv 2020

Badros et al BJH 2008

Lauter et al Can Inv 2015

Wang et al Supp Care Cancer 2016

Diamond et al. AJH 2009

(several case reports)

Eicher et al Hematologic Oncology 2020

Burwick Ann Hematol 2017 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

55

Discussing Nutrition Must Be Individualized

Nutrition

• Disease Stage – Newly diagnosed, on maintenance, relapsed • Patient Choice – Receptive to hearing about this and empowered by it or overwhelmed and would not help • Medical issues related to the cancer – Do they have significant weight loss from their cancer and side effects to treatment like nausea and diarrhea that they aren’t tolerating most foods.

• Medical issues related to metabolic health – Obesity, diabetes, cardiovascular disease, high cholesterol • Gradual versus drastic changes to habits © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

Some Practical Dietary Tips to Consider Incorporating Carbohydrates – ↑ whole, unrefined

Fats – ↑ Unsaturated fats

• ↑Whole grains (>3 servings/day)

• ↑Nuts/Seeds, fish, olive oil, avocados

• ↓Unprocessed/refined carbs/foods

• ↓Fried foods

• ↓↓Sugary foods/drinks

• ↓Dairy/Cheese

Fiber (↑ >30 grams/day)

• Regular omega 3 fatty acids

• ↑ Fruits/Vegetables (>5-6 servings/day) • ↑Diversity of plant foods (>30 types/week) Protein - Plant >> Animal sources • ↑Beans/Tofu/Tempeh • ↓Red/processed meats Fermented Foods: ↑ ↑

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

• • • • • • • • • •

• Vitamin D (>30 ng/mL) Calorie counting/restriction are difficult to sustain long term Meal planning and preparation in advance Regular mealtimes not waiting until one is starving Ensure adequate hydration Learning to read ingredient lists and nutrition labels Gradual changes are more sustainable Making healthy swaps Make it a lifestyle and not a diet Frozen fruits/vegetable bags are healthy Doesn’t have to be raw salads. Cooked foods healthy too @UrviShahM D

57

Goals (Pick at least one to begin) • • • • • • • • • •

1 cup beans (plant protein) daily 2 cups fruit daily 1 serving fermented food daily 4 cups vegetables daily 1/3 cup nuts/seeds daily <6 teaspoons added sugars <2,300 mg salt >30 plant foods/week 1.5 cups whole grains daily >75% of your plate will be plant-based foods

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Canada’s revised food plate

@UrviShahM D

58

Food Labels

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

59

Diet and Kidney Disease (National Kidney Foundation)

https://www.kidney.org/atoz/content/plant-based © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

60

Traffic Light Approach to Foods (American College of Cardiology)

https://www.acc.org/Latest-in-Cardiology/Articles/2020/03/27/09/04/New-Insights-into-Heart-Healthy-Dietary-Habits © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

61

Surveys through the

Please Consider Participating in Dietary Survey Research Dietary Patterns Study Question: In patients with plasma cell disorders, are there significant differences in diet between groups?

Study Population: Plasma cell disorders Method: 30-minute survey Bonus: You will get a free nutrition report on completion

© 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

Supplement Use and Perceptions Study Question: Since being diagnosed, what changes have plasma cell disorder patients made to their supplement use habits of Vitamin D, Omega 3 Fatty acids, Turmeric/Curcumin and probiotics?

Study Population: Plasma cell disorders Method: 15-minute survey

@UrviShahM D

62

Conclusions Let's change our focus in multiple myeloma from Living Longer to

Living Better and Longer By incorporating lifestyle changes • Better Nutrition • Improved Fitness To reduce comorbidities and improve quality of life.

Shah UA et al. JAMA Oncology 2022 and Shah UA et al Leukemia 2023 © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

63

Future Directions Dietary Intervention and Observational Trials in • • • •

Newly diagnosed myeloma Myeloma on maintenance therapy Myeloma on various immunotherapies Similar trials in other cancers

Funding needed to do such studies © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

@UrviShahM D

64

Acknowledgements MSK Myeloma/BMT Faculty Fellows/Residents/Post docs Alexander Lesokhin, MD Richa Parekh, MD Marcel van den Brink, MD, PhD Ross Firestone, MD Saad Z Usmani, MD Ram Thirugnanasambandam, MD Sergio Giralt, MD Janine Joseph, MS (Moysich lab) Jonathan Peled, MD, PhD Collaborators Sham Mailankody, MD Neil Iyengar, MD (MSK) Jun Mao, MD (MSK) Neha Korde, MD Kinga Hosszu, PhD (SKI) Hani Hassoun, MD Justin Cross, PhD (SKI) Malin Hultcrantz, MD, PhD Michael Pollak, MD (McGill U) Carlyn Tan, MD Ola Landgren, MD, PhD (UofMiami) Gunjan Shah, MD Jens Hillengass, MD (Roswell Park) David Chung, MD Samir Parekh, MD (Mount Sinai) Oscar Lahoud, MD Emily Gallagher, MD (Mount Sinai) Heather Landau, MD Catherine Marinac, PhD (DFCI) Michael Scordo, MD Anita D’Souza, MD (U of Wisconsin) Kylee McLachlan, MD, PhD Susan Chimonas, PhD (MSK) Biostatistician Matteo Bellone, MD (Italy) Andriy Derkach, PhD Teng Fei, PhD Patients with plasma cell Research Dietitian disorders Francesca Castro, RD @UrviShahMD Research RN https://linktr.ee/urvishahmd Jenna Blaslov, RN Jena Wosleger, RN Research Associate Jeannen Santos Research Manager Laura Guttentag © 2023 Memorial Sloan Kettering Cancer Center, et al. All rights reserved.

The David Drelich, MD, CFP, Irrevocable Trust @UrviShahM D

65

We Want to Hear From You!

Feedback Survey At the close of the meeting a feedback survey will pop up.

This will also be emailed to you shortly after the workshop.

Please take a moment to complete this survey.

Webinar Video Replay & Slides

As follow up to todays webinar, we will have the speaker slides and a video replay available.

They will be provided shortly after the webinar concludes and posted to our website.

Thank You to Our Sponsors!