Patient & Family Webinar: The Future is Looking Bright for Myeloma Patients!

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Thank you to our sponsors!

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IMF Patient and Family Webinar

Agenda

*times listed in US Eastern Time Zone

10:00 – 10:10 AM 10:10 – 10:30 AM

Welcome Announcements with Susie Durie and Dr. Brian G.M. Durie Myeloma 101 Dr. Brian G.M. Durie

10:30 – 10:45 AM

Navigating the Journey: A Patient’s Perspective Maddie Hunter, Patient Advocate

10:45 – 11:00 AM

COVID-19: Vaccine and Variant Update Dr. Brian G.M. Durie

11:00 – 11:15 AM

Panel Discussion

11:15 – 11:25 AM

BREAK

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IMF Patient and Family Webinar

Agenda

*times listed in US Eastern Time Zone

11:25 – 11:45 AM

CAR T: Using Your Own Immune System to Fight Myeloma Dr. Thomas Martin, University of California San Francisco (UCSF)

11:45 – 12:05 PM

Treatment When Myeloma Comes Back Dr. Nikhil Munshi, Dana-Farber Cancer Institute

12:05 – 12:25 PM

Supportive Care Updates: COVID, CAR T & More Patricia Mangan, IMF Nurse Leadership Board

12:25 – 12:40 PM

Summary Panel Discussion

12:40 – 12:50 PM

Webinar Survey & Closing Remarks 3

IMF Patient and Family Webinar

Myeloma 101 Dr. Brian G.M. Durie Cedars-Sinai Outpatient Cancer Center

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Myeloma is treatable  Over 90% of patients respond to current therapies  Average first remission is 4 years or more  In 2021, average survival is at least 7-10 years  Some patients live over 15-20+ years  New therapies are constantly improving the outlook 5

Myeloma Expert Consultation Helps!  Good to do early!  Virtual consults more available.  Sets path for future  Guides local doctor

SEE: Questions to ask your doctor

https://www.myeloma.org/resource-library/tip-card-ask-your-doctor-these-important-questions

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IMF Patient and Family Webinar

Smoldering Myeloma

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New SMM Risk Score Tool* 2/20/20 Model FLC Ratio Serum M Protein Bone Marrow Plasma Cell %

20 2 g/dl 20%

Risk Factor

Coefficient

Odds Ratio (95% CI)

P-value

Score

0.69 0.96 1.56

1.99 (1.15, 3.45) 2.61 (1.36, 4.99) 4.73 (2.88, 7.77)

0.014 0.004 <0.0001

0 2 3 5

FLC Ratio 0-10 (reference) >10-25 >25-40 >40 M protein (g/dL) 0-1.5 (reference) >1.5-3 >3 BMPC% 0-15 (reference) >15-20 >20-30 >30-40 >40

0.95 1.30

2.59 (1.56, 4.31) 3.65 (2.02, 6.61)

0.0002 <0.0001

0 3 4

0.57 1.01 1.57 2.00

1.77 (1.03, 3.06) 2.74 (1.6, 4.68) 4.82 (2.5, 9.28) 7.42 (3.23, 17.02)

0.04 0.0002 <0.0001 <0.0001

0 2 3 5 6

FiSH abnormality

0.83

2.28 (1.53, 3.42)

<0.0001

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Risk Score

Low Risk High Risk

*689 of the original 2286 had complete data for all risk factors. Logistic regression analysis was performed.

Principal Investigators: Mateos; Kumar; San Miguel; Durie.

International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM) Blood Cancer J. 2020 Oct 16;10(10):102. doi: 10.1038/s41408-020-00366-3. https://www.nature.com/articles/s41408-020-00366-3

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When Should Treatment Be Initiated?

Potential New Myeloma or Smoldering Myeloma

Any Myeloma Defining Events?

•CRAB •≥60% PC •FLC ≥100 •MRI >1 focal lesion

Treat as Myeloma Rajkumar SV © 2020

No Myeloma Defining Events (SMM) High-Risk SMM (Median TTP ≈2 years)

Clinical Trials

Intermediate or Low-Risk SMM

Observation 9

What is recommended therapy for HR SMM? 

Observation for now?



Treatment to prevent progression (like Rd)?



Myeloma therapy: VRd or even Dara VRd



CURE type therapy: KRd + ASCT/ Dara KRd +/- ASCT 10

Careful testing required for diagnosis and monitoring  Bone marrow indicates % myeloma  X-rays/ scans show where lesions* are located X-ray image of myeloma lesions in arm

Myeloma cells as seen in a bone marrow aspirate

See further discussion: “What is a lesion?” https://www.myeloma.org/bone-disease

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IMWG diagnostic criteria for multiple myeloma (Myeloma Defining Events)

C

*CRAB Criteria

R A B

https://www.myeloma.org/resource-library/international-myeloma-working-group-consensus-criteria-response-minimal-residual

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More Test Details  Bone marrow FiSH shows chromosome results  MRI and PET/CT show more lesions than x-rays FISH

PET

MRI

F F

D D D

FiSH – Fluorescent in Situ Hybridization

F

D D

D

Colored spots show translocations: t(11;14)

F

PET F = Focal D = Diffuse

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Managing Myeloma: The Components Transplant Eligible Patients

Transplant Ineligible patients

Transplant

Maintenance

Initial Therapy Consolidation/ Maintenance/ Continued therapy

Supportive Care

https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25791

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Treatment Combinations: Now and Then NEW

VD Rev/Dex CyBorD VTD VRD KRD IRD Dara + triplet

SCT VD/VRD

Front line treatment

Induction

OLD

Thal/Dex VAD DEX

Consolidation

SCT

Thalidomide Bortezomib Lenalidomide Lenalidomide Carfilzomib Bortezomib Ixazomib Pomalidomide Ixazomib Daratumumab Daratumumab Isatuximab Pomalidomide Elotuzumab Panobinostat Bendamustine Selinexor Belantamab Mafodotin Melphalan Flufenamide (Melflufen)

Maintenance

Post consolidation

Nothing Prednisone Thalidomide

Relapsed

Rescue

Few options

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S0777 Trial: VRd vs Rd Eight 21-day Cycles of VRd

Randomization N = 525 Newly diagnosed MM

• •

Stratification: ISS (I, II, III) Intent to transplant @ progression (yes/no)

Bortezomib 1.3/mg2 IV Days 1, 4, 8, and 11 Lenalidomide 25 mg/day PO Days 1-14 Dexamethasone 20 mg/day PO Days 1, 2, 4, 5, 8, 9, 11, 12

Six 28-day Cycles of Rd Lenalidomide 25 mg/day PO Days 1-21 Dexamethasone 40 mg/day PO Days 1, 8, 15, 22

6 month of triplet followed by doublet Durie BGM, et al. ASH 2015

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S0777 Trial: VRd vs Rd

41 months

Durie et al. Blood Cancer Journal (2020) 10:53 https://www.nature.com/articles/s41408-020-0311-8

OS 80% = 4 years 55% = 7 years

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What to Expect with Treatment First “biochemical” relapse

100% Myeloma protein level

Deep first response 50%

MRD Undetected

Second response Later relapse from MRD undetected

Possible MRD undetected

5 years

10 years 18

Treatment Options

 “Triple therapy”: 3 drugs recommended • Most common = VRd* [Rd for older/frail] (Velcade®/ Revlimid®/ dexamethasone)  ASCT (Autologous Stem Cell Transplant)  Can be considered to achieve better response (after 3-6 months of VRd) Plus

Zometa®/ Aredia or denosumab for bone lesions

* Other options include VCd (CyBorD); KRd; Dara + Rd; Vd

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Treatment Options  Maintenance: used to sustain remission • Most common = Revlimid® ± Velcade®/ Ninlaro® Articles for Reference

(ixazomib)

Durie B, et al. Blood Cancer Journal 2020 May 11;10(5):53.

Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT) https://www.nature.com/articles/s41408-020-0311-8 Kumar S, et al. Leukemia. 2019; 33(7): 1736–1746.

Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance https://www.nature.com/articles/s41375-019-0384-1 Usmani S, et al. Blood Cancer Journal 2018 Nov 23;8(12):123.

Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma - an IMWG Research Project https://www.nature.com/articles/s41408-018-0155-7

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

Treatment Strategies in 2021 Triplets or quadruplets in frontline



Maintenance based upon risk



Decisive early relapse treatment (triplets if feasible)



Earlier use of new immune therapies 21

Caregivers Need Care Too!

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IMF Website – http://www.myeloma.org http://www.myeloma.org

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IMF Patient and Family Webinar

Navigating the Journey: A Patient's Perspective Maddie Hunter Patient Advocate

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How could this be true?

What is my prognosis?

How do I decide my best treatment?

Will I ever be able to understand and say the names of all the medications?

How will I feel on treatment?

Should I get a second opinion?

How will I be able to take care of my son?

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EARTH

WATER

AIR

FIRE 28

EARTH What do I need to do to feel more grounded and more in control?

Develop a good relationship with a myeloma specialist Keep learning about myeloma Join a support group

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WATER What nourishment do I need now?

Water Movement Support Beliefs

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AIR What do I need to breathe in?

What do I need to exhale?

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FIRE What sparks me and makes me feel alive?

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Navigating our myeloma journey is about building our awareness of what we need.

Reflecting on the right questions can help us live the best life we can with myeloma.

Thank you.

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IMF Patient and Family Webinar

COVID-19: Vaccine and Variant Update Dr. Brian G.M. Durie Cedars-Sinai Outpatient Cancer Center

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IMF 2nd Quarter Support Group Leader Virtual Meeting

Data from the CDC and WHO. The data includes cases as of April 25, 2021. https://covid.cdc.gov/covid-data-tracker/#global-counts-rates and https://covid19.who.int/

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IMF 2nd Quarter Support Group Leader Virtual Meeting

Overall US COVID-19 Vaccine | Deliveries and Administration; Maps, charts, and data provided by CDC https://covid.cdc.gov/covid-data-tracker/#vaccinations and https://covid.cdc.gov/covid-data-tracker/#datatracker-home

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Vaccination for Myeloma Patients  YES!!!  Impact of ongoing treatment unclear  Use common sense  Antibody responses suboptimal 37

Vaccination for Myeloma Patients  Checking levels = OK! (if feasible at ~2-3 weeks post 2nd dose) rd  3 (booster) dose being discussed (against B117 and other variants)  Anticipate separate guidance for immune compromised as for flu, etc.

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Which vaccine?  Pfizer/ Moderna – Excellent!  J&J – not live!/ single shot only  Blood clot risk  AstraZeneca – 79%76% efficacy (slightly reduced)  Blood clot risk

100% reduction of hospitalizations and deaths

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Masks – still required! Airborne transmission dominant Variants a serious challenge Beware asymptomatic spread Watch out for young people! Still avoid travel Indoor space a severe problem 40

Masks – still required! So: use best masks possible – N95 or double (nose and mouth) Consider googles/ glasses – if risk situation Remember: antibody levels may be low post vaccination CDC: Your Guide to Masks https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/about-face-coverings.html

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CDC: When You’ve Been Fully Vaccinated - How to Protect Yourself and Others https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html

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Patient Guidance

Question: Can I go for a walk?

• Yes

Question: Can I go to the dentist?

• Yes, with care

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Things to Think About

 Location and who may have been in that space prior to their members  Local guidance -- are masks mandatory or recommended?  Ventilation  Spacing: is there ample space for members to be safely distanced 44

     

Common Issues Pandemic fatigue/ stress Not feeling resilient Healthcare team not coordinated Not prepared for Zoom or appointments Need electronic help!

Contacts with unknown COVID-19 status 45

Pandemic Fatigue

 Real for everyone!  Important to reach out to family and friends  Try to de-stress  Shedd Aquarium – Penguins  Work on resilience  Living Well with Myeloma: Building Your Resilience During Challenging Times (IMF video)  Resilience Builder Tool (link on IMF website)

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What Can You Do Once You’re Vaccinated?

New York Times – March 30, 2021 https://www.nytimes.com/interactive/2021/03/30/opinion/coronavirus-vaccine-risks.html

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What does the future hold?

 “Herd immunity” ( ≥ 70% immune) th  A 4 wave due to variants  A need for “booster” vaccination

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Support Group Virtual GoToMeetings

Over 90 support groups are now holding monthly virtual GoToMeetings through the IMF

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Support Group Virtual GoToMeetings

Over 90 support groups are now holding monthly virtual GoToMeetings through the IMF

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We will get through this together!

Myeloma has no borders

“Do Remember They Can’t Cancel the Spring” – David Hockney

Support messages in the sky above Los Angeles An apricot tree grows in Turkey

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IMF Patient and Family Webinar Type your questions to the panel and press Submit.

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IMF Patient and Family Webinar

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IMF Patient and Family Webinar

CAR T: Using Your Own Immune System to Fight Myeloma Dr. Thomas Martin

UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, CA

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Immunotherapy in MM CAR T Cells: A Review Thomas G. Martin, MD Clinical Professor of Medicine Interim Chief, Division of Hematology Co-Director, Myeloma Program University of California, San Francisco San Francisco, California

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Natural History of Multiple Myeloma Symptomatic

Asymptomatic

M Protein (g/L)

100

2. RELAPSE

ACTIVE MYELOMA 1. RELAPSE

50

20

REFRACTORY RELAPSE

MGUS or smoldering myeloma

Plateau remission

First-line therapy

Second-line therapy

Third-line therapy

CAR T-cells 56

Myeloma Therapeutics Over Time

2002.

2012

2022

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Immunotherapy in Cancer: Changing the Way Our Immune System Works Army

Navy

Marines

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Immunotherapy Updates: Products in Trials Competitive landscape for Triple Class refractory

IMiDs / CelMODs/ Novel Drugs

Monoclonal Antibodies (CD38)

BCMA ADCs

BCMA Bispecifics

CC-220 (Iberdomide), CC-94480

SAR442085 Hexabody-CD38 TAK-079

Belantamab Mafodotin dreaMM3,4,5,6,7,8

Teclistamab AMG-701(420) CC-93269

Venetoclax

TAK-573 AMG-424 GBR-1343

MEDI2228 CC-99712

TNB-3838, PF-06863135, REGN5458,

Immune – Toxin AK-169

Non-BCMA STRO-01 FOR46

Melflufen

Non-BCMA GO39775 JNJ-64407564

Cellular therapies BCMA CARs Idecabtagene vicleucel (bb2121), bb21217 JCARH125 Ciltacabtageneautoleucel/JNJ-4528 (CARTITUDE-1) P-BCMA-101 CT053 Many others Penn/NIH/Seattle 59

Types of Monoclonal Antibodies Naked Antibodies

Bispecific Antibodies

• Nothing is attached SLAMF7 CD38

Antibody Drugconjugates • A toxin or radioactive isotope is attached 60

T-Cell Therapy for Cancer

CAR Features MM

Cell targets Binding domain Transmembrane domain

Signaling Domain -4-1BB, CD28 -CD3z

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Immunotherapy for MM - Targets and Therapeutics • BCMA Therapeutics

• Current MM Targets • BCMA • TACI • • • • • • • • •

GPRC5D FcRH5 CD138 CD38 CD19 SLAMF7 ASCT2 CD229 Kappa light chain

• CARs

• Idecabtagene vicleucel • Ciltacabtagene autoleucel

BCMA

• ADCs

• Belantamab mafodotin • MEDI2228

• Bispecific antibodies T-cell

• Teclistamab • ~6 others at ASH2020

Cho SF et al. Front Immunol 2018; 9:1821

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CAR T Cell Process 1. Apheresis – T cell collection 1. Autologous (self) 2. Allogeneic (Donor) 2. Manufacturing (3-5 weeks) 1. Expand the # of cells 2. Insert the CAR DNA 3. Bridging chemotherapy 4. LD Chemotherapy 1. 3 days of chemo 5. T cell infusion (inpatient) 6. Watch for side effects 1. CRS 2. Neurologic toxicity

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CAR T cell Toxicity 1. CRS (>80% of patients; <10% Gr3-4) 1.

2.

3.

Occurs between 1 hour and 10 days after infusion Lasts between 3-5 days Symptoms: 1.

2.

3.

4.

Fever, chills, HA, fatigue and malaise [flu-like] Low blood pressure, fast heart rate Shortness of breath, need for oxygen,

Treatment: tocilizumab +/- dexamethasone

2. Neurotoxicity (<30%; <10% G3-4) 1.

2.

3.

Occurs between 2 days to ~30 days, some later Lasts between 3-14 days, few have longer symptoms Symptoms 1.

2.

3.

Confusion, delirium, aphasia Tremor, Parkinson-like symptoms, nerve palsies Brain swelling is rare

3. Cytopenias 1.

2.

3.

Low WBC Low platelets Anemia

4. Infection 1.

Viral, Bacterial, fungal and unusual infections

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Chimeric Antigen Receptor (CAR) Therapy for Multiple Myeloma MM Targets • CD19 • BCMA • SLAMF7

CD19 BCMA

CAR T: A Game Changer in MM?

Gene Transfer Vectorss • γ-Retrovirus • Lentivirus • Transposon Extracellular Domain • scFv • Centyrin Signaling Domain • CD3ζ + • CD28 or 4-1BB

Kochenderfer et al. 2016 66

BCMA-Directed CAR T-cell Therapeutics Vector Co-Stim Domain

KarMMa; Ph 2 Ide-cel: bb2121

CARTITUDE-1, Ph 1 Cilta-cel: JNJ-4528

EVOLVE; Ph1-2 Orva-cel, JCARH125

Poseida

Lentiviral

Lentiviral

Lentiviral

Transposon

CD3ζ/41BB

CD3ζ/41BB

CD3ζ/41BB

CD3ζ/41BB

Human - scFv

Centyrin

Binding Domain

Murine - scFv

Llama – dual VHH

# Patients// #prior Lines

54 // 6

29 // 5

44 // 7

23//6

Cell dose (CD3)

450 x 10e6

~50-100 x 10e6

50-450 x 10e6

51-857 x10e6

ORR

82%

100%

82%

63%

PFS

12.1

NR

NR

NR

CRS Gr 1-4

84% (6% ≥Gr 3)

86% (3% Gr3)

80% (9% Gr 3)

9.5% (all Gr 1-2)

Neurotox Gr 1-4

18% (3% Gr3)

10% (3% Gr3)

25% (7% Gr 3)

4.8% (4.8% Gr 3)

Munshi et al. ASCO 2020, Madduri et al. ASH 2019, Mailankody et al. ASH 2018, Patel et al. ASH 2019 Tom Martin

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Ph 2 - KarMMa-1: Study Design

bb2121 CAR Design MND SP Anti-BCMA scFv Promot er

Tumor binding domain

CD8 Linke r

4-1BB

CD3z

Signaling Domains

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KarMMa-1 Demographics Characteristics Age, median (range), y Male, % ECOG PS, % R-ISS Stage,* %

0 1 2 I II III

High-risk cytogenetics [del(17p), t(4;14), t(14;16)],† %

Ide-Cel−Treated (N=128) 61 (33−78) 59 45 53 2 11 70 16 35

High tumor burden (≥50% BMPCs), %

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Tumor BCMA expression (≥50% BCMA+),‡ %

85

Extramedullary disease, %

39

Time since initial diagnosis, median (range), y

6 (1−18)

No. of prior anti-myeloma regimens, median (range)

6 (3−16) 94 34 84 26 88

Prior autologous SCT, % Refractory status, % Any bridging therapies for MM, %

1 >1 TriplePenta-

• Patients were heavily pretreated, refractory to last line per IMWG criteria, and mostly refractory to all 3 major MM drug classes • The majority had high tumor burden and more than one third had extramedullary disease and high-risk cytogenetics • Tumor BCMA expression identified by IHC in all patients • Most patients (88%) received bridging therapy during CAR T cell manufacturing –

Only 5% of patients responded (5 PR, 1 VGPR) to bridging therapy Munshi N et al ASCO 2020. Abstr 8503.

Munshi NC et al. N Engl J Med 2021;384:705-716.

Data cutoff: 14 Jan 2020. Ab, antibody; BCMA, B-cell maturation antigen; BMPC, bone marrow plasma cells; ECOG PS, Eastern Cooperative Oncology Group performance status; IMWG, International Myeloma Working Group; MM, multiple myeloma; PR, partial response; R-ISS, revised International Staging System; SCT, stem cell transplant; VGPR, very good PR. *R-ISS stage was assessed at enrollment; unknown for 3 patients. †Baseline cytogenetics not evaluable/missing for 17 patients; 45 patients (35%) had 1q amp abnormality. ‡No minimum tumor BCMA expression required for study entry.

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Munshi N et al ASCO 2020. Abstr 8503.

Munshi NC et al. N Engl J Med 2021;384:705-716.

KarMMa-1 Clinical Response 100

Response, %

80

CR/sCR and MRD-negative CR/sCR and MRD not evaluable* VGPR ORR=69% PR 24

60

ORR=50% 40

20

25

25

CRR 25%

4 14

ORR=82% ORR=73%

28

CRR 29%

CRR 39% 11 26

26 17

26

CRR 33% 7 20

21

0

CAR+ T cells:

150 × 10⁶ (n=4)

300 × 10⁶ (n=70)

450 × 10⁶ (n=54)

Ide-cel treated (N=128)

• Primary (ORR >50%) and key secondary (CRR >10%) endpoints met in the ide-cel−treated population − ORR 73% (95% CI, 65.8−81.1; P<0.0001*) − CRR (CR/sCR) 33% (95% CI, 24.7−40.9; P<0.0001)

• Median time to first response of 1.0 mo (range, 0.5−8.8); median time to CR of 2.8 mo (range, 1.0−11.8) • Median follow-up of 13.3 mo across target dose levels Data cutoff: 14 Jan 2020. MRD-negative defined as <10-5 nucleated cells by next generation sequencing. Only MRD values within 3 mo of achieving CR/sCR until progression/death (exclusive) were considered. Values may not add up due to rounding.

CR/sCR, complete response/stringent CR; CRR, CR rate; MRD, minimal residual disease; ORR, overall response rate (≥PR); PR, partial response; VGPR, very good PR. *P value at the primary data cutoff with same ORR and 95% CI. *Of 42 total patients with ≥CR, 8 were not evaluable for MRD and 1 had values outside the 3-mo window prior to CR/sCR.

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KarMMa-1 Progression-Free Survival PFS by Target Dose

• PFS increased with higher target dose • median PFS was 12 mo at 450 × 106 CAR+ T cells

PFS by Best Response

• PFS increased by depth of response • median PFS was 20 mo in patients with CR/sCR Munshi NC et al. N Engl J Med 2021;384:705-716.

Data cutoff: 14 Jan 2020. NE, not estimable; PFS, progression-free survival.

CARTITUDE-1: Phase 1b/2 Study Design Primary objectives

 Phase 1b: Characterize the safety of cilta-cel and confirm the 

recommended phase 2 dose (n=29) Phase 2: Evaluate the efficacy of cilta-cel by ORR (n=68)

Key eligibility criteria

    

Progressive MM per IMWG criteria ECOG PS ≤1 Measurable disease ≥3 prior therapies or double refractory Prior PI, IMiD, anti-CD38 therapy

Screening (28 days) Apheresis Bridging therapya (as needed) Cy (300 mg/m2) + Flu (30 mg/m2) Cilta-cel infusion Target: 0.75x106 (0.5–1.0x106) CAR+ viable T cells/kg

Day -5 to -3 Day 1

Post-infusion assessments Safety, efficacy, PK, PD, biomarker

 Median administered dose: 0.71x106 (0.51–0.95x106) CAR+ viable T cells/kg

Follow-up

CAR, chimeric antigen receptor; Cy, cyclophosphamide; ECOG PS, Eastern Cooperative Oncology Group performance status; Flu, fludarabine; IMiD, immunomodulatory drug; IMWG, International Myeloma Working Group; MM, multiple myeloma; ORR, overall response rate; PD, pharmacodynamics; PI, proteasome inhibitor; PK, pharmacokinetics. aTreatment with previously used agent resulting in at least stable disease.

72 ClinicalTrials.gov number, NCT03548207; 01 Sept 2020 data cut-off.

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CARTITUDE-1: Phase 1b/2 Study Design Primary objectives

 Phase 1b: Characterize the safety of cilta-cel and confirm the 

recommended phase 2 dose (n=29) Phase 2: Evaluate the efficacy of cilta-cel by ORR (n=68)

Key eligibility criteria

    

Progressive MM per IMWG criteria ECOG PS ≤1 Measurable disease ≥3 prior therapies or double refractory Prior PI, IMiD, anti-CD38 therapy

Screening (28 days) Apheresis Bridging therapya (as needed) Cy (300 mg/m2) + Flu (30 mg/m2) Cilta-cel infusion Target: 0.75x106 (0.5–1.0x106) CAR+ viable T cells/kg

Day -5 to -3 Day 1

Post-infusion assessments Safety, efficacy, PK, PD, biomarker

 Median administered dose: 0.71x106 (0.51–0.95x106) CAR+ viable T cells/kg

Follow-up

CAR, chimeric antigen receptor; Cy, cyclophosphamide; ECOG PS, Eastern Cooperative Oncology Group performance status; Flu, fludarabine; IMiD, immunomodulatory drug; IMWG, International Myeloma Working Group; MM, multiple myeloma; ORR, overall response rate; PD, pharmacodynamics; PI, proteasome inhibitor; PK, pharmacokinetics.

73 aTreatment with previously used agent resulting in at least stable disease.

ClinicalTrials.gov number, NCT03548207; 01 Sept 2020 data cut-off.

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CARTITUDE-1: ORR and MRD Assessment 100%

ORRa: 96.9% (94/97)

Patients

80% 60%

sCR: 67.0%

67.0%

≥VGPR: 92.8%

N

Frequency in evaluable patients n=57c

Frequency in all treated n=97d

Overall MRD-

53

93.0%

54.6%

MRD- and sCR

33

57.9%

34.0%

MRD- and ≥VGPR

49

86.0%

50.5%

 Median time to first response: 1 month (0.9–8.5)

40%

 Responses ongoing in 70 (72.2%) patients 20%

 Of evaluable patients, 93.0% achieved MRD 10-5 negativity

25.8%

0% Best responseb =

̶

4.1%

sCR

VGPR

PR

Median time to MRD 10-5 negativity: 1 month (0.8–7.7)

 Among patients with 6 months individual follow-up, most had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood

CAR, chimeric antigen receptor; CR, complete response; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aPR or better, Independent Review Committee assessed. bNo patient had CR or stable disease as best response. cMRD was assessed in evaluable samples at 10-5 threshold by next-generation sequencing (clonoSEQ, Adaptive Biotechnologies) in all treated patients at Day 28, and at 6, 12, 18, and 24 months regardless of the status of disease measured in blood or urine; patients were not evaluable primarily due to lack of an 74 identifiable clone in the baseline bone marrow sample. dAll treated patients.

74

CARTITUDE-1: PFS Overall PFS

PFS by sCR and VGPR

12-month PFS sCR: 84.5% (95% CI, 72.0–91.8) VGPR: 68.0% (95% CI, 46.1–82.5) Median PFS not reached in either group

Overall 12-month PFS: 76.6% (95% CI, 66.0–84.3) Median PFS not reached

No. at risk sCR 65

65

62

53

27

12

2

1

1

0

VGPR 25

24

19

15

3

2

0

0

0

0

At median duration of follow-up of 12.4 months (range, 1.5–24.9), median PFS has not been reached 12-month PFS rate: 76.6% (95% CI, 66.0–84.3) 12-month OS rate: 88.5% (95% CI, 80.2–93.5) OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.

75

Patients with triple class refractory MM - The unmet need with poor prognosis • MAMMOTH Study • Retrospective review of RRMM • 275 patients • PI, IMiD and CD38 exposed • Median OS was <9 months in MAMMOTH in patients with disease refractory to anti-CD38 mAbs1

Median OS in MAMMOTH study from T01 mOS (95% CI), months All: 8.6 (7.2–9.9) Not triple-refractory: 11.2 (5.4–17.1) Triple- and quad-refractory: 9.2 (7.1–11.2) Penta-refractory: 5.6 (3.5–7.8)

Cilta-cel: What if?

• Median OS was <6 months if penta-refractory • Current treatment options include conventional chemotherapy, salvage ASCT, recycling previous regimens, selinexor + dexamethasone, belantamab mafodotin and clinical trials2

1. Gandhi UH, et al. Leukemia. 2019;33(9):2266-2275.

76

76

CAR T-cell in MM: How do We Improve?

• What about Innovation with CARs? 1. Improved CARs

- Faster Manufacturing or Off-the-shelf (<7 days) - Better T cells – Tscm/cm - Persistence: a good “second wave”

2. Improved patient selection - Early relapse (1-3 PLT) - Frontline: replace ASCT? - Lower burden of disease

3. Additional targets and combinations - GPRC5D +/- BCMA (dual targets) - CD19 + BCMA - CAR + BISPECIFIC, CAR + CelMOD

4. Better understand mechanisms for resistance - Antigen loss - Quiescent Myeloma cells, “stem cell”

77

Prediction: Future Strategies in MM (2025-2030) Where and in what combination will immunotherapy have the most Impact?

Newly Diagnosed MYELOMA Symptomatic

SMM Bispecific - Sequence TCE - MRD x 6-12m - STOP

M Protein (g/L)

100

MM

50

SMM

Plateau remission

EARLY RELAPSE

Front-line therapy

2.

RELAPSE

Induction

REFRACTORY RELAPSE

1.

RELAPSE

--- QUAD (mAb) Consolidation

20

--- CAR vs. Bispecific

2nd-line therapy

Maintenance

3rd-line therapy

Frontline QUAD: + CAR vs. transplant

Early Relapse (1-3 Prior Lines) Late Relapse Novel CAR (Different Ag) ALLO CAR T QUAD + autoSCT then Novel Ab: ADC-combo vs. Bi-/Trivalent TCE Third party cellular therapy (NK + Macro) MRD (+): Consolidation: CAR (TE) vs. Bispecific (TI) Bi-/Tri TCE combinations MRD (-): Maintenance: Len/mAb vs. Bispecific Tom Martin

78

Future: ND Myeloma treatment paradigm Triplet Induction

(4-6 cycles) Triplet Induction (4-6 cycles)

CAR T-cell (1x 4wk)

+/- Maintenance (1, 2, 3 yr) STOP THERAPY!

CAR T-cell (1x 4wk)

Induction followed by continuous therapy (8-12 cycles or more?)

Relapse

SCT ineligible

SCT eligible

32,000/yr 12,000/yr 4,000/yr 16,000/yr

CAR Tumor Burden

VGPR

CR MRD 79

Future Therapeutics • UCSF Homegrown CARs - Lentigen – BCMA vector • Clinical Protocol – Phase 1 • UCSF to holds IND • Cross reference with Prodigy and Lentigen data

80

Conclusions: So where will CARs fit best……..?

• Responses in RRMM are amazing • Will we have long-term remissions?

• CARs vs auto, CARs vs. Bispecifics vs BCMA-ADC

• Which surface target will be best … BCMA???

• Resistance mechanism will be important • Loss of BCMA reported but uncommon

• Cowan et al. ASH 2019 : BCMA CAR T + GSI • 3 Prior BCMA (2 CAR, 1 Bispecific) • 10 patients => 100% ORR

• What clinical factors we be most important?

• • • •

Convenience [one and done] Least toxic [No hospitalization, least consultants] Most effective [deep and durable, tmt-free interval] Goal to STOP therapy (and avoid Dex) Tom Martin

81

IMF Patient and Family Webinar

Treatment When Myeloma Comes Back Dr. Nikhil Munshi Dana-Farber Cancer Institute Boston, MA

82

Relapse Treatment options in Multiple Myeloma Nikhil C. Munshi, MD Professor of Medicine Harvard Medical School Kraft Family Chair Director, Basic and Correlative Science Jerome Lipper Myeloma Center Dana-Farber Cancer Institute Boston VA Healthcare System

Definitions • Relapsed myeloma: Disease that is recurring after a response to the most recent therapy • Refractory myeloma: Disease that is progressing despite ongoing therapy

How Do We Decide Next Treatment?

Factors Influencing the Treatment Decision-making at the Relapse Setting Frailty

Disease morbidity

Risk assessment

Age

Refractory disease

ISS

Performance status

Renal impairment

Cyto-genetics

Disability

Bone disease

Co-morbidities

Treatment history Previous therapies

Lifestyle

Patient preference Travel / infusion time

The most effective regimen, safe and maintaining QoL

• Choice of PI- or IMiD-based partner depends on prior treatment • Nearly all phase 3 studies show triplets perform better than doublets • Cross trial comparisons should not be done as Clegg A et al. Lancet 2013;381:752–762; Handforth C et al. Ann Oncol 2015;26:1091–1101; Chen X et al. Clin Interv Aging 2014;9:433–441; Palumbo A et al. Blood 2015;125:2068–2074; Jhaveri D et al. Haematologica 2016;101:1–881 (Abstract E1312); Sonneveld P et al. Leukemia 2013;27:1959–1969; Faiman BM et al. Clin J Oncol Nurs 2011;15:66–76; Miceli TS et al. Clin J Oncol Nurs 2011;15:9–23; Greipp PR et al. J Clin Oncol 2005;23:3412–3420; Binder M et al. Haematologica 2016;101:P665; Merz M et al. Haematologica 2016;101:P650; Chng WJ et al. Leukemia 2016;30:1071–1078; Chung TH et al. PLoS One 2013;20:e66361; Sonneveld P et al. Leukemia 2013;27:1959–1969; Ramsenthaler C et al. BMC Cancer 2016;16:427; Williams LA et al. J Clin Oncol 2016;34:e18127; Ramasamy K et al. Haematologica 2017;102:E1457.

Therapeutic Advances in Multiple Meyloma 14

• 11 new Agents in last 15 years: •

Proteasome inhibitors: bortezomib, Carfilzomib, Ixazomib

•

Immunomodulator: thalidomide, lenalidomide, pomalidomide

•

HDAC inhibitor: Panobinostat

•

Monoclonal antibodies: elotuzumab, daratumumab Isatuximab,

•

Exportin inhibitor: Selinexor

•

Alkylating Agent: bendamustine, Melflufan

•

Existing older agents: melphalan, dexamethasone. cyclophosphamide, anthracycline, etoposide

•

Cell therapy: Ide-cel

•

Near approval: Cilta-cel, venetoclax, BCMA-bispecifics

Blentamab

• 2-, 3-, 4-drug combinations - effective in relapsed/refractory MM • 28 FDA approvals and median patient survival prolonged 3-4 fold, from 3 to at least 8-10 years, and MM is a chronic illness In many patients.

Therapy for Relapsed MM:Triplets Preferred With Second Generation IMiDs, PIs, MoAbs Active In Len and Bort refractory MM • Carfilzomib Pom Dex (no neuropathy) • Dara Pom Dex ; Dara Carfilzomib Dex (deep responses, FDA approved) • Elo Pom Dex (well tolerated, FDA approved) • Isatuximab Pom Dex (FDA approved) Active in Bort refractory MM • Elotuzumab Len/Dex (indolent relapse), Ixazomib Len • Dex (all oral), Carfilzomib Len Dex (no neuropathy), Dara Len dex (MRDresponses) (all FDA approved) Active in Len refractory MM • Pom Bort Dex, Dara Bort Dex (MRD- responses)(FDA approved)

Therapy for Relapsed MM:Triplets Preferred With Second Generation IMiDs, PIs, MoAbs Active in Len and Bort refractory MM - (Combining older drugs) • Cytoxan – VCD, KCD • Melphalan (MPV) • Bemdamustine (Bend VD; Benda KD)

Active in Len, Pom, Bort, Carfil, Dara refractory MM - (side effects)(FDA approved) • Selinexor • Belantomab mafodotin • Melflufan • Abecma

Management of Patients at First Relapse Relapsing After Lenalidomide based Treatments Bortezomib-Dexamethasone Combinations First relapse after IMiD-based induction1 Doublets Kd / Vd

Pomalidomide PVd vs Vd 559

N Efficacy

Tx

Median f/p, mos

Control

Triplets based on Bortezomib DaraVD or PanoVD or EloVD or VCD

Daratumumab*

Carfilzomib

Selinexor

Venetoclax

Kd vs Vd 929

SVD vs Vd 195 vs 207

VenVD vs VD 194 vs 97

DVd vs Vd 498 Tx

16

Control

Tx

Control

Tx

37.5

26.9

Control

Tx

16.5

Control 18.7

ORR

82%

50%

85%

63%

76%

63%

76%

62%

82%

68%

CR

16%

4%

30%

10%

13%

6%

17%

11%

13%

1%

Median PFS, mos

11

7

16.7

7.1

18.7

9.4

13.9

9.46

22.4

11.5

NR

NR

NR

47.6

40.0

NR

25

NR

25

– MedianOS, mos

NR

Richardson et al. Lancet Oncol 2019; 20: 781–94; Palumbo A et al. N Engl J Med. 2016;375:754; Spencer A et al. Haematologica. 2018; Sep 20 [epub ahead of print]; Dimopoulos MA et al. Lancet Oncol.

2016;17:27; Dimopoulos et al ASCO 2020; Kumar S. EHA 2019.

Management of Patients at First Relapse in Patients Relapsing After Bortezomib based Treatments Lenalidomide-Dexamethasone Combinations First relapse after Bortezomib-based induction1 Doublets Rd

N Efficacy

Ixazomib

Elotuzumab

Carfilzomib*

Daratumumab

IRd vs Rd 722

ERd vs Rd 646

KRd vs Rd 792

DRd vs Rd 569

IRD

RD 23

Median f/u, mos ORR

78.3%

CR Median PFS, mos

Triplets based on Rd DaraRd or KRd or IxaRd or EloRd

EloRD RD

KRD

Min 48 mos 71.5%

RD

DRD

67

32.9

79%

66%

87%

66.7%

93%

76%

12%

7%

5%

9%

32%

9.3%

55%

23%

21

14.7

19

14.9

26

16.6

NR

17.5

– Median OS, mos

RD

NR

NR

48.3

39.6

– 48.3

40.4

–

Moreau P et al. N Engl J Med. 2016;374:1621; Dimopoulos MA et al. Br J Haematol. 2017;178:896.

Stewart AK et al. N Engl J Med. 2015;372:142; Stewart AK et al. Blood. 2017;130: Abstract 743.

Dimopoulos M et al. J Hematol Oncol. 2018;11:49; Dimopoulos MA et al. N Engl J Med. 2016;375:1319.

NR

NR

What is the Goal of Traetment in Relapsed Disease?

• Obtain the maximal response

92

POLLUX and CASTOR POLLUX R A N D O M I Z A T I O N

DRd (n = 286)

D 16 mg/kg IV Hebdomadaire: Cycles 1-2 Toutes les 2 semaines: Cycles 3-6 Toutes les 4 semaines jusqu’à progression R 25 mg PO (identique à Rd seul) d 40 mg

Rd (n = 283)

R 25 mg PO Jours 1-21 de chaque cycle jusqu’à progression d 40 mg weekly until PD

Evaluation de la MRD

 Lors de la suspicion de CR  À 3 et 6 mois après CR

CASTOR R A N D O M I S A T I O N

DVd (n = 251)

D 16 mg/kg IV Hebdomadaire : Cycles 1-3 Toutes les 3 semaines : Cycles 4-8 Toutes les 4 semaines : Cycles 9+ V 1.3 mg/m2 SC (identique à Vd seul) d 20 mg

mg/m2

Vd (n = 247)

V 1.3 SC aux jours 1, 4, 8, et11 pour 8 cycles d 20 mg aux jours 1, 2, 4, 5, 8, 9, 11, et 12 pour 8 cycles

Evaluation de la MRD

 Lors de la suspicion de CR  A 6 et 12 mois après la 1ère dose

CASTOR & POLLUX: Proportion of patients with MRD negativity at 10–4, 10–5, and 10–6 POLLUX

CASTOR

Daratumumab in combination with standard of care significantly improved MRD-negative rates at all thresholds *** P <0.0001. ** P <0.005. * P <0.05.

P values calculated using likelihood-ratio chi-square test.

Avet-Loiseau H, et al. Presented at ASH 2016 (Abstract 246), oral presentation.

CASTOR & POLLUX: PFS According to MRD Status at 10–5 POLLUX

• • •

CASTOR

Lower risk of progression in MRD-negative patients More patients achieve MRD negativity when adding daratumumab PFS benefit in MRD-positive patients who received daratumumab-containing regimens versus standard of care Avet-Loiseau H, et al. Presented at ASH 2016 (Abstract 246), oral presentation.

Patients with Relapsed Myeloma May Have Similar Survival as Newly-diagnosed if They Receive MRD negativity

Munshi N et al., Blood Adv. 2020

Immune-therapies under investigation in Hematological Malignancies Immunotherapy1,2

Active

Passive

(Designed to act on the immune system itself)

I-O therapies •

Immune effector cell modulators • Checkpoint Inhibitors • Co-stimulatory agonists

Therapeutic cancer vaccines •

•

•

(Designed to act on the tumor)

Antitumor mAbs

Unspecific

Cell-based DC-based cancer vaccines

•

Single antigen/ peptide-based

•

• •

Cytokines Interleukins Interferons

•

Tumordirected mAbs

IMiDs

•

Ab-drug Conjugates (ADC)

Adoptive

•

Cell therapies • Adoptive T-cell therapy

DC, dendritic cell; IMiD, immunomodulatory agent; I-O, immuno-oncology; mAb, monoclonal antibody.

1. Finn OJ. Ann Oncol. 2012;23(suppl 8 ):viii6-viii9. 2. Mellman I et al. Nature. 2011;480:480-489.

CAR T-Cell Therapy in Multiple Myeloma - Outcome Ide-cel Ph1 N=128

Cilta-cel Ph1b/2 N=97

Orva-cel Ph1b/2 N=62

bb21217 Ph1 N=69

P-BCMA-101 Ph1/2 N=55

RESPONSE ORR

73%

96.9%

92%

68%

44% - 75%b

CR

33%

67%

36%

29%

NR

5.8 mo

120-508 daysb

SURVIVAL Median follow-up

13.3 mo

12.4 mo

Median DOR

10.7 mo

Not reported

Not reported

17.0 mo

Not reported

Median PFS

8.8 mo

12 mo PFS: 76.6%

Not reported

Not reported

Not reported

Median OS

19.4 mo

12 mo OS: 88.5%

Not reported

Not reported

Not reported

70% (4%)

17% (0%)

16% (4%)

4% (4%)

CYTOKINE RELEASE SYNDROME All grades (≥3 ) %

76% (7%)

95% (4%)

89% (3%)

NEUROTOXICITY All grades (≥3 ) %

36% (2%)

21% (10%)

13% (3%)

Munshi et al; Madduri et al; Lin et al; Alsina et al; Kumar et al; Costello et al; Jiang et al; Mailankody et al; ASH/ASCO 2020

Bispecific T Cell Engagers (Bites) in Multiple Myeloma Tesclistamab Ph1 N=149

AMG-701 Ph1 N=85

REGN5458 Ph1 N=49

PF-3135 Ph1 N=30

Talquetamab Ph1 N=157

Cevostamab Ph1 N=53

BCMA-CD3

BCMA-CD3

BCMA-CD3

BCMA-CD3

GPRC5D-CD3

FcRH5-CD3

Q2WQW IV or SC IV: 0.3-19.2 µg/kg SC: 80-3000 µg/kg

QW IV (0.005-18 mg)

QWQ2W IV (3-96mg)

QW SC (80-1000µg/kg)

QW or Q2W IV: 0.5-180 µg/kg SC: 5-800 µg/kg

Q3W IV (0.05-160mg)

CRS, % Any grade Grade ≥3

55% 0

65% 9%

39% 0

73% 0%

54% 3%

76% 2%

NT, % Any grade Grade ≥3

5% 1%

Not reported

12% 0

Not reported

6% 2%

Not reported

ORR

At RP2D (1500 µg/kg SC): 73% (≥CR, 23%)

26% (≥CR, 10%)

39% (≥CR, 16%)

80%

At RP2D (405 µg/kg SC): 69% (≥CR, 15%)

In ≥20 mg cohorts: 53% (≥CR, 18%)

Median follow-up

At RP2D: 3.9 mo

6.5 mo

2.6 mo

Not reported

≥60 µg/kg: 7.4 mo ≥405 µg/kg: 3.7 mo

8.1 mo

Median DOR

Not reached

Not reached

6.0 mo

Not reported

Not reached

8 patients ≥6 mo

Median OS

Not reached

Not reported

Not reported

Not reported

Non reported

Not reported

Target Dosing Schedule

Garfall et al; Harrison et al; Madduri et al Chari et al; Cohen et al ASH 2020

Treatment Options • All options need to be tried sequentially • No good data on optimum sequence or regimen • Cumulative toxicities from prior therapies may influence decision • All patients should be encouraged to participate in ongoing clinical trials

• • • • •

Summary and Future Directions Choice of therapy for RRMM depends on patient factors (frailty, comorbidity) and prior treatments (PI,IMiD,CD38MoAb) Triplet therapy for relapsed MM can achieve deep (including MRD-) durable responses BCMA CAR T and bispecific T cell engager therapies can achieve high rates of deep responses even in MM refractory to IMiD, PI, MoAb Since CD38 MoAb now incorporated into quadruplets with IMiD, PI, Dex , BCMA targeted therapies will move into treatment of earlier relapsed myeloma.

Long-term disease-free survival and potential cure of MM will require both MRD negativity, and restoration of host anti-MM immunity.

These patients will then be free of disease and off all therapy.

IMF Patient and Family Webinar

Supportive Care Updates: COVID, CAR T & More Patricia Mangan, RN, MSN, APRN-BC

Abramson Cancer Center University of Pennsylvania Philadelphia, PA 101

Supportive Care Updates: COVID, CAR T, and more Patricia A. Mangan, RN, MSN, APRN-BC Abramson Cancer Center University of Pennsylvania Patient & Family Webinar May 1, 2021

Your Care Team Is Here To Help You Stay Healthy

• You and your Subspecialists

caregiver are the center

General Hem/Onc

• Understand

their different roles

Primary Care Provider (PCP)

You and Your Caregiver(s)

Family/Support Network

Allied Health Staff

Myeloma Specialist

• Understand

how they can help you

2

Be an Empowered Patient • Participate in decisions • Ask for time to consider options (if needed/appropriate)

• Understand options - Use reliable sources of information - Use caution considering stories of personal experiences

• Create a dialogue • Express your goals/values/preferences • Arrive at a treatment decision together

Data From Research

HCP Clinical Experience TREATMENT DECISION

Your Preference Philippe Moreau. ASH 2015.

3

Think About Your Priorities and Questions Take Time to Consider Your Preferences Before an Appointment Ask Important Questions at Your Appointments • What Can I Expect Now? • What Can I Expect In the Future?

Have these conversations again… Ø Whenever your treatment stops working Ø Whenever you start a new treatment Ø Whenever there is a change in your life priorities Ø Whenever you have a question or concern 4

Communicate Effectively with Your Care Team Prepare for Your Away Mission

Achieve Your Appointment

• Consider telemedicine • Write down your questions and concerns • Bring current medications and supplements or a list • Any medical or life changes since your last visit?

• Current symptoms - how have they changed?

• Speak up!

• Ask your most important questions first • Understand your treatment plan and next steps • Have a list of who to contact and when • Bring a Caregiver for another “set of ears”

Navigate Home • Communicate with other members of your health care crew (pharmacist, others) • Take your medications as directed • Follow up with members of your heath care crew

5

Myeloma and Treatments Both Contribute to How You Feel Myeloma cells in excess can cause symptoms

Treatments for myeloma kill myeloma cells but can cause symptoms

• • • •

• • • •

Calcium elevation Renal dysfunction Anemia Bone pain

• Fatigue • Infection • Other symptoms

Myelosuppression Peripheral neuropathy Diarrhea Fatigue

• Deep vein thrombosis • Infection (eg, shingles) • Other symptoms

How You Feel 6

Explore Treatment Options & Plan Your Course Drug class Proteasome inhibitor Immuno-modulatory agent Monoclonal antibody Antibody-drug conjugate Nuclear export inhibitor Anthracycline Alkylating agents Alkylator conjugate HDACi CAR-T

Myeloma therapies Bortezomib (SQ) Carfilzomib Ixazomib Pomalidomide Lenalidomide Thalidomide Daratumumab Elotuzumab Isatuximab-irfc Belantamab mafodotin Selinexor Liposomal doxorubicin Cyclophosphamide Melphalan Melphalan flufenamide Panobinostat Ide-cel

This Photo by Unknown Author is licensed under CC BY-SA

7

CAR T-Cell Therapy: Patient’s Own T Cells Engineered CAR-T Therapy Patient T cells

Chimeric antigen receptor DNA

Grown in lab Reinfused in patient

• Different CAR-T products use different methods to engineer •

a patients own T cells to target myeloma cells BCMA (B-cell maturation antigen) is a protein found on the surface of myeloma cells that is targeted by several CAR-T products CAR-T Therapy ide-cel or Abecma

T-cell mediated death

NOW APPROVED!

cilta-cel P-BCMA-101 Myeloma cell

CD269 (BCMA) or other antigen

BCMA = B-cell maturation antigen; CAR-T = chimeric antigen receptor T cell; CRS = cytokine release syndrome.

Shah UA, Mailankody S. BMJ. 2020;370:bmj.m3176.

8

The Patient CAR-T Therapy Journey

Patient with multiple prior therapies

Consult with CAR-T Center

CAR-T Treatment Decision

May need a bridging therapy Harvest T Cells

Patient Waits ~4-6 weeks while Lab Grows Engineered T cells

Bridging therapy ongoing

Infuse Modif Cells Into Patiied T ent

Lab Engineers T Cells

Monitor Remain near CAR-T center up to 4 weeks

9

What is Cytokine Release Syndrome (CRS)?

Renal / Kidney

Hepatic / Liver

Respiratory

GI

Nausea Vomiting Diarrhea

Hematologic Musculoskeletal ­ CPK (bloodwork)

Cardiovascular Constitutional Fever Fatigue Headache

Early Recognition & Treatment are Essential

Muscle Pain Weakness

CRS

Neurologic Delirium Sleepiness Speech

ALP = alkaline phosphatase; CPK = creatine phosphokinase; CRP = C-reactive protein; CRS = cytokine release syndrome LDH = lactate dehydrogenase; O2, oxygen; TLS = tumor lysis syndrome.

Oluwole OO, Davila ML. J Leukoc Biol. 2016;100:1265-1272. June CH, et al. Science. 2018;359:1361-1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45-55.

Shimabukuro-Vornhagen, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.

10

Stress During a Pandemic Managing Stress During a Pandemic Stress during an infectious disease outbreak may sometimes cause the following: • Fear and worry about your own health and • • • • • •

the health of your loved ones Fear/worry about your financial situation or job, or loss of support services you rely on Changes in sleep or eating patterns Difficulty sleeping or concentrating Worsening of chronic health problems Worsening of mental health conditions Increased use of tobacco, and/or alcohol and other substances

CDC = Centers for Disease Control; COVID-19 = coronavirus 2019.

CDC website. How to Select, Wear, and Clean Your Mask. Accessed October 27, 2020.

Take care of your Mental Health • Take breaks from watching, reading, •

• •

or listening to news stories Take care of your body

– Take deep breaths, stretch, or meditate – Try to eat healthy, well-balanced meals – Exercise regularly – Get plenty of sleep – Avoid excessive alcohol and drug use Make time to unwind Connect with others. While social distancing measures are in place, consider connecting online, through social media, or by phone or mail

IMF has many resources to help you Download or order at myeloma.org

Videos

Website: http://myeloma.org

IMF TV Teleconferences eNewsletter: Myeloma Minute

IMF InfoLine: 1-800-452-CURE | 9am to 4pm PST

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