Updates in Multiple Myeloma From Madrid: Data Surrounding BCMA-Directed Agents and Their Clinical Relevance

María-Victoria Mateos, MD, PhD, and Meletios Dimopoulos, MD, discuss relapsed/refractory multiple myeloma in this CE activity titled "Updates in Multiple Myeloma From Madrid: Data Surrounding BCMA-Directed Agents and Their Clinical Relevance." For the full presentation, please visit us at www.peervoice.com/HEG870.

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Updates in Multiple Myeloma From Madrid:
Data Surrounding BCMA-Directed Agents and Their Clinical Relevance

Learning Objectives

Recall safety and efficacy data from clinical trials evaluating BCMA-directed
therapies for the management of relapsed/refractory multiple myeloma

Assess the potential clinical impact of these data, including patient populations
included in trials and how these relate to real-world patients

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Part 1 of 2: Recap From Madrid 2024:
Spotlight on BCMA-Directed Therapies in RRMM

Meletios Dimopoulos, MD

Professor of Hematology-Oncology

National and Kapodistrian University of Athens
Head of the Therapeutic Department
Alexandra Hospital

Athens, Greece

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Disclosures

Meletios Dimopoulos, MD, has a financial interest/relationship or

affiliation in the form of:

Consultant for Amgen Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb

Company; Celgene Corporation; GSK plc.; Janssen Inc.; Regeneron

Pharmaceuticals, Inc.; Sanofi; Swixx Biopharma SA; Takeda Pharmaceutical
b d Company Limited; and The Menarini Group.

Advisory Board for Amgen Inc.; AstraZeneca; BeiGene; Bristol Myers

Squibb Company; Celgene Corporation; GSK plc.; Janssen Inc.; Regeneron

Pharmaceuticals, Inc.; Sanofi; Swixx Biopharma SA; Takeda Pharmaceutical

Company Limited; and The Menarini Group.

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KarMMa-2: Ide-cel for Clinical High-Risk MM

N = 31 (Cohort 2b)
Median PFS, NR
(95% Cl, 12.2-NR)

Median follow-up, 30.1 mo (range 1.0-51.4)

3 6 9 12 15 18 2 24 27 30 33 36 39 42 45 48 51
Time, mo

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CARTITUDE-4: Cilta-cel for Functionally High-Risk MM

Patients With 1 Prior LOT Patients With 1 Prior LOT and
Functionally High-Risk MM
o — Cilta-cel (n = 68) 100 n ii =
e 710%) ilta-cel (n = 40)
— SOC (n = 68) d —socin= 39)

x x
g 50 gi 50
2 2
Ca =
2 25
o o
0 3 6 9 205 B 2 24 27 0 3 6 9 nm 15 18 21 24 27

Time, mo Time, mo
Median follow-up, 15.9 mo (range, 0.1 - 27.3)

Median PFS, NR a Median PFS, NR 179

mo (85% Ci) | (NE-NE) | (mio-ne) mo (95% CI) | (800-NE) | (844-NE)
035 (019-066) 027 (012-060)

HR (95% CI) P = 0007 HR (95% CI) P=.0006

Safety Outcome | CRS: 64.7% of patients CRS: 62.5% of patients
of Note ICANS: 2.9% of patients ICANS: 5.0% of patients

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MajesTEC-1: Teclistamab for RRMM

100 Best Response
scr Mice IE D AnyGrade Grade3-4
fet
80 Safety,
ORR, 63.0% Infections 788
(104/165) ORR, 60.0% covı 2
(80/50)
æ 60 3.6 y
8 2
E
& 40
L 2CR,
20 46.1%
o
Overall RP2D Penta-Drug Refractory®

Median follow-up, 30.4 mo
*Penta-drug refractory: 22 Pls, 22 ImIDs, 21 anti-CD38 mAbs.

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MagnetisMM-3: Elranatamab for RRMM

ae

Zoo

3

3

io #9 N=123

a Median OS, 24.6 mo

8 (95% Cl, 13.4-NE)
20

Median follow-up, 28.4 mo (95% Cl, 28.0-29.0)

o 3 6 9 2 15 18 2 24 27 30 33 36 39
Time, mo

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Updates on Investigational BCMA-Directed BsAbs

Trial

(NCT) Design Outcomes
23 LOT or
Linvoseltamab | 2double- .
Pe IV once/wk (phase 1) or u
ase 1/2 Trial 17 | Gai wk 14), | triple. (phase 2) | 20% 50%
, iple- (phase 2)
KNeTOs7 e108) then once/2 wk | class— EU
refractory Infections: 74.4% (G3-4: 35.9%)
CRS: 46% (G3: 1%)
ABBV-383 January 2024
BCMA x CD3 Safety
Error BsAb 2CRS: 43% (n = 21 at 60 mg Q4W)
(NCT03933735) | 220 | monotherapy; | RRMM23LOT | ABBV-383 monotherapy at 60 mg
optimal once/4 wk will be further investigated
therapeutic in patients with RRMM who received
dose: 60 mg 22 LOT in phase 3 CARVINO trial

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DREAMM-7: BVd for RRMM

[+ BVd safety and tolerability

10
Men profile was consistent with
a known safety profiles of the
E va individual agents
à oa 2 + In the BVd and DVd arms,
E an exposure-adjusted rates of
& infections were 51.1% and
—svd 55.4% (all grades) and 22.5%
ool_—bva and 16.4% (grade 23),
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 respectively

Time, mo

+ Among all patients who
received BVd, 44% had dose
reductions, 78% had dose

366 84 delays/interruptions, and 9%
RE ee CHENE) as = any
HR (95% cl) Ue) ocular event

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DREAMM-8: BPd for RRMM

og
8 3

PFS Probability
o
ES

04
02] —ePd

— Pvd
o

caca

51% a

02468

10 12 14 16 18 20 22 24 26 28 30 32 34 36 38

Time Since Randomisation, mo

] P Pvd
MES
Median PFS, mo (95% CI) eats) eon
HR (95% Cl) | 052 037-079)

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Exposure-adjusted AE
rates were similar or lower
in BPd vs PVd arm

Ocular events were
managed by dose delays
and reductions and led to
a low rate of treatment
discontinuations (9%)

Overall rates of AEs leading

to treatment
discontinuations were low

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Abbreviations and References

KarMMa-2: Ide-cel for Clinical High-Risk MM

Abbreviation(s): CR: complete response; CRS: cytokine release syndrome; ide-cel: idecabtagene vicleucel;

NT: investigator-identified neurotoxicity; MM: multiple myeloma; NR: not reached; ORR: overall/objective response
rate; PFS: progression-free survival.

Reference(s): Leleu X et al. 29th European Hematology Association Congress (EHA 2024). Abstract $208.

CARTITUDE-4: Cilta-cel for Functionally High-Risk MM

Abbreviation(s): cilta-cel: ciltacabtagene autoleucel; ICANS: immune effector cell-associated neurotoxicity syndrome;
LOT: lines of treatment; NE: not evaluable; SOC: standard of care.
Reference(s): Weisel K et al. EHA 2024. Abstract P959.

MajesTEC-1: Teclistamab for RRMM

Abbreviation(s): ImID: immunomodulatory drug; mAb: monoclonal antibody; Pi: proteasome inhibitor; PR: partial
response; RP2D: recommended phase 2 dose; RRMM: relapsed/refractory MM; sCR: stringent CR;

VGPR: very good PR.

Reference(s): Costa LJ et al. EHA 2024. Abstract P923.

Oriol A et al. EHA 2024. Abstract P942.

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Abbreviations and References (Cont'd)

MagnetisMM-3: Elranatamab for RRMM

Abbreviation(s): OS: overall survival.
Reference(s): Mohty M et al. EHA 2024. Abstract P932.

Updates on Investigational BCMA-Directed BsAbs

Abbreviation(s): BCMA: B-cell maturation antigen; BsAb: bispecific antibody; NCT: National Clinical Trial.
Reference(s): Lentzsch S et al. EHA 2024. Abstract $212.
Weisel K et al. EHA 2024. Abstract S211.

DREAMM-7: BVd for RRMM

Abbreviation(s): BVd: belantamab mafodotin (belamaf) plus bortezomib and dexamethasone; DVd: plus bortezomib
and dexamethasone.
Reference(s): Mateos MV et al. EHA 2024. Abstract $214.

DREAMM-8: BPd for RRMM

Abbreviation(s): AE: adverse event; BPd: belamaf plus pomalidomide and dexamethasone; PVd: pomalidomide plus
bortezomib and dexamethasone.
Reference(s): Dimopoulos MA et al. EHA 2024. Abstract LB3440.

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Part 2 of 2: Placing Data Into Clinical Context:
What Will These Results Mean for Future RRMM Practice?

Maria-Victoria Mateos, MD, PhD
Associate Professor

University of Salamanca

Head of Myeloma Unit

University Hospital of Salamanca
Salamanca, Spain

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Maria-Victoria Mateos, MD, PhD, has a financial interest/relationship or
affiliation in the form of:

Speakers Bureau participant with AbbVie Inc.; Amgen Inc.; Bristol Myers
Squibb Company; Celgene Corporation; GSK plc.; Janssen Inc.; Pfizer Inc.;
Regeneron Pharmaceuticals, Inc.; and Stemline Therapeutics, Inc.
Advisory Board for AbbVie Inc.; Amgen Inc.; Bristol Myers Squibb
Company; Celgene Corporation; F. Hoffmann-La Roche Ltd.; GSK plc.;
Janssen Inc.; Kite Pharma, Inc; Oncopeptides AB (publ).; Pfizer Inc.;
Regeneron Pharmaceuticals, Inc.; Sanofi; Stemline Therapeutics, Inc.; and
Takeda Pharmaceutical Company Limited.

Speaker or Participant in Accredited CME/CPD for AbbVie Inc.; Amgen Inc.;
Bristol Myers Squibb Company; Celgene Corporation; GSK plc.; Janssen
Inc.; Pfizer Inc.; Regeneron Pharmaceuticals, Inc.; and Stemline
Therapeutics, Inc.

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BCMA-Targeted Immunotherapies in MM

CART

BiTE

payload

ADC
Cytotoxic 2

BCMA

—

MM cell death

MM cell death

Cytotoxic
cytokines

MM cell death

cD3 BCMA

Cytotoxic
cytokines

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MM Treatment Landscape

First-Line Treatment

gible i ASC’ E
+ Anti-CD38 mAb + PI + IMiD + DEX + Daratumumab-lenalidomide-DEX

+ ASCT + Daratumumab-bortezomib-melphalan-prednisone
+ LEN + Lenalidomide-bortezomib-DEX

Second-Line Treatment

Based on sensitivity/refractoriness to daratumumab and lenalidomide
+ Anti-CD38 mAb + carfilzomib-DEX + Pomalidomide-bortezomib-DEX
+ Anti-CD38 mAb + pomalidomide-DEX + Selinexor-bortezomib-DEX
+ Carfilzomib-DEX

+ Cilta-cel (approved in 2024 after 1L therapy for patients refractory to lenalidomide)

Third-Line Treatment Fourth-Line Treatment
+ Anti-CD38 mAb + pomalidomide-DEX ECMA-targeted therapy | GPRCSD-targeted therapy
+ Elotuzumab-pomalidomide-DEX CAR-Tcells BsAbs BsAbs
+ (Previous combinations, if eligible) + Ide-cel + Teclistamab + Talquetamab
TT + Cilta-cel + Elranatamab

(approved in 2024 after 2L therapy)

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BCMA-Directed Therapy: How to Select the Right Option?

Disease
Morbidity

Frailty

Age Refractory Previous Patient
dass therapies preference
Performance Renal B
status ee Cytogenetics

mily
support

The most effective regimen:
Safe and maintains QOL

7
l

Comorbidities Aggressiveness

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Selecting Between CAR-T and BsAb Therapies

CAR-Ts Bispecific Abs

+ Hospitalisation from Iymphodepletion until +10-14 d

+ Most protocols require that patients stay within 60
mins drive of the hospital

+ Weekly evaluation (or more frequent if required)

+ Neurologic and cardiac follow-up until +100 d

+ Although relevant for all patients and therapies,
CAR-T therapy requires more social support as
there are few centres in each country authorised to
deliver CAR-Ts

Days

Lymphodepletion 44 AR

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+ Hospitalisation for priming doses and until full dose
on DICI to mitigate the CRS development

+ It may be possible to administer in outpatient
facilities

+ Most BsAbs are of SC administration

+ No short follow-up is required at discharge from
hospital

+ Continuous therapy in the outpatient setting

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Real-World Data on CAR-T Cell and BsAb Therapeutic Selection

Analysis of anonymised charts from patients with MM, provided by onco-haematologists in
France, Germany, Italy, Spain, UK, USA (192 patients received CAR Ts; 210 patients received BsAbs)

Age, y «ss Mes-69 [70-74 M275 ECOG Score M3 M2 Mo:

100 100
80 80
® e

geo Eso
& 40 $40
20 20
o o

EUS us EUS us EUS us EUS: EUS us

ene? (n = 108) © = 162) (n = 48) R {= 46) (n= 60), a 38) (n= ER 162) (n= 48)
BCMA CART BCMA BiTE Ide-cel Cilta-cel BCMA BiTE

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CARTITUDE-4: Updates on ORR and MRD

soc OR (95% Ci)

Patients With 1Pı 191
Patients With 1 Prior LOT/ es = 163 (48-551)
Functionally High-Risk MM E P<.0001
2CR Odds Ratio, 44 ¿CR Odds Ratio, 33
(95% C1 21-90) (65% 0113-84) Best Response
P< 0001 P=.002
10
ee = OR 875% MM scr
ORR 79.4% (35/40) ORR 795% mice
so (54/68) Pr 75 (31/38)
5 I varr
x 60 # 60 MR
yl Fi
$ $
8 40 & És 20R,
706% 675%
20 scr Y po ace
353% 385%
o
ds zer Cita-cel soc
o Patients With 1 Prior LOT and

Functionally High-Risk MM

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Updates on ORR and MRD
MRD Negativity, % BVd Dvd
co 2CR 247 9.6
ORR, 82.7%
(95% Cl, 77.4-87.3) 2VGPR 38.7 171
80 ORR, 71.3%
(95% Cl, 65.3-76.8)
x 60
E Best Response
= _2VGPR, MB scr
65.8% mice
20 E vorr
Mier
o ll
BVd (n = 243) Dvd (n = 251)

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Abbreviations and References

BCMA-Targeted Immunotherapies in MM

Abbreviation(s): ADC: antibody-drug conjugate; BCMA: B-cell maturation antigen; BITE: bispecific T-cell engager;
CAR: chimeric antigen receptor; MM: multiple myeloma.

Reference(s): Yu B et al. J Hematol Oncol. 2020;13:125.

Rees MJ, Kumar S. Leuk Lymphoma. 2024;65:287-300.

MM Treatment Landscape

Abbreviation(s): ASCT: autologous stem-cell transplantat :
autoleucel; DEX: dexamethasone; ide-cel: idecabtagene vicleucel; Mi
mAb: monoclonal antibody; Pl: proteosome inhibitor.

Reference(s): Courtesy of Maria-Victoria Mateos, MD, PhD; June 2024.
Dimopoulos MA et al. Ann Oncol. 2021;32:309-322.

ispecific antibody; cilta-cel: ciltacabtagene
immunomodulatory drug; LEN: lenalidomide;

BCMA-Directed Therapy: How to Select the Right Option?

Abbreviation(s): QOL: quality of R-ISS: Revised International Staging System.
Reference(s): Courtesy of María-Victoria Mateos, MD, PhD; June 2024.

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Abbreviations and References (Cont'd)

Selecting Between CAR-T and BsAb Therapies

Abbreviation(s): CRS: cytokine release syndrome; DICH: day 1, cycle 1.
Reference(s): Courtesy of María-Victoria Mateos, MD, PhD; June 2024,
Yakoub-Agha | et al. Haematologica. 2020:105:297-316.

Real-World Data on CAR-T Cell and BsAb Therapeutic Selection

Abbreviation(s): ECOG: Eastern Cooperative Oncology Group.
Reference(s): Blin N et al. 29th European Hematology Association Congress (EHA 2024). Abstract P962.

CARTITUDE-4: Updates on ORR and MRD

Abbreviation(s): CR: complete response; LOT: lines of treatment; MRD: minimal residual disease; ORR: overall/objective
response rate; PR: partial response; sCR: stringent CR; SOC: standard of care; VGPR: very good PR.
Reference(s): Weisel K et al. EHA 2024. Abstract P959.

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Abbreviations and References (Cont'd)

DREAMM-7: Updates on ORR and MRD
Abbreviation(s): BVd: belantamab mafodotin (belamaf) plus bortezomib and dexamethasone;

DVd: plus bortezomib and dexamethasone.
Reference(s): Mateos MV et al. EHA 2024. Abstract S214.

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