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Therapeutic sequencing in Myeloma at relapse
Xavier Leleu
Hôpital la Milétrie, PRC, CHUInserm U1402 CIC
Laboratoire d’Immunologie Oncologie et dormance tumoralePoitiers, France
Disclosures
• Honorarium, Grants/research support, and Consulting fees:
Amgen, Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Pierre Fabre, Mundipharma, Karyopharm, Roche, Abbvie, Bristol-Myers Squibb, Gilead, Incyte
Main questions
1. Switch vs. re-treatment2. Doublet vs Triplet3. Treatment until progression
Main questions
1. Which line is best for pomalidomide2. Doublet vs Triplet3. Treatment until progression
1–3 prior lines of therapyProgressing after at least 2 lines of
therapy incl. 1 IMiD + BTZ and refractory to the last line
Lenalidomide-dexamethasoneBortezomib-dexamethasone
Pomalidomide-dexamethasone-Daratumumab-
Approved drugs in RRMM in EU until 2016
RRMM, relapsed/refractory multiple myeloma.
Lenalidomide prescribing information, available at: http://www.ema.europa.euBortezomib prescribing information, available at: http://www.ema.europa.eu
Pomalidomide prescribing information, available at: http://www.ema.europa.eu
Pomalidomide-dexamethasone
+ Cyclo or Ixa or Bort or
Dara or Elo
Daratumumab(single agent or
combination)
Clinicaltrial
At second or subsequent relapse
IMiD-based induction
PI-based doubletsKd / Vd
Bortezomib-based tripletsDaraVDPanoVDEloVDVCD
Bortezomib-based induction
Rd-based tripletsDaraRd
KRdIRdERd
Rd doublet
First relapse after
Moreau P, et al;.Ann Oncol. 2017
ESMO Guidelines 2017: RRMM
IMiDs/Lenalidomide backbone
Rd+
proteasome inhibitorCarfilzomibIxazomib
Bortezomib
Rd+
therapeutic antibodyanti-CD38 (daratumumab, isatuximab)
anti-SLAMF7 (elotuzumab)
• Triplet better by PFS median 1 to possibly 3 years +
• High risk improves
• MRD becomes a new objective
K, carfilzomib; E, elotuzumab; I, ixazomib.
1. Dimopoulos MA, et al. N Engl J Med 2016; 375:1319-13312. Stewart AK, et al. N Engl J Med. 2015;372(2):142-152.
3. Lonial S, et al. N Engl J Med. 2015;373(7):621-631.4. Dimopoulos MA, et al. Blood. 2015;126(23):Abstract 28.
5. Moreau P, et al. N Engl J Med. 2016;374(17):1621-1634.
Studies evaluating Rd-based triplets
POLLUXDRd vs Rd1
PFS HR (95% CI)
0.41 (0.31-0.53)
ORR 93%
≥ VGPR 76%
≥ CR 43%
Duration of response, mo NE
OS HR (95% CI)
0.64(0.40-1.01)
ASPIREKRd vs Rd2
ELOQUENT-2ERd vs Rd3,4
TOURMALINE-MM1
IRd vs Rd5
0.69 (0.57-0.83)
0.73 (0.60-0.89)
0.74 (0.59-0.94)
87% 79% 78%
70% 33% 48%32% 4% 14%
28.6 20.7 20.5
0.79(0.63-0.99)
0.77 (0.61-0.97) NE
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 7
Updated PFSa of POLLUX
Median follow-up: 32.9 months (range, 0-40.0 months)
Progression‐Free Survival in the ITT Population
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
100
0 3 6 9 12 15 18 42Months
30
283286
249266
206249
181238
160229
143214
126203
00
100183
No. at riskRd
DRd
21 24 36
89167
3667
111194
DRd
Rd
3927 33
516
80145
12
Median: not reached
Median: 17.5 months
HR 0.44; 95% CI, 0.34-0.55; P <0.0001
30-month PFSb
58%
35%
aExploratory analyses based on clinical cut-off date of October 23, 2017; bKaplan-Meier estimate.
Stewart AK, et al. N Engl J Med 2015; 372:142-52 Dimopoulos MA, et al. N Engl J Med 2016; 375:1319-1331
Triplet until Progression (1)
POLLUXAnti-CD38 + IMiD + Dex
Until progression
ASPIREPI + IMiD + Dex
18 months then Rd until progression
Rd(n = 396)
KRd(n = 396)
17.626.30.69 (0.57–0.83)
< 0.0001
Median PFS, moHR (KRd/Rd) (95% CI)
p value (one-sided)
0
0.2
0.6
1.0
Prop
ortio
n su
rviv
ing
with
out
prog
ress
ion
Months since randomization
0.8
0.4
0.06 18 24 30 36 42 4812
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
100
0 3 6 9 12 15 18 33Months
21 24 30
Rd (n = 283)
DRd (n = 286)
27
24-month PFS
68%
41%
HR, 0.41 (95% CI, 0.31-0.53; P <0.0001)
Median: 17.5 mo
Median not reached 24-month PFSDRd until PDK stopped
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 10
Time to MRD Negativity PFS by MRD Status (10-5)
POLLUX. Time to MRD Negativity and PFS by MRD Status
DRdMRD–
Rd MRD–
DRdMRD+
Rd MRD+
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
100
0 3 6 9 12 15 18 42Months
3021 24 36 3927 33
Rd
DRd
MR
D-n
egat
ive
patie
nts,
%
0
10
20
30
40
0 3 6 9 12 15 18 42Months
30
283286
272271
252255
242235
229208
219186
209172
00
183151
No. at riskRd
DRd
21 24 36
181153
7765
193167
3927 33
166139
2218
12
1476269210
1476235190
1476192173
1375168163
1372147157
1269131145
1269114134
0000
126688117
No. at riskRd MRD negative
DRd MRD negativeRd MRD positive
DRd MRD positve
106279105
8547291
126999125
0111
0759
6263041
PI - Imids -DexPFS by risk group
Aspire Tourmaline-MM1 Pollux
Median, months KRd Rd IRd Rd DRd Rd
High 23.1 13.9 21.4 14.7 22.6 10.2
Standard 29.6 19.5 20.6 9.7 NR 18.5
Avet-Loiseau H, et al. Blood. 2016;128:1174-80.Moreau P, et al. Blood. 2015;126:727. Presented at ASH 2015.
Moreau P, et al. N Engl J Med. 2016;374:1621-34.Weisel K, et al. Presented at ASCO 2017
Prolonged PFS in ASPIRESurvie sans progression chez
les patients en rechute précoce
Progression/décès, n (%)SSP médiane, moisHR (KRd/Rd) (IC à 95 %)Valeur p (test unilatéral)
KRd (n = 113)70 (61,9 %)
21,4
Rd (n = 104)64 (61,5 %)
10,7
0,714 (0,508, 1,004)0,0257
Nombre à risque :KRdRd
Pro
porti
on e
n su
rvie
sa
ns p
rogr
essi
on1,0
0,8
0,6
0,4
0,2
0,00 6 12 18 24 30 36 42
Mois depuis la randomisation113104
8661
7238
5531
4322
2117
77
KRd
Rd
Progression/décès, n (%)SSP médiane, moisHR (KRd/Rd) (IC à 95 %)Valeur p (test unilatéral)
KRd (n = 263)130 (49,4 %)
29,7
Rd (n = 257)150 (56,2 %)
18,2
0,675 (0,533, 0,854)0,0005
Nombre à risque :KRdRd
Pro
porti
on e
n su
rvie
sa
ns p
rogr
essi
on
1,0
0,8
0,6
0,4
0,2
0,0
Survie sans progression chez les patients en rechute tardive
0 6 12 18 24 30 36 48Mois depuis la randomisation
263267
228204
195149
157110
12787
8549
1510
42
11
KRd
Rd
EARLY
LATE
Weisel K et al., ASCO 2017
**P = 0.0009. ***P = 0.0001. aPercentage of patients within a given risk group and treatment arm.
21
32
0
12
0
5
10
15
20
25
30
35
High risk Standard risk
MR
D-n
egat
ive
patie
nts
per r
isk
grou
p, %
a
** ***
DRdn = 28
Rdn = 37
DRdn = 133
Rdn = 113
MRD-negative rates PFS in high-risk patients
% s
urvi
ving
with
out p
rogr
essi
on0
20
40
60
80
100
0 3 6 9 12 15 18 33Months
21 24
Rd MRD positive
DRd MRD negative
27
DRd MRD positive
30
In POLLUX, high-risk patients treated with daratumumab achieve MRD negativity and remain progression free
ClinicalTrials.gov Identifiers: NCT02136134
POLLUX: MRD by Cytogenetic Risk Status (10–5)
CR, complete response; DOR, duration of response; MPT, melphalan-prednisone-thalidomide; PR, partial response; Rd, lenalidomide and low-dose dexamethasone; Rd18, Rd for 18 cycles; VGPR, very good partial response. Bahlis N et al. Presented at EHA 2015
Rd (FIRST): Impact of depth of response on duration of response
• Median DOR was prolonged with Rd continuous
• vs Rd18 or MPT
PI-dex backbone
PI-dex+
LenalidomidePomalidomide
PI-dex+
Therapeutic antibodyanti-CD38 (daratumumab, isaruximab…)
anti-SLAMF7 (elotuzumab)
• Triplet does better by PFS median 1–x years
• High risk improves
• MRD becomes a new objective
Historically• Used upfront• Not optimal, as re-treatment
2017• Lenalidomide moves upfront• Novel combination
1. Palumbo et al. Presented at ASCO 2016 (Abstract LBA4)2. Dimopoulos MA, et al. Lancet Oncol. 2016;17(1):27-38.
3. San-Miguel JF, et al. Lancet Oncol. 2014;15(11):1195-1206.4. San-Miguel JF, et al. Blood. 2015;126(23):Abstract 3026.
5. Jakubowiak A, et al. Blood. 2016. Epub ahead of print.
Efficacy of PI-based triplets
DaratumumabDVd vs Vd1
PFS HR (95% CI) 0.39 (0.28-0.53)
PFS median, mo NE
VGPR 59%
CR 19%
Duration of response,mo NE
OS HR (95% CI) 0.77 (0.47, 1.26)
CarfilzomibKd vs Vd2
PanobinostatPVd vs Vd3,4
ElotuzumabEVd vs Vd5
0.53 (0.44-0.65) 0.63 (0.52-0.76) 0.72 (0.59-0.88)
18.7 12.0 9.7
54% 28% 36%
13% 11% 4%
21.3 13.1 11.4
0.79 (0.58-1.08) 0.94 (0.78-1.14) 0.61 (0.32-1.15)
CASTOR: 1-Year Update
Weisel K et al., ASCO 2917
SOC, standard of care.aExploratory analyses based on 1-year update: clinical cut-off date of January 11, 2017. 1. Lentzsch S, et al. Poster presentation at ASCO 2017. Abstract 8036.
18-month PFSa
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
0 3 6 9 12 15 18 30Months
21 24 27
Median 16.7 moDVd (n = 251)
Vd (n = 247)Median 7.1 mo
48%
8%HR: 0.31 (95% CI, 0.24-0.39; P <0.0001)
100
Adding daratumumab to SOC regimens significantly prolongs PFS
• Median follow-up of 19.4 months
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
100
0 3 6 9 12 15 18 27Months
21 24
Vd MRD positive
DVd MRD negative
DVd MRD positive
PFS in high-risk patients
Median follow‐up : 12 months
Dimopoulos et al. Lancet Oncol 2016
Btz Dex versus Kd (ENDEAVOR trial)
Dimopoulos et al. Lancet Oncol 2017
Median follow‐up : 3 yearsmedian OS : 40 (Vd) vs 47 (Kd)
months
Btz Dex versus Kd (ENDEAVOR trial)
IMiD/PI grey zone
IMiD-based PI-based
IMiD-basedPI-based
Re-treatment• Relapsed not refractory• Long PFS/DoR• Safety
Reuse upfront regimenlikely in a triplet-based combo
Example:VMP x9/12 / W§W: PFS of 4 yearsRd x24 / W§W: PFS of 4 years
Why not re-treatment?Why not VRd?
Module 2 Part 2 data: Scenario C: Retreat with LEN (6/13)
20.6 20.6
14.7
17.5
13.9
0
5
10
15
20
25
30
Overall population Prior LEN No prior LEN
Med
ian
PFS,
mos
Rd+I RdPrior LEN: 12%
LEN refractory: not eligible
360 16362 318n
Mateos M-V, et al. Presented at ASCO 2016:abstr 8039;Moreau P, et al. N Engl J Med. 2016;374:1621–1634.
TOURMALINE-MM1 IRd in patients who received prior LEN
4444 316
NE
0.74 (0.59–0.94) 0.58
(0.28–1.23)
HR (95% CI)0.77
(0.60–1.00)
Prior LEN exposure was permitted if:
• NOT refractory to prior LEN therapy (refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of LEN)
Stewart AK, et al. N Engl J Med 2015; 372:142-52 Dimopoulos MA, et al. N Engl J Med 2016; 375:1319-1331
Triplet until Progression (2)
POLLUXAnti-CD38 + IMiD + Dex
Until progression
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
100
0 3 6 9 12 15 18 33Months
21 24 30
Rd (n = 283)
DRd (n = 286)
27
24-month PFS
68%
41%
HR, 0.41 (95% CI, 0.31-0.53; P <0.0001)
Median: 17.5 mo
Median not reached
18-month PFSa
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
0 3 6 9 12 15 18 30Months
21 24 27
Median 16.7 moDVd (n = 251)
Vd (n = 247)Median 7.1 mo
48%
8%HR: 0.31 (95% CI, 0.24-0.39; P <0.0001)
100
CASTORAnti-CD38 + PI + Dex
DARA Until progression
DRd until PD
D until PD
Current and future treatment options in RRMM
Pd/Nivolumab +/-Elotuzumab
Pd/Nivolumab +/-Elotuzumab
Pomalidomide regimens
PVdPVd
Pd/IsatuximabPd/Isatuximab
Pd/PembrolizumabPd/Pembrolizumab
Pd/DaratumumabPd/Daratumumab
KRdKRd
ERdERd
IRdIRd
DRdDRd
DVdDVd
Lenalidomide regimens PI regimens
Venetoclax/VdVenetoclax/Vd
Selinexor/VdSelinexor/VdKdKd
Pd/OprozomibPd/Oprozomib
3rd line +2nd line +
OPTIMISMM (MM007) STUDY DESIGN: Ongoing
(n = 391)POM+BTZ+DEX (PVd) 21
day-cycle until PD or unacceptable
toxicity
RA
ND
OM
IZA
TIO
N (n
=782
) 1:
1
Follow-Up for OS , MM tx, SPM
5 years post last randomization(n = 391)
BTZ+DEX (Vd) 21 day-cycle until PD or
unacceptable toxicity
Tx D/Cprior to PD
Tx D/C due to PDOngoing
evaluationEvery 21(± 3) days
PFS follow-upEvery 21 (± 3) days
PDStratification•Age (≤ 75 vs. > 75 yrs)
•Number of prior anti-MM regimens ( 1 vs. > 1)
•β2M at screening (< 3.5 mg/L vs. ≥ 3.5 mg/L ; ≤ 5.5 mg/L vs. > 5.5 mg/L)
Bortezomib = Velcade™, D/C: discontinuation, PD: progressive disease
A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide, Bortezomib and Low-Dose Dexamethasone versus Bortezomib and Low-Dose Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma
1-3 prior linesNo refractary to bortezomib
Fresh biopsyFresh biopsy
Patient encounter
Genomicprofiling
Data interpretation
Management decision
Clinical response?
Drug resistance?
Salvage or new therapy?
What is precision cancer medicine?
• A large proportion of cancers may contain at least one plausibly actionable genetic alteration
• Therapies designed to target the molecular alteration (BRAF) or pathways that aid cancer development
975. Venetoclax Combined with Bortezomib and Dexamethasone for Patients with Relapsed/Refractory Multiple Myeloma
Philippe Moreau, Asher A. Chanan‐Khan, Andrew W. Roberts, Amit B. Agarwal, Thierry Facon, Shaji Kumar, CyrilleTouzeau, Jaclyn Cordero, Jeremy Ross, Wijith Munasinghe, Jia Jia, Ahmed H. Salem, Joel Leverson, Paulo Maciag, Maria Verdugo, and Simon J. Harrison
Monday, December 5, 2016, 3:15 PM
Venetoclax* with bortezomib + dexamethasone for RRMM: Open-label Phase 1b study
Objectives: Assessment of safety, pharmacokinetics, maximum tolerated dose, recommended phase 2 dose, and efficacy (ORR, time to progression, and duration of response) of the combination therapy in RRMM
RRMM
Dose escalation (N=54)
Venetoclax50–1200 mg per dose cohort
BortezomibDexamethasone
Dose escalation (N=54)
Venetoclax50–1200 mg per dose cohort
BortezomibDexamethasone
RRMMpatients
Safety expansion (N=12)
Venetoclax800 mg
BortezomibDexamethasone
Safety expansion (N=12)
Venetoclax800 mg
BortezomibDexamethasone
Patient characteristics Venetoclax (N=66)
Median age, years 64
ISS stage II/III, n (%) 39 (59)
Median number of prior therapies, n (range)Bortezomib refractory, n (%)Lenalidomide refractory, n (%)
3 (1–13)21 (32)37 (56)
Prior ASCT, n (%) 41 (62)
* Potent and selective, orally bioavailable small-molecule inhibitor of BCL-2.ASCT, autologous stem cell transplant; ISS, International Staging System; ORR, overall response rate; RRMM, relapsed or refractory multiple myeloma.Moreau P, et al. 58th American Society of Hematology Annual Meeting 2016, Abstract 975.
28 3219 26 35
20 26
2332
5
34 15 3612
18 20
5
235
7 9 10
0
20
40
60
80
100
Pat
ient
s (%
)
PR VGPR CR sCR
Venetoclax+bortezomib+dexamethasone efficacy response rates in RRMM
* Numbers are based on evaluable patients per subgroup.CR, complete response; DoR, duration of response; ORR, overall response rate; PR, partial response; RRMM, relapsed or refractory multiple myeloma; sCR,stringent complete response; TTP, time to progression; VGPR, very good partial response.Moreau P, et al. 58th American Society of Hematology Annual Meeting 2016, Abstract 975.
RRMM
DoR in months
TTP in months
All patients (n=65)
8.8 8.6
Bortezomib refractory and 1-3 prior therapies (n=31)
10.6 11.3
Bortezomibnaïve and 1-3 prior therapies
15.8 17.1
• Response rates were higher in patients non-refractory to bortezomib and/or with 1–3 prior therapies (ORR 89–94%) compared to all patients
• In patients non-refractory to prior bortezomib but refractory to lenalidomide, the ORR was 86% compared with 91% in those who were non-refractory to lenalidomide
• Clinical responses were comparable in patients with t(11;14) MM (ORR 78%) and without t(11;14) MM (ORR 66%)
• Median follow-up: 4.9 months
ORR for patients with RRMM*
ORR 68%
ORR 89%
ORR 24%
ORR 89%
ORR 55%
ORR 20%
ORR 94%
All evaluable patients (N=65)
Bortezomib non-refractory and
1-3 prior therapies (n=31)
Bortezomib Prior therapiesNon-refractory
(n=44)Refractory
(n=21)1-3
(n=35)4-6
(n=20)>6
(n=10)
Harnessing the immune system to fight myeloma
ADCC, antibody-dependent cellular cytotoxicity;ADCP, antibody-dependent cellular phagocytosis;
CDC, complement-dependent cytotoxicity;WBC, white blood cell.Rodríguez-Otero P, et al. Haematologica 2016;102:423–32.
Monoclonal antibodies CAR-T cells Therapeutic vaccines
• Direct effects
• CDC
• ADCC
• ADCP
• Effector cell engagement
1. Extract WBCs
2. Modify and expand cells ex vivo
3. Infuse MM-targeted cells back into patient
Passive Active
CD138
CD20
CD40
CD56
CD38
CS1
IGF1-R
Il-6
Plasmocyte
Monoclonal antibodies in multiple myelomaTargets ?
- Rituximab
- Lucatumumab : Humanized Anti CD40
- Lorvotuzumab: Humanized Anti CD56 + maytansine
- AVE1642: Humanized Anti IGF1-R (CD221)
- BT062: Chimeric Anti CD138 + maytansine
- RadioimmunotherapyAnti CD138 conjugated with 213Bi
- Siltuximab: Chimeric Anti Il-6
Daratumumab: Mechanisms of Action• CD38 is highly and ubiquitously expressed on myeloma cells1,2
• DARA is a human IgG1 monoclonal antibody that binds CD38-expressing cells
• DARA binding to CD38 induces tumor cell death through direct and indirect mechanisms3-5
Immunomodulation
Adenosine
cADPRADPRNAADP
Ca2+
NAD
CD8+
T cell
CD38
MM cellCD38
DARA
NK cellMacrophageComplement
CD38
MDSC
Immune-mediated activity
Directanti-tumor
effect
ADPC ADCCCDC
MM cell
Adenosine
AMPCa2+
Ca2+
Ca2+
B reg
CD38+
T reg
DARA
Tumor celldeath
DARA
CD38
Apo
ptos
is v
ia
cros
s-lin
king
CD
38 e
nzym
atic
in
hibi
tion
Dec
reas
ed
imm
unos
uppr
essi
on
1. Lin P, et al. Am J Clin Pathol. 2004;121(4):482-488.2. Santonocito AM, et al. Leuk Res. 2004;28(5):469-477.3. de Weers M, et al. J Immunol. 2011;186(3):1840-1848.4. Overdijk MB, et al. MAbs. 2015;7(2):311-321.5. Krejcik J, et al. Presented at: 57th ASH Annual
Meeting; December 5-8, 2015; Orlando, FL. Abstract 3037.
33
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).
Daratumumab Monotherapy for Patients With Intermediate or High‐risk Smoldering Multiple Myeloma (SMM):
CENTAURUS, a Randomized, Open‐Label, Multicenter Phase 2 Study
Craig C. Hofmeister, Ajai Chari, Yael C. Cohen, Andrew Spencer, Peter Voorhees, Jane Estell, Christopher Venner, Irwindeep Sandhu,Matthew Jenner, Catherine Williams, Michele Cavo, Niels
W.C.J. van de Donk, Meral Beksac, Steven Kuppens, Rajesh Bandekar, Tobias Neff, Christoph Heuck, Ming Qi, Hartmut Goldschmidt, C. Ola Landgren
Oral presentationSession Name: Myeloma: Therapy, Excluding Transplantation: Immunotherapy in Myeloma and AmyloidSession Date: Sunday, 10 December 2017 Session Time: 4:30 – 6:00PM
Presenter: Tobias Neff, MD
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 35
Scre
enin
g
1:1:
1 R
AN
DO
MIZ
ATI
ON Cycle 1:
QWCycles 2 & 3:
Q2WCycles 4-7:
Q4WCycles 8-20:
Q8W
Cycle 1: QW
Cycles 2-20: Q8W
n = 41
n = 41
n = 41
Arm A (16 mg/kg IV; 8-week cycles); Long Intense (max 3 years)
Arm B (16 mg/kg IV; 8-week cycles); Intermediate (max 3 years)
Arm C (16 mg/kg IV; one 8-week cycle); Short Intense
Following until PD or end of study
(4 years from LPFD)
Primary endpoints:• CR• % patients with PDa
or death per patient-yearCycle 1:
QW
1. Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-e548.
CENTAURUS Study Design
aAs defined by 2014 IMWG criteria for smoldering multiple myeloma.
• CR rate: proportion of subjects who achieve a CR in each arm– First assessed 6 months after last patient randomized
• PD/death rate: ratio of subjects with an event (PD or death) to the total follow-up for all patients– Assessed 12 months after last patient randomized– Disease progression to MM assessed according to IMWG guidelines1
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 36
Progression-Free Survival
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
100
0 3 6 9 12 15 18 24Months
21
Arm B: IntermediateArm A: Long intense
Arm C: Short intense
414141
414140
403635
393631
373224
211916
1286
000
111
No. at riskLong intenseIntermediate
Short intense Post-hoc analysis comparing Arm A + Arm B versus
Arm C: P value = 0.0398
Extended Daratumumab Therapy Prolongs PFS
Study arm 12-month PFS rate
Progression to MM based on SLiMCRABcriteria, n
Arm ALong Intense 95% 3
Arm BIntermediate 88% 5
Arm CShort Intense 81% 9
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).
Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D‐VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for
Transplant (ALCYONE)
Maria Victoria Mateos, Meletios A. Dimopoulos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook,
Sebastian Grosicki, Andre Crepaldi, Anne Marina Liberati, Philip Campbell, Tatiana Shelekhova, Sung‐Soo Yoon,Genadi Iosava, Tomoaki Fujisaki,Mamta Garg, Christopher Chiu, Jianping Wang,
Robin Carson, Wendy Crist, William Deraedt, Marie Nguyen, Ming Qi, Jesus San‐Miguel
Oral presentationSession Name: Late‐Breaking AbstractsSession Date: Tuesday, 12 December 2017 Session Time: 7:30 AM – 9:00 AM
Presenter: Marie Nguyen, MD
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 39
ALCYONE Study Design
Key eligibility criteria:
• Transplant-ineligible NDMM
• ECOG 0-2• Creatinine
clearance ≥40 mL/min
• No peripheral neuropathy grade ≥2
Stratification factors• ISS (I vs II vs III)• Region (EU vs other)• Age (<75 vs ≥75 years)
1:1
Ran
dom
izat
ion
(N =
706
)
D-VMP × 9 cycles (n = 350)
Daratumumab: 16 mg/kg IVCycle 1: once weeklyCycles 2-9: every 3 weeks
+
Same VMP schedule
Follow-up for PD and
survival
Primary endpoint:• PFS
Secondary endpoints:• ORR• ≥VGPR rate• ≥CR rate• MRD (NGS; 10–5)• OS• Safety
VMP × 9 cycles (n = 356)Bortezomib: 1.3 mg/m2 SC
Cycle 1: twice weeklyCycles 2-9: once weekly
Melphalan: 9 mg/m2 PO on Days 1-4 Prednisone: 60 mg/m2 PO on Days 1-4
DCycles 10+
16 mg/kg IV
Every4 weeks: until PD
Statistical analyses• 360 PFS events: 85% power for
8-month PFS improvement• Interim analysis: ~216 PFS events
• Cycles 1-9: 6-week cycles• Cycles 10+: 4-week cycles
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 40
% s
urvi
ving
with
out p
rogr
essi
on
0
20
40
60
80
0 3 6 9 12 15 18 27Months
356350
303322
276312
261298
231285
127179
6193
00
210
No. at riskVMP
D-VMP
21 24
1835
12-monthPFSa
18-monthPFSa
HR, 0.50 (95% CI, 0.38-0.65; P <0.0001)
VMPMedian: 18.1 months
D-VMPMedian: not reached
87%
72%
76%
50%
100
Pre-specified interim analysis after 231 PFS events Median (range) follow-up: 16.5 (0.1-28.1) months
PFS
aKaplan-Meier estimate.
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 42
6
22
0
5
10
15
20
25
VMP (n = 356) D-VMP (n = 350)
MR
D-n
egat
ive
rate
, %
P <0.00013.6X
% s
urvi
ving
with
out p
rogr
essi
on0
20
40
60
80
100
0 3 6 9 12 15 18 27Months
2278
334272
2278
281244
2278
254234
2277
239221
2175
210210
1458
113121
8315362
0000
0228
No. at riskVMP MRD negative
D-VMP MRD negativeVMP MRD positive
D-VMP MRD positive
21 24
4141421
VMP MRD negative
VMP MRD positive
D-VMP MRD negativeD-VMP MRD positive
MRD‐negative Rates and PFS by MRD Status
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).
Interim Safety Analysis of a Phase 2 Randomized Study of Daratumumab (Dara), Lenalidomide (R), Bortezomib (V), and Dexamethasone (d; Dara‐Rvd) Vs. Rvd in Patients (Pts) With Newly Diagnosed Multiple Myeloma (MM) Eligible for High‐
Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT)
Peter M. Voorhees, Brandi Reeves, Nitya Nathwani, Cesar Rodriguez, Yana Lutska, Laura Hydutsky, Huiling Pei, Jon Ukropec, Ming Qi, Thomas Lin, Luciano J. Costa
Poster presentationSession Name: Myeloma: Therapy, Excluding Transplantation: Poster ISession Date: Saturday, 9 December 2017 Session Time: 5:30 – 7:30PM
Presenter: Daniela Hoehn, MD, PhD
Cassiopeia IFM/Hovon
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).
Daratumumab (DARA) in Combination with Carfilzomib, Lenalidomide, and Dexamethasone (KRd) in Patients With Newly Diagnosed Multiple Myeloma (MMY1001): Updated
Results From an Open‐label, Phase 1b Study
Ajai Chari, Saad Z. Usmani, Amrita Krishnan, Sagar Lonial, Raymond L. Comenzo, Kaida Wu, JianpingWang, Parul Doshi, Brendan Weiss, Jordan M. Schecter, Andrzej Jakubowiak
Poster presentationSession Name: Myeloma: Therapy Excluding Transplantation: Poster IISession Date: Sunday, 10 December 2017 Session Time: 6:00 – 8:00PM
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 46
MMY1001: DARA Kd Study Design
EndpointsPrimary• Safety, tolerabilitySecondary• ORR, duration of CR,
duration of response, overall survival
Dosing Schedule (28-d cycles)Daratumumab• Single dose: 16 mg/kg QW on Cycles 1-2, Q2W on
Cycles 3-6, and Q4W thereafter (n = 10)• Split dose: 8 mg/kg on Days 1-2 of Cycle 1 and 16
mg/kg QW on Cycle 2, Q2W on Cycles 3-6, and Q4W thereafter
Carfilzomib• 20 mg/m2 Cycle 1 Day 1• Escalated to 70 mg/m2 Cycle 1 Day 8+; weekly (Days 1,
8, 15)Dexamethasone: 40 mg/weeka
Eligibility/Treatment• Relapsed MM• 1-3 prior LOTs
including bortezomiband an IMiD
• Carfilzomib-naive• ECOG score ≤2• LVEF ≥40%• ANC ≥1 x 109/L• Platelet count ≥75 x
109/L
a20 mg if >75 years of age. On DARA dosing days, dexamethasone 20 mg IV was administered as premedication on infusion day and 20 mg PO the day after infusion; for DARA as a split first dose, dexamethasone 20 mg IV was administered as a premedication on Cycle 1 Day 1 and Cycle 1 Day 2; on Cycle 1 Day 3, administration of low-dose methylprednisolone (≤20 mg PO) was optional. On weeks when no DARA infusion was administered, dexamethasone was given as a single dose on Day 1; if dexamethasone was reduced to 20 mg, methylprednisolone (≤20 mg PO) was administered the day after DARA infusion to prevent delayed IRRs. Montelukast was required before first DARA dose and was optional for subsequent doses.
Open-label, nonrandomized, multicenter, phase 1b study
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 51
ORR MRD-negative Rates in All Treated Pts
ORR and MRD‐negative Rates
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).
PFS: All Patients and Len‐refractory Patients
52
All Treated Patients
Lenalidomide-refractory Patients
Phase 1b Study of Daratumumab Plus Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple
Myeloma (RRMM) With ≥2 Prior Lines of Therapy
Ajai Chari,1 Attaya Suvannasankha,2 Joseph W. Fay,3 Bertrand Arnulf,4 Jonathan Kaufman,5 Jainulabdeen J. Ifthikharuddin,6 Brendan Weiss,7 Amrita Krishnan,8
Suzanne Lentzsch,9 Raymond Comenzo,10 Jianping Wang,11 Tara Masterson,12
Kerri Nottage,11 Jordan Schecter,11 Christopher Chiu,12 Nushmia Khokhar,12
Tahamtan Ahmadi,12 Sagar Lonial5
ClinicalTrials.gov Identifier: NCT01998971
1Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA; 2Indiana University School of Medicine and Simon Cancer Center, Richard L. Roudebush VAMC, Indianapolis, IN, USA; 3Baylor Institute for Immunology Research, Dallas, TX, USA; 4Hôpital Saint Louis, Paris, France; 5Department of
Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA; 6James P. Wilmot Cancer Center, University of Rochester Strong Memorial Hospital,
Rochester, NY, USA; 7Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 8The Judy and Bernard Briskin Myeloma
Center, City of Hope, Duarte, CA, USA; 9Columbia University Medical Center, New York, NY, USA; 10Division of Hematology-Oncology, Tufts Medical Center, Boston, MA, USA;
11Janssen Research & Development, Raritan, NJ, USA; 12Janssen Research & Development, Spring House, PA, USA.
18
25
9
8
0
10
20
30
40
50
60
70
DARA + POM-D (N =103)
OR
R, %
PR VGPR
CR sCR
ORRa: DARA + POM-D
54
DARA + POM-D(N = 103)
n (%) 95% CIORR(sCR+CR+VGPR+PR) 62 (60) 50.1-69.7
Best responsesCRCRVGPRPRMRSDPDNE
8 (8)9 (9)
26 (25)19 (18)2 (2)
26 (25)3 (3)
10 (10)
3.4-14.74.1-15.917.2-34.811.5-27.30.2-6.8
17.2-34.80.6-8.34.8-17.1
VGPR or better (sCR+CR+VGPR) 43 (42) 32.1-51.9
CR or better (sCR+CR) 17 (17) 9.9-25.1
ORR = 60%
42%VGPR
or better
17%CR or better
aBased on independent safety monitoring board assessment. Daratumumab IFE reflex assay was used to mitigate DARA-mediated interference with assessment of CR
Among patients with CR or better, the minimal residual disease negative rate at:– 10–4 threshold = 6/17 (35%)
– 10–5 threshold = 5/17 (29%)
– 10–6 threshold = 1/17 (6%)
Deep responses were observed with DARA + POM-D
OS: DARA + POM-D
12-month OS rate: 66.2% (95% CI, 55.6-74.8)
55Patients with SD/MR derive survival benefit with DARA
+ POM-D
% s
urvi
ving
pat
ient
s
0
20
40
60
80
100
0 3 6 9 12 15 18 27
No. at risk
Months
21 24
103 88 75 63 49 18 5 03 2
NE, not evaluable.
% s
urvi
ving
pat
ient
s0
20
40
60
80
100
0 3 6 9 12 15 18 27
622813
62224
59151
52110
4360
1710
410
110
≥PRSD/MRPD/NE
No. at risk Months
≥PR SD/MR
24
000
PD/NE
21
210
Median: 17.5 months (95% CI, 13.3-NE)
Median: NE (95% CI, 17.5-NE)
Median: 8.5 months (95% CI, 5.0-12.3)Median: 2.3
months (95% CI, 0.6-5.4)
OS OS by Response Category
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).
Subcutaneous Delivery of Daratumumab in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM): PAVO, an
Open‐label, Multicenter, Dose Escalation Phase 1b Study
Ajai Chari, Hareth Nahi, Maria‐Victoria Mateos, Henk Lokhorst, Jonathan L. Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Peter Hellemans, Tara Masterson, Pamela
L. Clemens, Kevin Liu, Jesus San‐Miguel, Saad Z. Usmani
Oral presentationSession Name: Myeloma: Therapy, Excluding Transplantation: Studies in Relapsed and Refractory Multiple MyelomaSession Date: Monday, 11 December 2017 Session Time: 4:30 – 6:00PM
Presenter: Jordan Schecter, MD
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 57
PAVO Study Design
PAVO, an Open‐label, Multicenter, Dose Escalation Phase 1b Study
Key eligibility criteria • RRMM with measurable disease
• ≥2 prior lines of treatment
• Not received anti‐CD38 therapy
aGroup 2 comprises 4 distinct cohorts, each treated with DARA 1,800 mg and rHuPH20 45,000 U. Ctrough on Cycle 3/Day 1 in Group 1 supported dose selection for Group 2. The study evaluation team reviewed safety after Cycle 1 and PK after Cycle 3/Day 1 for each group.bAdministered 1 hour prior to infusion. c100 mg for the first and second infusions; dose may be reduced to 60 mg thereafter.
Group 1 (n = 8)DARA‐MD: 1,200 mgrHuPH20: 30,000 U
Group 2a (n = 45)DARA‐MD: 1,800 mgrHuPH20: 45,000 U
Dosing schedule Approved schedule for IV 1 Cycle = 28 days
Group 3 (n = 25)DARA‐SC: 1,800 mgrHuPH20: 30,000 U
Part 1: mixed
formulation
Part 2: concentrated co-
formulation
Primary endpoints• Ctrough of DARA at Cycle 3/Day1
• SafetySecondary endpoints• ORR• CR• Duration of response• Time to response
Pre-b/post-infusion medication• Acetaminophen• Diphenhydramine• Montelukast• Methylprednisolonec
Infusion time• DARA-MD 1,200 mg: 20-min (60 mL)• DARA-MD 1,800 mg: 30-min (90 mL)• DARA-SC 1,800 mg: 3-5 min (15 mL)
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 58
Pharmacokinetics Findings
Nominal time after first dose (hours)
First dose Last weekly dose (8th dose)
Max CtroughDA
RA
con
cent
ratio
n (µ
g/m
L)
0
500
1000
2 24 72 168 (7 days)10
1,200 mg MD 1,800 mg MD16 mg/kg IVa 1,800 mg SC
Nominal time after last QW dose (hours)
DA
RA
con
cent
ratio
n (µ
g/m
L)
0
200
100
300
2 24 72 168 (7 days)10 12 48
400 1500
aFrom study GEN501.
INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 59
DARA-SC 1,800 mg(n = 25)
OR
Ra
(%)
DARA-MD 1,800 mg(n = 45)
≥VGPR: 28%
42%38%
44%
≥VGPR: 20%
4.3 monthsb 8.3 months 4.6 monthsMedian follow-up:
≥VGPR: 9%
Response Rates
aResponse-evaluable set; bData presented by Usmani SZ, et al. 58th Annual Meeting and Exposition of the American Society of Hematology. Abstract: 1149.
ELOQUENT-2 Study Design • Open-label, international, randomized, multicenter, phase 3 trial (168 global sites)
• Endpoints:– Co-primary: PFS and ORR– Other: overall survival (data not yet mature); duration of response, quality of life, safety
• All patients received premedication to mitigate infusion reactions prior to Elo administration
Key inclusion criteria
•RRMM•1–3 prior lines of therapy
•Prior Len exposure permitted in 10% of study population (patients not refractory to Len)
Elo plus Len/Dex (E-Ld) schedule (n=321)
Elo (10 mg/kg IV): Cycle 1 and 2: weekly; Cycles 3+: every other weekLen (25 mg PO): days 1–21
Dex: weekly equivalent, 40 mg
Elo plus Len/Dex (E-Ld) schedule (n=321)
Elo (10 mg/kg IV): Cycle 1 and 2: weekly; Cycles 3+: every other weekLen (25 mg PO): days 1–21
Dex: weekly equivalent, 40 mg
Len/Dex (Ld) schedule (n=325)Len (25 mg PO): days 1–21;
Dex: 40 mg PO days 1, 8, 15, 22
Len/Dex (Ld) schedule (n=325)Len (25 mg PO): days 1–21;
Dex: 40 mg PO days 1, 8, 15, 22
Repeat every 28 days
Assessment
•Tumor response: every 4 wks until progressive disease•Survival: every 12 wks after disease progression
ELOQUENT-2: Extended 4 years follow-up
Isatuximab
CD38
ISATUXIMAB TCD1407
A Phase Ib Study of Isatuximab plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma
(RRMM)
Joseph Mikhael,1 Paul Richardson,2 Saad Usmani,3Noopur Raje,4 William Bensinger,5 Dheepak Kanagavel,6
Lei Gao,7 Samira Ziti-Ljajic,6 Kenneth Anderson2
1Mayo Clinic, Phoenix, AZ, USA; 2Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 3Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC, USA; 4Massachusetts
General Hospital, Boston, MA, USA; 5Swedish Cancer Institute, Seattle, WA, USA; 6Sanofi R&D, Vitry-Alfortville, France; 7Sanofi Oncology, Cambridge, MA, USA
symptomatic MM 1st line treatment
18-70a
4 x VRD
2 x VRD consolidation
Cy + G-CSF + leukapheresis
4 x VRD + Elotuzumab
HDM + TPL
2. HDM + TPL (if no nCR/CR)
Rev. MT
Randomization
A-I A-II B-I B-II
A-I + A-II B-I + B-II
1) 1)
HD6-Trial
1) high risk patients, optional in phase II trial
GMMGstandardintensification
Rev. MTRev. MT + Elotuzumab
Rev. MT + Elotuzumab
2 x VRD + Elo. consolidation
2 x VRD consolidation 2 x VRD + Elo. consolidation
N 500 patients 3 years recruitment
MRD1
Questions to ask MRD2
Standard Risk
PI+Rd‐antiCD38 X4‐6
‐‐ Transplant or not‐ Consolidation or
Maintenance ‐‐ Consolidation or Maintenance‐ Duration of maintenanceObj. Cure?
+ HDT1 +PI+Pd‐anti CD38 X6
+HDT 2
‐ High risk? / MGUS like profile‐ More chemo?‐ Consolidation post ASCT #2?‐ Triplet maintenance‐ Duration: until PD
‐ ‐ Good risk?‐ Consolidation?‐ Maintenance, mono or combined?‐ Duration of maintenance
High RiskPI+RD‐anti CD38 X6
→ HDT 1 + PI+PD‐Dara X 6
→ HDT 2 → REV + Dara Maint
IFM to come
Obj. PFS/OS
Obj. PFS/OSDo your best…
70Optimising High-Risk MM OutcomesMUK9 Trial: OPTIMUM (CI M Kaiser/M Jenner)
MAb+PI+IMiD
Central MRDPFS + PFS2
Statistically FormalisedComparison
620 NDMM patientsCentral Risk Profiling
GEP + Genetics
PI+MEL-ASCT
High-Risk
Induction
Augmented ASCT
MAb+PI+IMiD
Intensified Consolidation & Maintenance
Standard-RiskData recording of ‘real-world’ outcomes
NCRI Myeloma XI
‚winning‘ arm
High-RiskMolecularly &
Clinically Matched
GEM2017FITFit elderly newly diagnosed MM patients non-transplant candidates
Primary end-point: Immunophenotypic CR after 18 induction cyclesSecondary end-point: PFS
New Startegies…CAR-T cells
76
CAR : Chimeric antigen receptor Adoptive transfer of T lymphocytes CAR expressing
CD19- CAR T cells in MM
Garfall AL, et al. NEJM 2015
BCMA- CAR T cells in MM
Both patients treated on the fourth dose level had toxicity consistent with cytokine-release syndrome
Both patients had prolonged cytopenias
Ali SA, et al. Blood 2015
ANTI-BCMA T CELLS IN RRMM (PHASE 1 TRIAL)OUTCOMES
• For most patients, LCAR-B38M cells were undetectable in peripheral blood > 4 months post-infusion
• Grade ≥ 3 AEs, n = 2 (5.7%)• No SAEs or deaths have occurred to date
79Zhang W, et al. EHA 2017: Abstract S103. Oral presentation.
OutcomesAnti-BCMA CAR T Cells
(N = 35)Response >1 year, n 5Progressive disease, n 2Relapse of extramedullary lesion, n 1
AE, adverse event; BCMA, B cell maturation antigen; CAR, chimeric antigen receptor; CRS, cytokine release syndrome; ORR, overall response rate; PR, partial response; SAE, serious AE; sCR, stringent complete response; VGPR, very good PR.
AUTHOR CONCLUSIONS• LCAR-B38M CAR-T cell technology exert rapid and reproducible therapeutic effects in RRMM• 12-month follow-up shows durable sCR• US clinical trial ongoing
CRS, n N = 35CRS free 6Grade 1 17Grade 2 10Grade 3 2Grade 4 0Grade 5 (death) 0
2
9
19
0%10%20%30%40%50%60%70%80%90%
100%
Best response
Patie
nts
sCRVGPRPR
• ORR: 100%
• The most common AE was CRS
Never give up!
Thank you for your attention