IMF Virtual Regional Community Workshop (RCW) - Pacific Northwest Region

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Welcome and Announcements Kelly Cox

Director Support Groups & Senior Director Regional Community Workshops 2

Thank you to our sponsors!

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Workshop Video Replay & Slides As follow up to today's workshop, we will have the speaker slides and a video replay available.

These will be provided to you shortly after the workshop concludes.

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Pacific Northwest REGIONAL COMMUNITY WORKSHOP Saturday October 9, 2021~ Agenda

10:00 AM - Welcome and Announcements Kelly Cox, Director Support Groups & Senior Director of Regional Community Workshops 10:05 AM - Myeloma 101 and Frontline Therapy Andrew Cowan, MD, Fred Hutchinson Cancer Research Center, Seattle, WA 10:40 AM - Q & A with Panel 10:55 AM – Meditation and Stretch Break 11:05 AM - Relapsed Therapy and Clinical Trials Craig Cole, MD, Michigan State University Breslin Cancer Center, Lansing, MI 11:45 AM - How to Manage Myeloma Symptoms and Side Effects Mary Steinbach, DNP, APRN, Huntsman Cancer Institute, Salt Lake City, UT, IMF Nurse Leadership Board 12:05 PM - Q&A with Panel

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Myeloma 101 and Frontline Therapy

Andrew Cowan, MD Fred Hutchinson Cancer Research Center, Seattle, WA 7

Myeloma 101 and Frontline Therapy Andrew Cowan, MD Associate Prof of Medicine, UW/Fred Hutch

Disclosures • Research Funding: Janssen, AbbVie, Bristol Myers Squibb, Harpoon, Sanofi, Nektar • Consultancy: Janssen, Celgene, Cellectar, Sanofi, Abbvie, GSK

Goals • Review myeloma basics • Review standards for initial treatment of multiple myeloma patients • Review important data on autologous HCT for multiple myeloma • Review standards for maintenance therapy in MM

What is multiple myeloma?

• Plasma cell neoplasm

• Characterized by malignant plasma cells infiltrating the bone marrow, and sometimes other organs and tissues • Symptoms depend on tumor burden and complications by plasma cell clones.

• The clones produce monoclonal immunoglobulin, cytokines, and other factors that interfere with bone metabolism, kidney function, hematopoiesis, immune mechanisms, and other organ systems

Eslick R, Talaulikar D. Multiple myeloma: from diagnosis to treatment. Aust Fam Physician. 2013 Oct;42(10):684-8.

Hematopoiesis

Alexander M. de Bruin et al. Blood 2014;124:2479-2486

©2014 by American Society of Hematology

The immunoglobulin molecule VL: light chain variable domain; CL: light chain constant domain; VH: heavy chain variable domain; CH1 CH3: heavy chain constant domains 1 - 3.

Serum protein electrophoresis (SPEP)

What are serum free light chains?

Epidemiology of multiple myeloma - USA Estimated New Cases in 2021

34,920

% of All New Cancer Cases

1.8%

Estimated Deaths in 2021

12,410

% of All Cancer Deaths

2.0%

Prevalence

149,956 people with myeloma in the USA

SEER Cancer Stat Facts: Myeloma. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/statfacts/html/mulmy.html

Clinical presentation of multiple myeloma • Signs or symptoms related to the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains • Anemia - 73 percent • Bone pain - 58 percent • Elevated creatinine- 48% • Fatigue/generalized weakness - 32 percent • Hypercalcemia - 28 percent • Weight loss - 24 percent, one-half of whom had lost ≥ 9 kg

“CRAB” Criteria Hypercalcemia Renal failure

Bone lesions

Anemia

Multiple myeloma - Diagnostic Criteria since 2014 • Clonal bone marrow plasma cells >10% OR biopsy proven plasmacytoma + “CRAB” Criteria (Classic) • • • •

HyperCalcemia Renal failure Anemia Bone lesions

• New additions with recent IMWG (Biomarker driven): • Serum free light chain ratio (involved/uninvolved) >= 100 • 1 or more focal bone lesions on MRI (> 5 mm in size) • > 60% clonal plasma cells on bone marrow examination Rajkumar et al Lancet 2014

Bone marrow MRI • MRI is more sensitive for detection of bone involvement than skeletal survey in MM • MRI detects involvement, but no bone destruction • MRI is less helpful for determining response to therapy; PET-CT and serum/bone marrow is better • MRI can detect spinal cord compression Dimopoulos JCO 2015

18F-FDG PET-CT • Can identify lytic lesions and extramedullary masses (out side bone masses) • Changes in uptake on serial PET can help assess response • In some cases, patients may be truly “non-secretory” and PET and/or MRI can be a valuable modality for assessing extent of disease • Mandatory to confirm the diagnosis of solitary plasmacytoma Cavo M, Terpos E, Nanni C, Moreau P, Lentzsch S, Zweegman S, Hillengass J, Engelhardt M, Usmani SZ, Vesole DH, San-Miguel J, Kumar SK, Richardson PG, Mikhael JR, da Costa FL, Dimopoulos MA, Zingaretti C, Abildgaard N, Goldschmidt H, Orlowski RZ, Chng WJ, Einsele H, Lonial S, Barlogie B, Anderson KC, Rajkumar SV, Durie BGM, Zamagni E. Role of (18)F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group. Lancet Oncol. 2017 Apr;18(4):e206-e217. doi: 10.1016/S14702045(17)30189-4. Review.

Incidence of chromosomal abnormalities in multiple myeloma Genomic aberration

Incidence, % (no. of patients analyzed for the aberration)

del(13)

48 (936)

t(11;14)(q13;q32)

21 (746)

t(4;14)(p16;q32)

14 (716)

Hyperdiploidy

39 (657)

MYC translocations

13 (571)

del(17p)

11 (532)

Avet-Loiseau et al, Blood 2007

Revised-International Staging System for Myeloma ISS or R-ISS ISS Criteria Stage I Serum beta-2 microglobulin < 3.5 mg/L, serum albumin ≥ 3.5 g/dL II Not ISS stage I or III III Serum beta-2 microglobulin ≥ 5.5 mg/L Palumbo et al, JCO 2015

R-ISS Criteria ISS Stage I AND standard risk CA by iFISH and normal LDH Not R-ISS stage I or III ISS Stage III AND either high-risk CA by iFISH or high LDH

What does “high-risk” myeloma mean?

• Outcomes for many patients with myeloma are improving • However, a subset of patients (20-25%) with certain biologic, genetic, and excess disease burden have poorer outcomes, even with novel agents and new therapies • New strategies to identify and offer more effective treatments for these patients are needed

Autologous HCT Eligible Induction

3 or 4 drug combinations including PI and IMiD, and CD38 antibody

Autologous transplantation, Early vs Deferred

Maintenance

Standard: Lenalidomide High risk: PI, or PI/IMiD/Steroid Combinations

Not Autologous HCT Eligible Induction

2 or 3 drug combinations

Supportive Care

Infectious prophylaxis VTE prophylaxis Bone Health – Bisphosphonates, RANKL inhibitors

Maintenance

What is the preferred upfront treatment approach?

• Induction with IMID/PI 3 drug combination, followed by autologous stem cell transplantation (Attal, NEJM 2017) • 4 drug induction including a monoclonal antibody – CASSIOPEIA – Dara-VTD, and GRIFFIN – DaraRVD; consider for high-risk patients • Maintenance therapy with IMID post transplant, for standard risk (McCarthy JCO 2017) • Maintenance therapy with PI / IMID based on SWOG high risk trial, Emory data • Intravenous bisphosphonates (MRC IX trial)

Multiple Myeloma Approved Drugs • Proteasome inhibitors • Bortezomib • Carfilzomib • Ixazomib

• Immunomodulatory agents • Lenalidomide • Pomalidomide • Thalidomide

• Selective Inhibitors of Nuclear Export (SINE) • Selinexor

• CAR T Cell Therapy

• Idecaptagene vicleucel (BCMA CAR T)

• Monoclonal antibodies • • • •

Daratumumab (CD38) Isatuximab (CD38) Elotuzumab (SLAMF7) Belantamab mafodotin (BCMA) (Aug 2020)

• Alkylating agents • • • •

Melphalan Cyclophosphamide Bendamustine Melflufen (Q1 2021)

• HDAC Inhibitors • Panobinostat

ENDURANCE: RVd vs KRd, ASCO 2020

GRIFFIN (NCT02874742): Randomized Phase 2 • Phase 2 study of D-RVd vs RVd in transplant-eligible NDMM, 35 sites in US with enrollment from 12/2016 and 4/2018 Induction: Cycles 1-4 D-RVd

• Transplanteligible NDMM • 18-70 years of age • ECOG score 02 • CrCl ≥30 ml/mina

1:1 Randomization

Key eligibility criteria:

D: 16 mg/kg IV Days 1, 8, 15 R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2, 8, 9, 15, 16

RVd

R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2 ,8, 9, 15, 16

T R A N S P L A N T

Consolidation: Cycles 5-6c

Maintenance: Cycles 7-32d

D-RVd

D-R

D: 16 mg/kg IV Day 1 R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2, 8, 9, 15, 16

RVd

R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2, 8, 9, 15, 16

21-day cycles

21-day cycles

D: 16 mg/kg IV Day 1 Q4W or Q8We R: 10 mg PO Days 1-21 Cycles 7-9; 15 mg PO Days 1-21 Cycle 10+

R

R: 10 mg PO Days 1-21 Cycles 7-9; 15 mg PO Days 1-21 Cycle 10+

28-day cycles

Stem cell mobilization with GCSF ± plerixaforb

Voorhees P et al. ASH Annual Meeting, Orlando, 2019

Endpoints & statistical assumptions Primary endpoint:

sCR (by end of consolidation); 1-sided alpha of 0.1 80% power to detect 15% improvement (50% vs 35%), N = 200

Secondary endpoints:

MRD (NGS 10–5), CR, ORR, ≥VGPR

Primary Endpoint: sCR by the End of Consolidationa Post-consolidation depth of responsea

• Primary endpoint met at pre-set 1-sided alpha of 0.1 

sCR by end of consolidation

PR

− 42.4% D-RVd vs 32.0% RVd

50 40

42.4

10 0

70 60 50

32.0

20 10 0

D-RVd (n = 99)

RVd (n = 97)

≥CR: 51.5% ≥VGPR: 90.9%

42.4

9.1

40 30

30 20

80

Patients (%)

Patients (%)

60

ORR = 91.8%

90

sCR: 1-sided P = 0.068b

70

sCR

ORR = 99.0%

100

100 80

CR

ORR: 2-sided P = 0.0160b

− Odds ratio, 1.57; 95% CI, 0.87-2.82; 1-sided P = 0.068b 90

VGPR

39.4

8.1 D-RVd (n = 99)

Voorhees P et al. ASH Annual Meeting, Orlando, 2019

sCR: 1-sided P = 0.068b

32.0 10.3 30.9

18.6 RVd (n = 97)

≥CR: 42.3% ≥VGPR: 73.2%

Responses Deepened Over Timea sCR Odds Ratio: P = 0.0253b ≥CR Odds Ratio: P = 0.0014b 100 90

Patients (%)

80

12.1 7.1

≥CR: 19.2%

6.1

70 60 50

21.2

≥CR: 27.3%

52.5

0

≥CR: 51.5%

63.6

39.4 26.3

2.0 End of induction

12.1 End of ASCT

1.0

8.1

1.0

End of consolidation

14.1 3.0

14.4 5.2

≥CR: 19.6%

1.0

12-months-ofmaintenance cutoff

D-RVd

32.0

≥CR: 42.3%

≥CR: 60.8%

13.4

30.9 35.1

47.4

10.3

46.4

sCR CR VGPR PR SD/PD/NE

18.2

≥CR: 13.4%

43.3

≥CR: 81.8%

59.6

30

10

42.4

9.1

40

20

7.2 6.2

18.6 25.8

18.6

13.4

8.2

8.2

8.2

7.2

End of induction

End of ASCT

End of consolidation

12-months-ofmaintenance cutoff

RVd

• Results for end of induction, ASCT, and consolidation are based on a median follow up of 13.5 months at the primary analysis • Median follow up at 12-months-of-maintenance therapy cutoff was 27.4 months

Response rates and depths were greater for D-RVd at all time points aData

shown for response-evaluable population. bP values (2-sided) calculated using Cochran–Mantel–Haenszel chi-square test.

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Induction Therapy for MM in 2021: Summary • Addition of daratumumab to RVd backbone results in higher proportion of sCR • Daratumumab-RVd also resulted in increased rates of MRD (10-5) negativity • In practice, I have used this most often amongst the high-risk MM patient population, where achievement of sustained MRD negativity is critical • High risk: t(4;14), t(14;16), Del(17p), Plasma cell leukemia, t(14;20)

Treatment of non-transplant eligible myeloma, newly diagnosed • Consider triplet combination, or

• IMID/PI Triplet combination – RVD lite • Daratumumab, lenalidomide, dexamethasone – MAIA trial

• Consider doublet for frail/elderly

• Lenalidomide/low dose dexamethasone • Bortezomib/low dose dexamethasone

• Other options

• Alkylator/PI combination (CyBorD) • Daratumumab+VMP (ALCYONE Trial, NEJM 2018) **

Autologous stem cell transplantation for multiple myeloma • Remains a cornerstone of management for eligible newly diagnosed patients – randomized trials show benefit for PFS • Recommend early or delayed transplant, rather than no transplant after induction therapy • Very low treatment related mortality in modern era (1-2%) • Acute regimen toxicities (mucositis, infections, diarrhea) are manageable

Transplant eligible vs ineligible • What factors are important?

• Age – not an absolute contraindication • Comorbidities, general level of health (“eyeball test”) • Patient preference • Caregiver, occupation, support system, residence

Updates from ASH: IFM-2009 and FORTE trial Updated data from IFM-20091:

Updated analysis from the FORTE trial2 KRd induction-ASCT-KRd consolidation (KRd_ASCT) vs 12 cycles of KRd (KRd12) vs KCd induction-ASCT-KCd consolidation (KCd_ASCT) and the PFS of KR vs R maintenance.

1Gay

F, et al, ASH 2020; 2Perrot A et al, ASH 2020

Summary – Lenalidomide Maintenance PostASCT • Lenalidomide maintenance post ASCT improved PFS in several large studies • Lenalidomide maintenance post-ASCT improved OS in one study (McCarthy et al) • Meta analysis of 3 RCTs showed OS benefit with lenalidomide maintenance

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Summary – Bortezomib maintenance for high-risk myeloma • Aggregate data from analysis of the HOVON-65/GMMG HD4 trial indicates a benefit for bortezomib maintenance post ASCT, given every 2 weeks for 2 years, particularly for those patients with the following chromosomal abnormalities: • Del(17p) • t(4;14)

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RVd Maintenance for high-risk MM

Usmani S et al. EHA Annual Meeting 2020

Summary • Outcomes continue to improve for newly diagnosed multiple myeloma!

• Be sure to consult with an MM specialist at some point – the field is changing rapidly • Standards are evolving, but autologous stem cell transplantation remains a cornerstone of effective upfront treatment for eligible patients • Addition of CD38 antibodies may improve outcomes – increased rates of MRD negativity and deeper responses tend to result in better long-term survival

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Audience Q&A with Panel

• Open the Q&A window, allowing you to ask questions to the host and panelists. They can either reply to you via text in the Q&A window or answer your question live.

• If the host answers live, you may see a notification in the Q&A window.

• If the host replies via the Q&A box – you will see a reply in the Q&A window.

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We will begin with a 5-minute mindful meditation and then go into a 5-minute break For more guided audio and video meditations, and guided yoga, please visit our website: https://wellness.myeloma.org/mind-body/ Meditation is led by Kelley Sidorowicz, IMF Regional Director, Support Groups

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Welcome Back!

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Agenda After the Break Relapsed Therapy and Clinical Trials Craig Cole, MD, Michigan State University Breslin Cancer Center, Lansing, MI How to Manage Myeloma Symptoms and Side Effects Mary Steinbach, DNP, APRN, Huntsman Cancer Institute, Salt Lake City, UT, IMF Nurse Leadership Board Q&A with Panel

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Relapsed Therapy and Clinical Trials

Craig Cole, MD

Michigan State University Breslin Cancer Center, Lansing MI 47

The Application of Science…

Approach to Relapsed Myeloma and New Therapies and Clinical Trials

International Myeloma Foundation Regional Community Workshop Seattle WA and Surrounding Region Saturday October 9, 2021 10:00 AM PT – 12:30 PM PT Craig Emmitt Cole, MD

Assistant Professor of Medicine Director of Clinical Research-Breslin Cancer Center Division of Hematology/Oncology Department of Medicine College of Human Medicine Michigan State University

Today’s Discussion • What is Relapsed Myeloma • Treating Relapsed Myeloma

• Conditions influencing selection • Options of Therapy

• The Antibodies

• Daratumumab • Elotuzumab • Isatuximab

• NEW STUFF……

• Antibody Drug Conjugates (ADC) • CAR-T cell and other novel immune Therapies!

• BiTE Antibodies

• Clinical Trials

What is Relapsed Multiple Myeloma ?

• Relapsed multiple myeloma is when the cancer returns after treatment.

• Usually after a period of remission or response.

Relapsed = Recurrent =Progressive • Since multiple myeloma does not have a cure, it is likely that at some point patients will have a relapse.

• With therapy, relapsed myeloma patients can achieve a second response.

• Refractory myeloma is when myeloma is not responsive to therapy.

The Typical Course of Myeloma

Disease Burden (M-Protein)

Diagnosis Myeloma

1st

2nd Line of Therapy

Line of Therapy

Induction Therapy

Progressive disease “Relapsed” Symptomatic

L T o i n m g e

C R A B

2nd Treatment Possible Auto Transplant

Biochemical Progression ↑- 25% from lowest point ↑-M-protein by 0.5 ↑>10mg difference Free Lite

Continued Treatment

2nd

Maintenance

Treat or Watch: Treat if doubles in 3mo

Plateau Remission

Time

3rd, 4th, 5th Treatment

Refractory!

Treat

30 Drugs approved by the FDA with 14 new agents!

Conditions influencing the selection of treatment for patients with relapsed/refractory myeloma Disease-related • Duration of response to last therapy.

• C.R.A.B. symptoms • Kinetics of relapsed disease •

Rapid progression vs. slow progression

High Risk Relapse • High LDH • Disease outside bone/ bone marrow • Translocations t(4:14), del(17p), and del(13q14) mutations • Secondary mutations •

Patient-related • • • • • •

Age Level of activity Neuropathy Blood counts Kidney impairment Recent blood clots, heart attack, stroke events

RAS, FGFR3, MYC, or loss or mutation in TP53 Mayo Clin Proc. 2017;92(4):578-598

Regimen-related • Number of previous lines of therapy.

• Relapsing while on or off maintenance.

• Previous drug exposure (new vs. classic agents) • Previous transplant with short <3yrs vs. prolonged response >3yrs.

Which Therapy is the Right Therapy for YOU? Age

Lifestyle Goals of Therapy

Patient Preference

Myeloma Symptoms

Treatment Options For Relapsed Myeloma 1st Relapse on Revlimid Maintenance Dara+Velcade+Dex Dara+Pomalyst+Dex Dara+Kyprolis+Dex Elotuzumab+Pomalyst+Dex Kyprolis+Pomalyst+Dex Elotuzumab+Velcade+Dex Ninlaro+Pomalyst+Dex Ninlaro+Cytoxan+Dex Velcade+ Cytoxan+Dex Velcade+ Pomalyst+Dex Isatuximab(Sarclisa)+Pomalyst+Dex Isatuximab(Sarclisa)+Kyprolis+Dex Followed by…1st or 2nd Stem Cell Transplant

1st Relapse on Velcade Maintenance Dara+Revlimid+Dex Elotuzumab+Revlimid+Dex Kyprolis+Revlimd+Dex Kyprolis+Pomalyst+Dex Dara+Pomalyst+Dex Dara+Kyprolis+Dex Elotuzumab+Pomalyst+Dex Isatuximab(Sarclisa)+Pomalyst+Dex Isatuximab(Sarclisa)+Kyprolis+Dex

CLINICAL TRIALS 1st Relapse off Tx or Maintenance

Followed by…1st or 2nd Stem Cell Transplant

Any of the above

Mayo Clin Proc. 2017;92(4):578-598; Leukemia (2018) 32, 252–262

Treatment Options For Relapsed Myeloma 2nd or Later Relapsed

Dara+Pomalyst+Dex Kyprolis+Pomalyst+Dex Cytoxan+Pomalyst+Dex Ninlaro+Pomalyst+Dex Elo+Pomalyst+Dex Elo+Thaliomide+Dex Dara+ Thalidomide+Dex Dara+Kyprolis+Dex Kyprolis+Revlimid+Dex Elo+Revlimid+Dex Dara+Revlimid+Dex Dara+Velcade+Dex Elo+Velcade+Dex Panobinostat+thalidomide+velcade+dex Cytoxan+Kyprolis+Thalidomide+dex Selinexor+Dex Selinexor+Velcade+Dex Isatuximab(Sarclisa)+Pomalyst+Dex Isatuximab(Sarclisa)+Kyprolis+Dex Darzalex FASPRO (given under skin) with above therapies

>4 prior lines of therapy Aggressive Relapsed or Refractory Selinexor+Dex Selinexor+Velcade+Dex Belantamab mafodotin Melphalan Flufenamide Abcma (Ida-cel) CAR-T

Allogeneic Stem Cell transplant

CLINICAL TRIALS!

Mayo Clin Proc. 2017;92(4):578-598

Clinical Trials

What are we talking about?

Definitions in Myeloma Treatment….

Did it work? Response Criteria • Complete response (CR) •

Treatment outcome where there are ≤5% plasma cells in the bone marrow and no evidence of laboratory myeloma proteins in the serum or urine

• Very good partial response (VGPR) •

Treatment outcome where there is a >90% decrease in M protein

• Partial response (PR)

• Treatment outcome where there is a >50% decrease in M protein

• Stable disease (SD)

• No change in Myeloma protein but has not progressed.

How long did it work/ what are the side effects?

OS: Overall Survival PFS: Progression-Free Survival (@how long the treatment worked) AE: Adverse Events- Side effects

The Immune Therapies

Targets on the Myeloma Cell Surface and Therapeutic Antibodies Antibody Drug

Antibody Drug: Dacetuzumab, Lucatumumab

Indatuximab Ravtansine

CD40

CD138

SLAMF7

CD38

Antibody Drug Daratumumab Isatuximab MOR-202

Antibody Drug Elotuzumab BiTE Antibodies CAR-T

BCMA

Antibody Drugs ABCMA Other CAR-T BiTE antibodies Blenrep (ADCs)

BMJ. 2020 Sep 21;370:m3176. doi: 10.1136/bmj.m3176.

Manufactured Antibody Targeting of Myeloma Antibody and Immune System Attack

Increase production of cytoxic T-cells

T-Cells Good Guys

Natural Killer Cell Good Guys

Manufactured Anti-Myeloma Myeloma Antibody surface targets

Antibody Receptor

Complement Protein Attack Myeloma Cells

Attacking the Myeloma Cell Biology

Complement Proteins

Inhibition of adhesion between the myeloma and bone marrow stromal cells

Drug Empliciti (elotuzumab)

Monoclonal Antibodies Delivery

Indication

IV once a week for first 8 weeks; then every 2 weeks

• For relapsed/refractory myeloma in combination with Revlimid or Pomalyst and dexamethasone

Darzalex (daratumumab)

IV or Subq once a week for first 8 weeks; then every 2 weeks for 4 months, then monthly • The first prescribed IV dose may be split over 2 consecutive days

• As a single agent for relapsed/refractory myeloma • For relapsed/refractory myeloma in combination with Revlimid, Pomalyst, Kyprolis, or Velcade and dexamethasone • For newly diagnosed patients who are eligible for transplant in combination with – Velcade, Thalomid, and dexamethasone • For newly diagnosed patients who are ineligible for transplant in combination with – Velcade, melphalan, and prednisone – Revlimid and dexamethasone

Sarclisa (isatuximab)

IV once a week for first 4 weeks; then every 2 weeks

• For relapsed/refractory myeloma in combination with Pomalyst, Kyprolis and dexamethasone

Antibody–Drug Conjugate Belantamab mafodotin (Blenrep)

IV once every 3 weeks.

•

For relapsed/refractory myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody

Performance of Daratumumab= Dara=Darzalex Phase

Regimen

#Pts

Daratumumab Revlimid Dex Vs. Rev/dex.

3

569

Daratumumab Velcade Dex Vs. Velcade/Dex.

3

Daratumumab Pomalyst Dex

Ib

1b

Type of patients

Outcomes

Average of 1 prior Line of therapy

Dara + Rev/dex vs. Rev/Dex

POLLUX

≥Complete Response (55% vs 22%) Time to relapse (PFS): DRD not reached DRd reduced risk progression or death by 56% vsRd

• • • • • •

Low WBC, Muscle spasms Fatigue Diarrhea Infection:39% Infusion reactions:56%

Average of 2 prior line of therapy

Dara+Velcade/dex vs Vel/dex:

• • • • • •

Low platelets Fatigue neuropathy, Diarrhea Anemia Infusion reactions: 45%

77

Average of 4 prior lines of therapy

Response rate: 60% PR: 18% VGPR: 28% Complete response or better: 17% Response rate of 57.5% in patients who failed Rev and Velcade

• • • • • •

Neutropenia, anemia, fatigue, Cough Nausea diarrhea Infusionreactions: 50%

85

Average of 2 prior line of therapy

Proir Revlimd Overall response: 90% VGPR:35% Refractory Revlimid: Overall Response: 79% VGPR:50%

• Neutropenia, • Anemia • Low platelets • High BP “manageable cardiac problems”

498

CASTOR

EQUULEUS Daratumumab Kyprolis Dex

Response rate DRD:93% vs.

Response rate RD: 76%

Adverse Events

Response rate DVD:84% vs.

Response rate Vd:63% ≥VGPR (62% vs 29%) ≥CR (19% vs 9%)

Dimopoulos MA, et al. ASH 2017. Abstract 739; N Engl J Med 2016; 375:754-766; Blood 2017,130:974-981; Cancer 2019 May 15:1-9

Regimen

Phase

Performance of Empliciti =(Elotuzumab)= “Elo” Patient #s

Number of prior line of Tx

Outcomes

646

Average of 2 prior lines of therapy

EloRD vs. RD

Elotuzumab + Revlimid+ Dex Vs. Rev Dex

3

Elotuzumab +Velcade + Dex vs.

Velcade Dex

2

152

Elotuzumab +Pomalyst + Dex vs.

Pomalyst+Dex

2

117

Elotuzumab +Kyprolis + Dex

2

11

Response rate: EloRD:79% vs RD:66%

Median Duration of response: Elo RD:19.4 vs RD:14.9 months

Adverse Events

Severe toxicities: • Low lymphocytes, • fatigue, • Pneumonia • Infusion reaction in 10% of patients

1 to 3 prior regimens

EloVD vs. VD

Response rate: Elo VD:65% vs VD: 63% Median Duration of response: EloVD:9.9 vs VD:6.8 months

Severe toxicities: Low platelets (9%), infections (23%) •• Infusion reaction in 5% of patients

Median 3 prior regimens

EloPD vs. PD

Most common: fatigue, infections, cough, anemia Toxicities: Infections(65%),

Response rate: Elo PD:53% vs PD: 27% Median Duration of response: EloPD:10.3 vs PD:4.7 months

ORR is 91% 3 patients in VGPR 7 patients in PR,

• • •

Fatigue: 38% Upper resp infection: 38% Low platelets: 17%

N Engl J Med 2015; 373:621-631; Abstract#142;2017 Lymphoma & Myeloma (L&M) Annual Meeting; Blood 2016 127:2833-2840; Abstract#215311; 2018 ASCO Annual Meeting; N Engl J Med 2018; 379:1811-1822; Blood 2018 November 29, 2018;132 ASH Abstract#1975

Antibody Drug Conjugates (ADC) in Myeloma Chemotherapy agent Linker Monoclonal Antibody

Belantamab mafodotin IV humanized anti-BCMA ADC ● ● ●

●

Belantamab mafodotin (Blenrep) is an IV humanized anti-BCMA monoclonal antibody conjugated to monomethyl auristatin-F In the phase II DREAMM-2 trial, belantamab mafodotin 2.5 mg/kg every 3 weeks showed deep and durable responses with a manageable safety profile Approved in August 2020 by the FDA and EMA for treating patients with R/R MM who have received ≥ 4 previous therapies, including an anti-CD38 mAb, a Proteosome Inhibitor (PI) , and an IMiD Eye toxicity events known to occur with belantamab include keratopathy (disease of the cornea), changes in visual acuity, and other ocular symptoms (eg, blurred vision, dry eye) ○

Prior to each dose patient require a brief eye exam required by the Risk Evaluation and Mitigation Strategy (REMS), called the BLENREP REMS Blood Cancer Journal 2019 vol 9, number 37.p 2-10

DREAMM-2 Open-label, randomized phase II trial of Belantamab Mafodotin (Blenrep) Response Rate Efficacy Endpoints

3-6 Prior Lines of Tx (n = 47)

≥ 7 Prior Lines of Tx (n = 50)

ORR, % (97.5% CI)

34 (19.3-51.4)

30 (16.5-46.6)

OS, mos (95% CI)

13.7 (9.1-NR)

13.4 (8.7-NR)

11.0 (4.2-NR)

13.1 (4.0-NR)

Median DoR, mos (95% CI) Probability of PFS at 6 mos, % (95% CI)

35 (20-50)

30 (17-43)

All Patients (n = 97) 31 (21.7-43.6) 13.7 (9.9NR) 11.0 (4.2NR) 32 (22-42)

Lonial. ASH 2020. Abstr 1417.

Patients With Response (%)

45 40 35 30

CR: 4% VGPR: 13%

25

CR: 6%

20 15

PR: 17%

10 5 0

sCR: 4%

VGPR: 10% PR: 10%

MR: 6%

3-6 Prior Lines of Tx (n = 47)

MR: 2%

≥ 7 Prior Lines of Tx (n = 50)

DREAMM-2: Common Adverse Events Associated With Belantamab Mafodotin (Blenrep) Adverse Events (AE) in > 10% of Patients, n (%) Any AE Ocular AE  Keratopathy (corneal changes)  Blurred vision Hematologic AE  Thrombocytopenia  Anemia  Lymphocytopenia  AST increased

3-6 Prior Lines of Therapy (n = 46)

≥ 7 Prior Lines of Therapy (n = 49)

All Patients (n = 95)

Any Grade 44 (96)

Grade 3/4 36 (78)

Any Grade 49 (100)

Grade 3/4 43 (88)

Any Grade 93 (98)

Grade 3/4 79 (83)

32 (70) 12 (26)

15 (33) 3 (7)

35 (71) 9 (18)

13 (27) 1 (2)

67 (71) 21 (22)

28 (29) 4 (4)

11 (24) 8 (17) 6 (13) 11 (24)

8 (17) 5 (11) 5 (11) 0 (0)

12 (24) 18 (37) 7 (14) 9 (18)

10 (20) 15 (31) 7 (14) 2 (4)

23 (24) 26 (27) 13 (14) 20 (21)

18 (19) 20 (21) 12 (13) 2 (2)

DREAMM-2: disrupted vision returned to baseline in 81% of affected patients Lonial. ASH 2020. Abstr 1417.

DREAMM-6: Study Design (Belantamab+Velcade+Dex Arm) Part 2: Dose Expansion (Max 8 Cycles)

Part 1: Dose Escalation Measurable R/R MM, ≥1 prior therapy; prior ASCT allowed or transplant ineligible; ECOG PS 0-2

Belantamab Mafodotin 3.4 mg/kg single* + Velcade † x 21-day cycles (n = 6) Belantamab Mafodotin 2.5 mg/kg single* + Velcade† x 21-day cycles (n = 6)

Belantamab Mafodotin 2.5 mg/kg single day + Velcade † x 21-day cycles (n = 12) Belantamab Mafodotin 2.5 mg/kg days 1 ,8 + Velcade † x 21-day cycles (n = 12) Belantamab Mafodotin 3.4 mg/kg single day + Velcade † x 21-day cycles (n = 9) Belantamab Mafodotin 3.4 mg/kg days 1, 8 + Velcade † x 21-day cycles (n = 12)

Nooka. ASCO 2020. Abstr 8502.

All Arms Single-agent belantamab until PD, death, toxicity, or consent withdrawal

DREAMM-6: Belantamab+Velcade+Dex Arm  All patients had evaluable responses

Best Confirmed Response, n (%)

 ORR: 78% (95% CI: 52.4-93.6)

Clinical benefit rate ‒ Higher than previously reported ORRs for Vd in patients with ≥ 1 prior Overall Response Rate (ORR) therapy (50% to 63%)

Belantamab mafodotin + Vd (N = 18) 15 (83) 14 (78)

 Median duration of response not yet reached

 VGPR

9 (50)

 PR

5 (28)

 Main adverse events of interest: keratopathy, thrombocytopenia

MR

1 (6)

SD

3 (17)

Nooka. ASCO 2020. Abstr 8502. Palumbo. NEJM. 2016;375:754. San Miguel. Lancet Oncol. 2014;15:1195. Richardson. Lancet Oncol. 2019;20:781.

I attack invaders outside the cells!

The Horizon is Bright!

I attack misbehaving and mutated cells!

CAR –T Immune Therapy

Program patient’s T-cells with CAR cell therapy 101 T cellsCAR-T are the a type of white blood cell that attack and to kill viruses and cancer cells recognize and destroy the patient’s own Chimeric antigen receptors (CARs) help T-cells recognize and I hope… cancer cells destroy cancer cells T-cells Virus with CAR Gene

Pt’s T cell

CAR Gene

T-cell

Now expressing Cancer hunting CAR Receptor

New CAR T-cells

CAR-BCMA T-Cells in Myeloma: Background • B-cell maturation antigen (BCMA) is expressed myeloma cells and is a potential target for CAR T-cell therapy for MM. • T cells can be genetically modified to express chimeric antigen receptors (CARs) specific for BCMA or other proteins associated with cancer.

• The patient’s own T-cells are stimulated, transduced with BCMA retroviruses, and cultured for 9-14 days before re-infusion.

• The CAR-T cells engage myeloma cells thru BCMA.

T Cell AntiBCMA T Cell AntiBCMA

AntiBCMA Receptor

T Cell T Cell

AntiBCMA

AntiBCMA

BCMA

– T-cells are activated and then kill the myeloma cells – The CAR-T cells also have another built-in switch which causes the CAR-Ts to expand in number and potency J Clin Oncol 35, 2017 (suppl; abstr LBA3001); 22nd EHA Congress; June, 2017;Abstract S142; Cohen AD, et al. ASH 2017. Abstract 505

Toxicities of CAR-T:

Cytokine Release Syndrome and Neurotoxicity • • •

Cytokine Release Syndrome (CRS) is a severe inflammation reaction related to T-cell engagement to the target CRS can be mild (grade 1) to severe (grade 4) causing multisystem organ failure The cause of the neurotoxicity is unknown

Idecabtagene vicleucel (Ida-cel) BCMA-directed CAR T-cell therapy • Multicenter KarMMa Phase II trial in pts with R/R MM who received ≥ 3 prior lines of therapy.

• Treatment approach: 6 50 x 10 bb2121 CAR T-cells

T-cell apheresis to collect cells to construct bb2121 CAR-T

3 days of Chemo with Fludarabine and Cyclophosphamide

150 x 106 bb2121 CAR T-cells 450 x 106 bb2121 CAR T-cells

•

128 consecutive patients who received Ida-cel (bb2121) infusion were reported • • •

• •

The median age was 61 years (range, 33 to 78) 35% had a high-risk cytogenetic profile Median number of previous regimens was 6

The manufacturing of Ida-cel was successful for 99% of the patients Anti-BCMA CAR was expanded over a period of 10 days Raje N et al. JG N Engl Med 2019;380:1726-1737 Berdeja et al. JASH 2017.

Abstract 740.

Ida-cel CAR-T : Overall Response Rate Outcome

Ide-cel 150 x 106 (n = 4)

Ide-cel 300 x 106 (n = 70)

Ide-cel 450 x 106 (n = 54)

All Ide-cel Patients (n = 128)

ORR, n (%)

2 (50)

48 (69)

44 (81)

94 (73)

CR/sCR, n (%)

1 (25)

20 (29)

21 (39)

42 (33)

Outcome by Prior Lines

3 Lines Tx (n = 15)

≥4 LinesTx (n = 113)

All Ide-cel Patients (n = 128)

ORR, n (%)

73

73

73

CR/sCR, n (%)

53

30

33

VGPR

0

23

20

PR

20

20

20



Median follow-up: 24.8 mo (range: 1.7-33.6 mo)



Median Duration of response 10.9 mo (9.0-11.4)



Median PFS at 300 x 106 CAR T-cells was 5.8 mo vs 12.2 mo with 450 x 106 CAR T-cells Anderson. ASCO 2021. Abstr 8016.

Ida-cel CAR-T : Toxicity 3 Prior Therapy Lines (n = 15)

≥4 Prior Therapy Lines (n = 113)

All Ide-cel Patients (n = 128)

≥1 event, n (%)

13 (87)

94 (83)

107 (84)

Median onset, days (range)

1 (1-2)

1 (1-12)

1 (1-12)

Median duration, days (range)

4 (1-63)

6 (2-28)

5 (1-63)

Incidence of Cytokine Release Syndrome

Characteristics of Neurotoxicity

Grade 1 (n = 11)

Grade 2 (n = 7)

Grade 3 (n = 5)

Median time to first onset, days (range)

2 (1-10)

2 (1-4)

2 (1-4)

Median duration of NT per event, days (range)

2.5 (1-9)

Events by duration %  1-5 days  6-10 days  > 10 days  Ongoing

75 25 0 0

5.5 (1-26)

43 29 14 14

8.5 (2-22)

50 0 50 0

Signs and Symptoms in Patients With Neurotoxicity, n (%)*

All Ide-cel Patients(n = 128) Any Grade (n = 23)

Grade 3(n = 5)

Confusional state

12 (9.4)

1 (0.8)

Encephalopathy

7 (5.5)

3 (2.3)

--

1 (0.8)

Aphasia

6 (4.7)

1 (0.8)

Hallucination

4 (3.1)

--

Mental status changes

4 (3.1)

1 (0.8)

Delirium

3 (2.3)

--

Lethargy

3 (2.3)

1 (0.8)

Tremor

3 (2.3)

--

Hemiparesis

2 (1.6)

1 (0.8)

Metabolic encephalopathy

Anderson. ASCO 2021. Abstr 8016.

Idecabtagene vicleucel (Ida-cel) BCMA-directed CAR T-cell therapy  Idecabtagene vicleucel BCMA-directed CAR T-cell therapy FDA approved for R/R MM after ≥4 previous lines of therapy, including an IMiD, a PI, and an anti-CD38 mAb ‒ FDA approval based on pivotal phase II KarMMA study that assessed efficacy and safety of ide-cel in R/R MM  In patients with R/R MM, use of idecabtagene vicleucel CAR T-cell therapy in KarMMA trial continued to result in durable responses, regardless of number of prior therapy lines ‒ Median follow-up of 24.8 mo: ORR in all patients, 73%; CR/sCR, 33% ‒ Median DoR: 10.9 mo; median PFS: 8.6 mo ‒ Median OS: 24.8 mo, and >20 mo in most subgroups at high risk of progression Chari. NEJM. 2019;381:727. Lonial. Lancet Oncol. 2020;21:207. Raje. NEJM. 2019;380:1726. Anderson. ASCO 2021. Abstr 8016

Results of Selected CAR-T Clinical Trials for RR Myeloma Study

#pt enrolled

Phase of trial

Product

Lines of prior treatment, median (range

CRB-401

69

1

Ide-cel (bb2121)

7 (3-23)

76

6

75.8

72

38.7

94 (15/16; ≥PR patients)

11.8 mo

N/A

KarMMA

128

2

Ide-cel (bb2121)

6 (3-16)

84

6

73

53

33

33 (26/128; CR patients)

8.8 mo

19.4 mo

3 (1-9)

90

7

89

78

74

68.4 (39/57; CR patients)

19.9 mo

36.1 mo

6 (3-18)

93

4

97

97

80

81 (13/16; 87% (9 mo) CR patients)

100

12.5

93%

89

3

92

LEGEND-2

CARTITUDE-1

GC012F

EVOLVE

57/74

97

1

1b/2

LCAR-B38M Cilta-cel (JNJ68284528)

Dual CAR-T BCMA+CD19

16

62

LCAR-B38M (JNJ68284528)

1

Orvacabtagen e autoleucel (JCARH125)

6 (3-18)

CRS any grade, %

CRS grade ≥3, %

ORR, %

≥VGPR, %

CR, %

MRD PFS, median OS, median negative, %*

56.3%

68

35

Hematology Am Soc Hematol Educ Program 2020; 2020 (1): 272–279

96 (21/25) at 3 mo (≥PR patients)

N/A

N/A

N/A

N/A

N/A

Bi-specific T-cell engagers (BiTEs) antibodies to bring the activated T cells to the cancer Anti-CD3 (T-Cell) monoclonal antibody

Cytotoxic granule

T Cell CD3

BiTE antibody

composed of two single-chain antibodies

Anti-tumor monoclonal antibody (such as BCMA or CD19)

BCMA

MagnetisMM-1:Elranatamab (PF-3135) Elranatamab 1000 µg/kg QW (n = 6) • Elranatamab is a bispecific antibody targeting BCMA on MM cells and CD3 on T-cells • MagnetisMM-1 is a phase I trial to evaluate the safety, and efficacy of elranatamab in patients with R/R MM

Elranatamab 600 µg/kg QW (n = 6) Elranatamab 360 µg/kg QW (n = 4) Elranatamab 215 µg/kg QW (n = 4)

Patients with R/R MM and prior tx with IMiD, PI, and anti-CD38 mAb -Prior BCMA-directed therapy allowed (N = 30)

Subcutaneous Elranatamab 130 µg/kg QW (n = 4) dosing Elranatamab 80 µg/kg QW (n = 6)

Bahlis. ASCO 2021. Abstr 8006.

MagnetisMM-1: Response Rates 215 mg/kg (n = 4)

360 mg/kg (n = 4)

600 mg/kg (n = 6)

1000 mg/kg* (n = 6)

Total (≥215 mg/kg) (n = 20)

Confirmed ORR  sCR  CR  VGPR  PR  MR

2 (50.0) 2 (50.0) 0 0 0 0

3 (75.0) 1 (25.0) 0 2 (50.0) 0 0

4 (66.7) 2 (33.3) 0 2 (33.0) 0 0

5 (83.3) 0 1 (16.7) 3 (50.0) 1 (16.7) 0

14 (70.0) 5 (25.0) 1 (5.0) 7 (35.0) 1 (5.0) 0

SD

2 (50.0)

0

1 (16.7)

0

3 (15.0)

PD

0

1 (25.0)

1 (16.7)

1 (16.7)

3 (15.0)

Response, %

   

Median time to response: 22 days (range: 21-50); median duration of response has not been reached Probability of responders being event-free at 6 months: 92.3% (95% CI: 56.7%-98.9%) Patients with prior BCMA-directed therapy achieved response: 2 VGPR and 1 sCR (n = 4) 3 patients assessed were MRD negative Bahlis. ASCO 2021. Abstr 8006.

MagnetisMM-1: Cytokine Release Syndrome (CRS) CRS, % Overall  Grade 1  Grade 2

80 mg/kg (n = 6)

130 mg/kg (n = 4)

215 mg/kg (n = 4)

360 mg/kg (n = 4)

600 mg/kg (n = 6)

1000 mg/kg (n = 6)

Total (N = 30)

2 (33.3) 1 (16.7) 1 (16.7)

2 (50.0) 2 (50.0) 0

3 (75.0) 3 (75.0) 0

3 (75.0) 2 (50.0) 1 (25.0)

6 (100) 4 (66.7) 2 (33.3)

6 (100) 5 (83.3) 1 (16.7)

22 (73.3) 17 (56.7) 5 (16.7)

• Median time to CRS onset: 1 day (range: 1-3) • Median duration of CRS: 3 days (range: 1-10) • 9/30 (30%) of patients received tocilizumab; • 3/30 (10%) received steroids for CRS • No permanent treatment discontinuations, dose interruptions, or dose reductions due to CRS Bahlis. ASCO 2021. Abstr 8006.

Other Bi-specific T-cell engagers/ Antibodies (BiTEs) Trials in RRMM

Cancer Support Community Patient Experience Survey: Myeloma Patient Beliefs about Cancer Clinical Trials % Agree or Strongly Agree

Uncomfortable with being randomly assigned

2.63

59%

Fear receiving a placebo

2.36

55%

Fear side effects

2.34

52%

Health insurance wouldn't cover it

1.81

21%

Unable to fulfill trial requirements

1.51

22%

No clinical trials available in my community

1.48

21%

Mistrust of medical establishment ("guinea pig")

1.35

13%

Don't understand what CCT are

0.89

8%

• 52% received information about Cancer Clinical Trial.

• 35% of registrants were unsure if a Cancer Clinical Trial was available for them.

0

Strongly Disagree

1

2 Mean

3

4

Strongly Agree

What do you think about Clinical Trials?

If I enter a clinical trial, there’s a good chance that I could receive a placebo

Fact or Myth Fact: Placebos are rarely used in cancer clinical trials

What do you think about Clinical Trials?

If my doctor doesn’t mention clinical trials, it must not be right for me.

Fact or Myth

Fact: Your doctor may not be aware or that there is clinical trial for you.

What do you think about Clinical Trials?

If I enter a clinical trial, I’ll be a “guinea pig”

Fact or Myth

Fact: Clinical trials provide patients either the best treatment currently available, or a new and possibly more effective therapy

How Medical Care Advances: Clinical Trials

Standard of Clinical trial Care

Standard Care Clinicaloftrial

Standard Care Clinicaloftrial

Standard Clinicalof trial Care Standard Care Clinicalof trial Standard Clinicalof trial Care Bad

Side Effects of Therapy

Little to None

GREAT

Effectiveness of Therapy

CURE

Poor

colecrai@msu.edu

100

How to Manage Myeloma Symptoms and Side Effects

Mary Steinbach, DNP, APRN Huntsman Cancer Institute, Salt Lake City, UT, IMF Nurse Leadership Board 101

Be the Commander of Your Galactic Journey Constellation of Symptoms Mary Steinbach, FNP-C, APRN Huntsman Cancer Institute-University of Utah Regional Community Workshop October 9, 2021

You are in the Commander’s Chair Patient Education Slides 2021

Myeloma and Treatments Both Contribute to How You Feel

Constellation of Symptoms

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 10

Common Side Effects of Myeloma Drugs (page 1 of 3)

“Mides” Immunomodulatory drugs (IMIDS) Thalomid® (thalidomide)

Neuropathy (PN) Thrombosis (DVT, PE)

Revlimid® (lenalidomide)

Constellation of Symptoms

“Mibs” Proteasome Inhibitors

Pomalyst® (pomalidomide)

Velcade® (bortezomib)

Kyprolis® (carfilzomib)

*





more with dex

 more with dex

more with dex

Myelosuppression

 neutropenia

anemia, neutropenia, thrombocytopenia

 neutropenia

 thrombocytopenia

 neutropenia, thrombocytopenia

Cardiopulmonary

 slow heart rate

shortness of breath

hypotension

shortness of breath, hypertension

Fatigue, weakness

 (incl sedation)









Renal







Rash







 constipation

 diarrhea, constipation

 diarrhea, constipation

GI disturbance

Ninlaro® (ixazomib)

  thrombocytopenia

 (incl sedation)

  nausea, vomiting, diarrhea

 nausea, vomiting, diarrhea, constipation

Other *Subcutaneous administration reduces rates of PN dex = dexamethasone; DVT = deep vein thrombosis; GI = gastrointestinal PE = pulmonary embolism; PN = peripheral neuropathy Prescribing Information: thalidomide, lenalidomide, pomalidomide, bortezomib, carfilzomib, ixazomib.

 diarrhea, constipation, nausea

Common Side Effects of Myeloma Drugs (page 2 of 3)

“Mabs” Monoclonal Antibodies

Constellation of Symptoms

Monoclonal Antibody Drug Conjugate

HDAC inhibitor

SINE Compound

Farydak® (panobinostat)

Xpovio® (selinexor)

 neutropenia, thrombocytopenia

 thrombocytopenia

Darzalex® (daratumumab)

Empliciti® (elotuzumab)

Sarclisa® (Isatuximab)

Blenrep® (Belantamab Mafodotin)









neutropenia

neutropenia, thrombocytopenia

Neuropathy (PN) Infusion reaction Myelosuppression

neutropenia, thrombocytopenia

 arrythmias, ischemia

Cardiopulmonary Fatigue, weakness





 diarrhea

diarrhea, nausea





severe diarrhea, nausea, vomiting

 Anorexia, nausea, vomiting, diarrhea

Rash GI disturbance Other

diarrhea, nausea

nausea  ocular

GI = gastrointestinal; neutropenia = low white blood cell count; PN = peripheral neuropathy; thrombocytopenia = low platelets.

Prescribing Information: daratumumab, elotuzumab, isatuximab, belantamab mafodotin, panobinostat, selinexor.

 hyponatremia

Common Side Effects of Myeloma Drugs

Constellation of Symptoms

(page 3 of 3)

Anthracycline

Neuropathy (PN) Infusion reaction Myelosuppression

Doxil® (liposomal doxorubicin)

Cytoxan® NEOSAR® (cyclophosphamide)

ALKERAN® EVOMELA® (melphalan)

 Acute infusion reactions

 hypersensitivity

 hypersensitivity

 anemia, myelosuppression, immunosuppression  myocarditis, arrythmias, pneumonitis 

 severe bone marrow suppression

 neutropenia

Cardiopulmonary Fatigue, weakness GI disturbance Other

Alkylating Agents

Alkylator Conjugate

CAR-T

PEPAXTO® (melphalan flufenamide)

ABECMA® (ide-cel)

 neutropenia, thrombocytopenia, anemia

    diarrhea, nausea,  nausea, vomiting,  nausea, vomiting, vomiting, diarrhea, oral  diarrhea, nausea diarrhea constipation mucositis  rash

 rash

GI = gastrointestinal; neutropenia = low white blood cell count; PN = peripheral neuropathy; thrombocytopenia = low platelets.

Prescribing Information: doxorubicin, cyclophosphamide, melphalan.

Cytokine Release Syndrome (CRS)

Steroid Side Effects and Management Steroid Side Effects • Irritability,

mood swings, depression

• Blurred vision, cataracts • Flushing/sweating

• Difficulty sleeping

• Stomach bloating,

• Increased risk of

• Weight gain, hair

(insomnia), fatigue

infections, heart disease • Muscle weakness, cramping

hiccups, heartburn, ulcers, or gas thinning/loss, skin rashes

• Increase in blood

sugar levels, diabetes

Constellation of Symptoms

Managing Steroid Side Effects • Consistent schedule (AM vs. PM) • Take with food • Stomach discomfort: Over-the-counter or prescription medications • Medications to prevent shingles, thrush, or other infections

Steroids help kill myeloma cells.

Do not stop or adjust steroid doses without discussing it with your health care provider.

• Increase in blood pressure,

water retention

King T, Faiman B. CJON. 2017; 21(5)suppl:240-249. Faiman B, et al. CJON. 2008;12(3)suppl:53-63.

10

Fatigue, Depression, and Anxiety

Constellation of Symptoms

• All can affect quality of life and relationships • Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression

Management

• Exercise (walking, yoga, etc) • Proper rest • Support (social network, support group, professional counseling, etc) • Prayer, meditation, spiritual support • Mindfulness-based stress reduction

• • • • •

Medications Massage, aroma therapy Supplements: ginseng Transfusion, if indicated Effective management of other symptoms

At least 70% of patients experience fatigue, but only 20% tell their provider. Let your provider know about symptoms that are not well controlled or thoughts of self harm.

Catamero D et al. CJON. 2017; 21(5)suppl:7-18. Faiman, B. et al 2017.

Patient Reported Symptoms, Concerns and Provider Intervention in Patients with Multiple Myeloma.

10

Infection Prevention & Treatment • Compromised immune function comes from multiple myeloma and from treatment • Good personal hygiene (skin, oral) • Environmental control (wash hands, avoid crowds and sick people, etc) • Growth factor (Neupogen [filgrastim]) • Immunizations (NO live vaccines) • Medications (antibacterial, antiviral)

Constellation of Symptoms

Report fever of more than 100.4°F, shaking chills even without fever, dizziness, shortness of breath, low blood pressure to HCP as directed.

Infection is serious for myeloma patients!

– New research: for patients receiving active myeloma therapy, levofloxacin 500 mg once daily for 12 weeks reduced infection (fevers, death) (ASH 2017 #903)

Brigle K, et al. CJON. 2017; 21(5)suppl:60-76.

10

Deep Vein Thrombosis (DVT ) and Pulmonary Embolism (PE) • Risk Factors

Constellation of Symptoms

• Provider Management

– Personal or family history – Lifestyle (obesity, smoking, inactivity) – Medical (medications, surgery

• Symptoms – Swelling, tightness, ache/pain, change in color or temperature – Chest or shoulder pain – Shortness of breath, difficult/labored breathing – Anxiety – Rapid heart rate

– Adjusting medications and schedules (weekly steroids, types of chemo) – Prescribing blood-thinning medications according to assessed risk (aspirin, warfarin, heparin or Direct Oral Anticoagulant[DOAC]) – Anti-embolism stockings (elastic stockings)

• Self Management – Lifestyle changes (stop smoking, weight mgmt) – Activity; Moving frequently when sitting long periods; Travel precautions

Report DVT and PE symptoms immediately!

These are considered a medical emergency & require immediate care.

Noonan K, et al. CJON. 2017;21(5)suppl:37-46. Rome S, et al. CJON. 2008;12(3)suppl:21-8.

11

GI Symptoms: Prevention and Management • Diarrhea potential causes – Laxatives, antacids with magnesium – Antibiotics, antidepressants, others – Milk thistle, aloe, cayenne, saw palmetto, ginseng – Sugar substitutes in sugar free gum

• Take anti-diarrheal medication – Imodium®, Lomotil®, or Colestid if recommended – Fiber binding agents – Metamucil®, Citrucel®, Benefiber® – Welchol® if recommended

• Constipation potential causes – Opioid pain relievers, antidepressants, heart or blood pressure medications, others – Supplements: Calcium, Iron, vitamin D (rarely), vitamin B-12 deficiency

• Increase fiber – Fruits, vegetables, high fiber whole grain foods – Fiber binding agents – Metamucil®, Citrucel®, Benefiber®

Constellation of Symptoms

• Nausea potential causes – Supplements: Iron, Multi (iron-containing), others

• Management – Antiemetics, if prescribed – Frequent small meals – Avoid fatty, fried, spicy, or very sweet foods – Increase high-calorie foods to avoid weight loss

• Increase fluid intake: Avoid caffeinated, carbonated, or heavily sugared beverages; works with fiber; also good for kidneys

Discuss GI issues with health care providers to identify causes of and make adjustments to medications and supplements.

Smith LC, et al. CJON.2008;12(3)suppl:37-52. Faiman B. CJON. 2016;20(4):E100-E105.

11

Understanding Changes to Kidney/ Renal Function Risk Factors

Prevention

• Active multiple myeloma (light chains, high calcium) • Other medical issues (ex: Diabetes, dehydration, infection) • Medications (MM treatment, antibiotics, contrast dye)

• Drink, Drink, Drink • Avoid medications that can cause further kidney injury, when possible (examples: contrast dyes, NSAIDs)

Constellation of Symptoms

Treatment • Treatment for myeloma • Hydration • Dialysis

Many myeloma patients will experience kidney function problems at some point; it is important to protect your kidney function early and over time.

NSAID = non-steroidal anti-inflammatory.

Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76.

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Myeloma Cells Can Lead to Bone Damage

Constellation of Symptoms

Approximately 85% of myeloma patients develop bone disease • Protecting bone health – Nutrition – Weight-bearing activity – Medications • Vitamin D • Calcium (if approved by doctor) • Bone strengthening agents: Zometa® zoledronic acid, Aredia (pamidronate), or Xgeva® denousamab)

• Report new pain to your health care provider

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

Most myeloma patients will experience bone involvement at some point; it is important to protect your bone health

Figure 1. Bones at Highest Risk of Being Affected by Multiple Myeloma

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56.

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Peripheral Neuropathy (PN) Management • Peripheral neuropathy: damage to nerves in extremities (hands, feet, or limbs) – – – – – –

Numbness Tingling Prickling sensations Sensitivity to touch Muscle weakness Burning pain or cold sensation

Report symptoms of peripheral neuropathy early to your health care provider; nerve damage from PN can be permanent if unaddressed

Constellation of Symptoms

• Prevention / management: – Bortezomib once-weekly or subcutaneous administration – Massage area with cocoa butter regularly – Supplements: • B-complex vitamins (B1, B6, B12) • Folic acid, and/or amino acids but do not take on day of Velcade® (bortezomib) infusion – Safe environment: rugs, furnishings, shoes

• If PN worsens, your HCP may: – Change your treatment – Prescribe oral or topical pain medication – Suggest physical therapy

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Tariman, et al. CJON.2008;12(3)suppl:29-36.

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Pain Prevention and Management

Constellation of Symptoms

• Pain can significantly compromise quality of life • Sources of pain include bone disease, neuropathy and medical procedures • Management – Prevent pain when possible • Bone strengtheners to decrease fracture risk; antiviral to prevent shingles; sedation before procedures – Intervention depends on source of pain – May include medications, activity, surgical intervention, radiation therapy, etc – Complementary and integrative medicine (supplements, acupuncture, etc)

Tell your health care provider about any new bone pain or chronic pain that is not adequately controlled

Faiman B, et al. CJON. 2017;21(5)suppl:19-36.

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You are Not Alone

Questions?

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Audience Q&A with Panel

• Open the Q&A window, allowing you to ask questions to the host and panelists. They can either reply to you via text in the Q&A window or answer your question live.

• If the host answers live, you may see a notification in the Q&A window.

• If the host replies via the Q&A box – you will see a reply in the Q&A window.

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Workshop Video Replay & Slides As follow up to today's workshop, we will have the speaker slides and a video replay available.

These will be provided to you shortly after the workshop concludes.

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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.

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