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2
Topics for Virtual Conference Series Smoldering myeloma Frontline therapy
Early relapse Key new role of immune therapies Future directions
3
Virtual ASH 2020 Myeloma Abstracts = 688 Oral = 179 Poster = 500 (Publications only 9) Total ASH abstracts for 2020 = 4,800 (down from 6,000) 4
Smoldering Myeloma 5
When Should Treatment Be Initiated? Potential New Myeloma or Smoldering Myeloma
Any Myeloma Defining Events? •CRAB •≥60% PC •FLC ≥100 •MRI >1 focal lesion
Treat as Myeloma Rajkumar SV © 2020
No Myeloma Defining Events (SMM)
High-Risk SMM (Median TTP ≈2 years)
Early Therapy With Len or Rd
Clinical Trials
Intermediate or Low-Risk SMM
Observation 6
Risk Score to Predict Progression Risk At 2 Years Score
100 High-risk group >12
0 2 3 5
0 3 4 0 2 3 5 6 2
80
% with progression
Risk Factor FLC Ratio 0-10 (ref) > 10-25 > 25-40 > 40 M protein (g/dL) 0-1.5 (ref) > 1.5-3 >3 BMPC% 0-15 (ref) > 15-20 > 20-30 > 30-40 > 40 FISH abnormality
Intermediate-risk group (9-12)
Low-intermediate-risk Group (5-8)
60
40 Low-risk group (0-4) 20
0 0
6
12
18
24
30
36
42
48
54
60
Months
Risk Stratification Groups
Hazard Ratio (95% CI) Versus Low-risk group (censored 2 year)
0-4
Reference
5-8
7.56 (3.77 to 15.2)
9-12
17.3 (8.63 to 34.8)
> 12
31.9 (15.4 to 66.3)
Total Risk Score
2-year Progression n (%)
0-4
9 / 241 (3.7%)
5-8
67 / 264 (25.4%)
9-12
65 / 133 (48.9%)
> 12
37 / 51 (72.6%)
# at Risk
0-4
241
238
229
213
194
175
153
117
100
76
63
5-8
264
256
229
197
174
145
118
91
73
53
44
9-12
133
119
98
73
59
47
33
26
20
14
13
>12
51
41
29
21
14
9
7
5
2
2
2
San Miguel. ASCO 2019. Abstr 8000. Mateos Blood Cancer J. 2020;10:102.
7
Phase III QuiRedex with Len/Dex vs Observation: OS From Progression To Active Disease Median follow-up: 10.8 years
Len-dex, median OS: 6.4 yrs
Observation, median OS: 4.7 yrs
Early treatment does not induce more resistant relapses 8 Mateos. EHA 2020. Abstr EP950.
Abstract #57
9
Interim analysis Risk of progression to active MM according to the 2/20/20 model 1 Low-risk 1/18 (5%)
18/150 (12%)
Intermediate-risk 7/18 (39%)
High-risk 15/132 (11%)
132/150 (88%) No progression
High-risk 10/18 (56%)
Low-risk 61/132 (46%)
Progression
Intermediate-risk 55/132 (42%)
10
8/18 SMM patients with progressive disease were not high-risk according to the 2/20/20 model1 1.
Mateos MV, et al. Blood Cancer J. 2020;10(10):102.
Risk-stratification according to CTC numbers in PB Patients with >1 CTC/µL showed significantly higher risk of transformation HR: 5.1 (95% CI 2.0 – 13.4); P < .001
Time-to progression (%)
100
75
Median TTP, 6 months 50
25
0
0 Number at risk ≤1 CTC/µL 135 >1 CTC/µL 15
120
240
360
480
600
Time from study entrance (days) 65 8
33 3
13 2
6 1
0 0
11
Immune kinetics in PB from baseline until disease progression Interim analysis in patients with longitudinal samples (N = 7) NK-cell compartment
T-cell compartment
P = .034
P = .042 8
1.0
15
0.8
2 2
0.6
% cells
4
4 % cells
% cells
6
% cells
P = .026
P = .011
6
0.4
10
5
0.2
0
Baseline
Progression
0
0.0
0
Baseline
Progression
Baseline
Progression
Baseline
Progression
CD4 effector memory
CD8
T gamma-delta
Adaptive
CXCR3+, CCR4+,CCR6-
CD127+, CD28+,TIGIT+, PD1+
CD62L-, CD39-, HLADR-, CD69n, CD27-
CD39-, HLADR-,CD16TCRgd+, CD69n, CD27-
12 Significant decrease in helper effector memory CXCR3+CCR4+ and cytotoxic CD127+TIGIT+PD1+ T cells, together with a significant increase in Tγδ CD69+ T cells and adaptive NK cells
Q&A 13
Frontline Therapy 14
Myeloma: Frontline Treatment Newly Diagnosed MM Not Transplant Candidate
1 - D-Rd
Transplant Candidate
1 - VRD or Dara-based quad induction 2 â&#x20AC;&#x201C; VTD / VCD
2 - VRD followed by Len (VMP-Dara; Rd)
Auto-SCT Maintenance [Len for std risk; (Len)+PI-based for high risk] Tandem for high-risk
No Delayed Transplant Outside clinical trials 15 P. Moreau
Phase III Trials in NDMM Not Eligible for ASCT Trial
Regimen
n
mPFS
mOS
Vista1
VMP
344
24 (TTP)
56.4
FIRST2
Rd cont
535
26
59.1
SWOG7773
VRD
242* 91**
43 34
75 65
Endurance4
VRD
542 # 167 ##
34.4 37
3-year: 84% NA
Alcyone5
VMP-Dara
356
36.4
42-Mo: 75%
MAIA6
Rd-Dara
368
30-Mo: 71%
Immature
*: median age: 64; ** > 65 years; # median age 65; ## > 70 years 1. San Miguel. ASH. 2011. Abstr. 476. 2. Facon. Blood. 2018;131:301. 3. Durie. Lancet. 2017;389:519. 4. Kumar. ASCO 2020 Abstr LBA3. 5. Mateos. ASH 2019. Abstr 859. 6. Facon. NEJM. 2019;380:2104.
16
ASH2020 – Kumar et al – MAIA Follow-up : 4 years
Median NR (55+ ?) vs 34 mos
Kumar. ASH 2020. Abstr 2276.
17
18
19
20
21
Abstract #143
22
Updated PFS (primary endpoint) Median follow up
89.8 months
Median PFS 47.3 months (Transplantation, arm B)
Median PFS 35 months (RVD alone, arm A) HR (95CI)
0.70 [0.59;0.83]
30% reduction in the risk of progression or death in patients receiving transplant
23
OS
Median follow up
89.8 months
8y-OS 62.2% (Transplantation, arm B) 8y-OS 60.2% (RVD alone, arm A)
HR (95CI)
1.03 [0.8;1.32]
More than 60% of the patients in the two arms are alive after 8 years of follow-up
24
Subgroup analyses Median follow up
89.8 months
MRD negativity rate 50 45 40
35
29.79 %
30 25
p 0.01
20.4 %
20 15
10 5 0
RVD alone
Transplant
Transplant is superior to VRD alone, even in patients who achieved undetectable MRD at 10-6 25
Q&A 26
Early Relapse 27
Myeloma: First Relapse First Relapse Not Refractory to Lenalidomide
1 - DRd
Alternatives including: KRd, IRd, ERd; Kd-Dara / Kd-Isa
Refractory to Lenalidomide
Kd-dara, Kd-Isa Pom-Vd, (PomD-Dara, PD-Isa)
Alternatives: KPD, PDElo Frail: Pd, IxaPd, PCD
! Challenge : patients progressing on frontline dara
28 P. Moreau
Q&A 29
Key new role of immune therapies 30
Triple-Class Refractory: When All Else Fails Monoclonal Antibodies
IMiDs / CELMoDs/ Novel Drugs
BCMA Abs
Chemotherapy
HDAC / ADC XPO inhibitors
Bispecifics/ ADCs
Cellular therapies BCMA CARs
Doxorubicin, Liposomal doxorubicin
Panobinostat/ Vorinostat
CC-220 Next Gen 38 (Iberdomide), SAR442085 CC-92480
Teclistamab AMG-701, CC-93269
Cilta-cel (JNJ-4528) Ide-cel (bb2121), Orva-cel (JCARH125)
Cyclophosphamide, Bendamustine, Melphalan
Belantamab Mafodotin
TAK-079, TAK-573, TAK-169
Venetoclax Melflufen
TNB-3838, REGN5458 PF-06863135
LCAR-B38M, bb21217, P-BCMA-101
Selinexor
MOR202, Others
BFCR4350A Talquetamab
MEDI2228, CC-99712 FOR46
Lummicar-2 (CT053) ALLO-715 ALLO-605 (TurboCAR)
PACE, HyperCAD
*Blue = approved
Green = ongoing clinical trials
31
Abstract #177
32
CARTITUDE-1: CONSORT Diagram Enrolled/apheresed, N=113 Lymphodepletion, n=101
Discontinued, n=12 Progressive disease, n=2 Withdrawal by subject, n=2 Death,a n=8
Discontinued, n=4 Withdrawal by subject, n=3 Death,a n=1
Treated with cilta-cel, n=97 Phase 1b, n=29
Phase 2, n=68 Discontinued study, n=9
Discontinued study, n=5
Death, n=9
Death, n=5
Ongoing, n=24
Ongoing, n=59
A total of 73 patients received bridging therapy Median turnaround timeb for cilta-cel was 29 days No patient discontinued due to manufacturing failure aDeaths
due to progressive disease (5), acute cardio-respiratory arrest (1), sepsis (1), subdural hematoma (1), and acute respiratory failure (1; after lymphodepletion). time was defined as time from receipt to release of product.
bTurnaround
33
62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177
CARTITUDE-1: ORR and MRD Assessment ORRa: 96.9% (94/97) N
Frequency in evaluable patients n=57c
Frequency in all treated n=97d
Overall MRD-
53
93.0%
54.6%
MRD- and sCR
33
57.9%
34.0%
MRD- and ≥VGPR
49
86.0%
50.5%
100%
Patients
80%
60%
sCR: 67.0%
67.0%
≥VGPR: 92.8%
Median time to first response: 1 month (0.9–8.5)
40%
Responses ongoing in 70 (72.2%) patients
20%
Of evaluable patients, 93.0% achieved MRD 10-5 negativity 25.8%
0% Best responseb =
̶
4.1%
sCR
VGPR
PR
Median time to MRD 10-5 negativity: 1 month (0.8–7.7)
Among patients with 6 months individual follow-up, most had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood
34
CAR, chimeric antigen receptor; CR, complete response; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. a PR or better, Independent Review Committee assessed. bNo patient had CR or stable disease as best response. cMRD was assessed in evaluable samples at 10 -5 threshold by next-generation sequencing (clonoSEQ, Adaptive Biotechnologies) in all treated patients at Day 28, and at 6, 12, 18, and 24 months regardless of the status of dise ase measured in blood or urine; patients were not evaluable primarily due to lack of an identifiable clone in the baseline bone marrow sample. dAll treated patients. 62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177
CARTITUDE-1: Deaths N=97
Time of death post cilta-cel infusion, days
14
45â&#x20AC;&#x201C;694
5
253â&#x20AC;&#x201C;694
Pneumonia
1
109
Acute myelogenous leukemia a
2
418; 582
Sepsis and/or septic shock
2
45; 162
CRS/HLH
1
99
Lung abscess
1
119
Respiratory failure
1
121
Neurotoxicity
1
247
Total deaths during the study, n
Due to progressive disease AEs unrelated to treatment (n=3)
AEs related to treatment (n=6)
35
AE, adverse event; CRS, cytokine release syndrome; HLH, hemophagocytic lymphohistiocytosis; MDS, myelodysplastic syndrome. aOne patient with acute myelogenous leukemia had MDS and a cytogenetic profile consistent with MDS (del20q [present prior to cilta-cel infusion], loss of 5q); the other had prostate cancer and squamous cell carcinoma of the scalp. 62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177
CARTITUDE-1: Conclusions Cilta-cel has a manageable safety profile at the recommended phase 2 dose ̶
CRS was mostly grades 1/2; median time to onset of CRS was 7 days (range, 1–12) ̶
CAR-T-related neurotoxicities occurred in 20 patients (20.6%); 10.3% had grade ≥3
Low dose of cilta-cel yielded early, deep, and durable responses in heavily pretreated relapsed/refractory MM ̶ 96.9% ORR, with sCR 67.0% ̶ Median PFS not reached; 12-month PFS rate was 76.6%, OS rate was 88.5%
Cilta-cel is under further investigation in other populations of patients with MM in earlier-line settings ̶
Outpatient administration is being studied in CARTITUDE-2 (NCT04133636) and CARTITUDE-4 (NCT04181827)
AE, adverse event; CAR-T, chimeric antigen receptor T cell; CRS, cytokine release syndrome; MM, multiple myeloma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; sCR, stringent complete response.
36
62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177
Abstract #131
37
CRB-401
Best response 100
Patients, %
80 60 40 20 0
ORR = 100% sCR
ORR = 89.5%
CR
33.3
VGPR
31.6
PR
ORR = 50.0% ORR = 33.3% 33.3
50 50 × 106 (n = 3)
33.3
≥ CR = 38.9%
ORR = 75.8%
≥ CR = 36.8%
30.6
5.3
42.1
≥ CR = 100%
≥ CR = 38.7%
8.1
66.7 25.8
5.6
11.1
10.5
150150 × 106 (n = 18)
450450 × 106 (n = 38)
11.3
800800 × 106 (n = 3)
Total Total (N = 62)
All 15 patients with ≥ CR who had a qualified assessment were MRD negative by NGSa
aOf
24 patients with ≥ CR, 8 had no MRD assessment and 1 had an assessment outside of the 3-month window; Lin Y, et al. ASH 2020. Abstract 131.
10-4 sensitivity.
38
CRB-401
Conclusions • Updated results from CRB-401 demonstrated deep and durable responses with ide-cel in heavily pretreated patients with RRMM – Efficacy and safety reflect prior reports and support a favorable clinical benefit-risk profile for ide-cel at target dose levels ≥ 150 × 106 CAR+ T cells, with a median OS of 34.2 months in a highly triple-class– exposed population and half of ongoing responders achieving DOR > 2 years
• In the pivotal phase 2 KarMMa trial, ide-cel treatment resulted in favorable risk/benefit profile in triple-class exposed RRMM 1 – ORR 73% (including CR rate 33%)
– Median DOR 10.7 months, median PFS 8.8 months, median OS 19.4 months
• Ide-cel is also being explored in ongoing clinical trials:
KarMMa-2
Phase 2 study of ide-cel in triple-class–exposed patients and patients with high-risk MM (PD within 18 months of 1L or inadequate response to ASCT); NCT03601078
KarMMa-3
Phase 3 study of ide-cel vs standard regimens in triple-class–exposed patients with 2-4 prior lines of therapy; NCT036511282
KarMMa-4
Phase 1 study of ide-cel in patients with high-risk NDMM (R-ISS stage III disease per IMWG criteria); NCT041964913
1. Munshi NC, et al. J Clin Oncol 2020;38(suppl) [abstract 8503]; 2. Delforge M, et al. ASH 2020 [abstract 2323]; 3. Usmani SZ, et al. ASH 2020 [abstract 1418]. Lin Y, et al. ASH 2020. Abstract 131.
39
Biallelic Loss of BCMA Triggers Resistance to Anti-BCMA CAR T Cell Therapy in Multiple Myeloma Mehmet K. Samur, Mariateresa Fulciniti, Anil Aktas-Samur, Abdul Hamid Bazarbachi, YuTzu Tai, Timothy B. Campbell, Fabio Petrocca, Kristen Hege, Shari Kaiser, HervĂŠ Avet Loiseau, Kenneth Anderson and Nikhil C. Munshi 40 40
BCMA, located on 16p, was deleted
Copy Number Alterations detected by scRNAseq
Copy Number Alterations detected by WES
41
BCMA had a biallelic loss, one allele was deleted, and the second allele was mutated
% of single cells in PC cluster with CNA
~60%-70% of cells detected with BCMA stop codon mutation TP53 missense mutation was clonal
42
del16p significantly co-occurs with del17p
• del16p was observed in 4-14% of newly diagnosed patients on different datasets. • Half of the del16p events were subclonal • Mono-allelic del16p co-occurs with del17p in 77% of the del16p patients. (6X enrichment, hypergeometric test p-value=3.38e-11) • 30-40% of patients with del17p also carried del16p.
Deletion does not effect the BCMA expression at diagnosis
• Our previous study about the chronology of CNA events showed that relative timing for del16p and del17p events were similar
43
CAR-T Discussion
44
Bi-specific Antibodies
45
Abstract #180
46
Teclistamab: Overall Response Rate ORRa for SC Cohorts
80%
At the RP2D of 1500 µg/kg SC: 73%
60%
60%
46%
̶ ̶
Median time to first confirmed response was 1 month (0.3–3) 14/20 (70%) triple-class refractory patients responded 6/8 (75%) penta-drug refractory patients responded 15/16 (94%) responders are alive and progression-free after mF/U of 3.9 months (1.7–7.4)
n=4 n=1
n=4
40% n=3
̶
̶ ≥VGPR 55%
n=7
Most active doses were 270–720 µg/kg IV and 720–3000b µg/kg SC ̶ ̶
20%
̶
n=5 n=3
n=4
̶
ORRa at these doses was 69% (47/68) ≥VGPR was 59%; ≥CR was 26% 67% (18/27) ORR in IV cohorts and 71% (29/41) ORR in SC cohorts 44/47 (94%) responders remain on treatment with ongoing responses after mF/U of 6.5 months (1.7–14)
0% 80 + 240 µg/kg (n=13)
PR
720 µg/kg (n=15)
VGPR
CR
1500 µg/kg (RP2D) (n=22)
Of 11 evaluable patients across all IV and SC doses so far, 8 had MRDneg CR at 10-6 and 1 at 10-5 sensitivityc
sCR
CR, complete response; mF/U, median follow-up; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aAmong response-evaluable patients who had ≥1 study treatment and ≥1 postbaseline disease evaluation; includes unconfirmed responses.b4/4 patients responded at 3000 µg/kg SC dose. cPatient with MRD-neg CR at 10 -5 was indeterminate at 10 -6 due to insufficient cell counts.
47 Garfall A, et al. 62nd ASH Annual Meeting 2020. Abstract #180 Phase 1 Study of Teclistamab in RRMM
47
Teclistamab: Conclusions
Teclistamab was well-tolerated at the RP2D of 1500 µg/kg SC
̶ Maximum tolerated dose has not been identified ̶ All CRS events were grade 1–2 and generally confined to step-up and first full doses ̶ One grade 1 reversible neurotoxicity at RP2D ̶ No new safety signals were identified High response rate observed at the RP2D ̶ ORR at the RP2D (1500 µg/kg SC) was 73%; ≥VGPR was 55% and ≥CR was 23% • 14/20 (70%) triple-class refractory patients responded; 6/8 (75%) penta-drug refractory patients responded ̶ Responses appeared durable and deepened over time ̶ At median 3.9-month follow-up, 15/16 (94%) responders are alive and progression-free
Selection of the 1500 µg/kg SC RP2D was supported by promising safety, efficacy, PK, and pharmacodynamics
Teclistamab, an off-the-shelf therapy targeting BCMA, showed promising efficacy in heavily-pretreated patients with RRMM ̶ Phase 1 of the study is ongoing, and phase 2 expansion study has started
48 Garfall A, et al. 62nd ASH Annual Meeting 2020. Abstract #180 Phase 1 Study of Teclistamab in RRMM
Abstract #290
49
GPRC5D: G Protein-Coupled Receptor Class C Group 5 Member D
Orphan G protein-coupled receptor of unknown function Loop-3
Limited expression in healthy human tissue, primarily in plasma cells and hair follicles1-2
Loop-1
Highly expressed in myeloma cells and associated with poor prognostic factors in multiple myeloma (MM)1-3
Loop-4
Loop-2
No known shed peptides or extracellular domain shedding (reduced risk for sink effect) Ideal target for CD3 redirection
50 1Smith Sci
11(485):eaau7746. 2Pillarisetti
Blood 135(15):1232. 3Atamaniuk Eur J
Transl Med gammopathy of undetermined significance; SMM, smoldering multiple myeloma
Clin Invest 42(9):953. CD3, cluster of differentiation 3; MGUS, monoclonal
62nd
Chari et al. ASH Meeting 2020. Abstract #290 Phase 1 Study of Talquetamab in RRMM
Talquetamab: Overall Response Rate ORRa for SC Doses 80%
73%
At the RP2D of 405 µg/kg SC ̶
69% ORR (9/13) ̶
Median 3.7-month (1.7–6.5) follow-up for responders
̶
Median time to first confirmed response was 1 month (1–2) ̶
67% (6/9) of triple-class refractory patients responded ̶
100% (2/2) of penta-drug refractory patients responded
69% n=2
60%
50% n=1
14%
n=5
n=3
40%
20%
≥VGPR 39%
At most active doses of 20–180 µg/kg IV and 135–800 µg/kg SC
n=3 n=4
n=3
66% ORR (33/50) ̶
≥VGPR was 42% ̶
67% ORR (12/18) in IV cohorts and 66% ORRa (21/32) in SC cohorts
n=2
̶
0% 5–45 µg/kg SC n=14
135 µg/kg SC n=8
PR a
405 µg/kg SC (RP2D) n=13
VGPR
CR
800 µg/kg SC n=11
sCR
Among response-evaluable patients who had at least 1 study treatment and 1 postbaseline disease evaluation; includes unconfirmed responses. CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response, VGPR, very good partial respons e
51 62nd
Chari et al. ASH Meeting 2020. Abstract #290 Phase 1 Study of Talquetamab in RRMM
Talquetamab: Conclusions Talquetamab has a tolerable safety profile at the RP2D of 405 µg/kg SC Safety profile at the RP2D was generally consistent with safety at lower doses, with low incidence of infections ̶
Early DLT of Gr 3 maculopapular rash and dose reductions due to certain toxicities (skin rash, oral toxicity, back pain) were observed in 4/11 patients (36%) at 800 µg/kg SC weekly
̶
CRS was generally low grade with no grade ≥3 CRS with SC dosing Low incidence of neurotoxicity with no grade ≥3 events with SC dosing ̶
̶
High response rate observed at the RP2D ORR was 69% (9/13) at the RP2D of 405 µg/kg SC; 39% ≥VGPR • Median time to first confirmed response was 1 month • 6/9 triple-class refractory patients responded; 2/2 penta-drug refractory patients responded Responses were durable and continued to deepen over time ̶
̶
PK results indicate target exposure levels at the RP2D, and pharmacodynamic data demonstrate consistent T cell activation, cytokine production, and redistribution at the RP2D SC dosing is more convenient and may offer an opportunity for less frequent dosing Talquetamab, a first-in-class, off-the-shelf therapy targeting GPRC5D, showed encouraging efficacy in heavily-pretreated patients with RRMM ̶
Dose expansion is ongoing and phase 2 is planned
52 62nd
Chari et al. ASH Meeting 2020. Abstract #290 Phase 1 Study of Talquetamab in RRMM
Disadvantages
Advantages
BCMA Therapeutics – Advantages/Disadvantages Antibody–drug conjugate
CAR T-cells
Bispecific antibody
Off-the-shelf
Personalized
Off the shelf
Targeted cytotoxicity Not dependent on T-cell health
Targeted immuno-cytotoxicity
Targeted immuno-cytotoxicity
No lymphodepletion No steroids
Single infusion (“one and done”)
No lymphodepletion Minimal steroids
Available to any infusion center Outpatient administration
Potentially persistent Fact accredited center required (hospitalization likely required)
Initial hospitalization required
Currently requires REMS/Ophtho
CRS and Neurotoxicity; requires ICU and Neurology services
CRS and Neurotoxicity possible
Single agent activity low in CD38 refractory patients
Dependent on T-cell health (manufacturing failures)
Dependent on T-cell health (T-cell exhaustion)
Requires continuous administration
Requires significant support social – caregiver required
Requires continuous administration
$$
$$$$
$$$
53
Q&A 54
Future Directions
55
Myeloma: Second or Higher Relapse First Relapse Options
• Any first relapse options that have not been tried (2 new drugs; triplet preferred)
Isa-Pd, or DPd, or DKd, or KPd
Additional Options
• Belamaf • VDT-PACE like anthracycline containing regimens • Cyclo / benda / melphalan • Panobinostat + PI • Venetoclax [only t(11;14)] • Selinexor • Melflufen • CAR-T • Bispecific 56 P. Moreau
Newer IMiDs/Cel Mods
• Iberdomide (CC-220) (Cereblon ligase modulator)
− ASH 2020 Abstract 724: First Results of Iberdomide + Dara/Dex or Iberdomide + Vd in RR MM
• CC-92480
Image: Matyskiela. J Med Chem 2018;61:535
57
Myeloma: Future State Multiple Relapse
Refractory to IMiD, PI, Anti-CD38
Refractory to IMiD, PI, Anti CD38,
Alkylators, and Anti BCMA
Anti BCMA strategy
Existing drugs: Combinations with Cyclophosphamide
BCMA ADC
Elotuzumab
(eg., Belantamab)
Selinexor
New Monoclonals
Venetoclax
Iberdomide, CC-94480
Bispecific
Panobinostat
New ADCs
Anti BCMA
Bendamustine
New bi-specifics
VDT PACE
New CAR-Ts
that do not have IMiD, PI, Anti CD38
BCMA CAR-Ts Rajkumar SV © 2020
New Drugs:
58
Q&A 59
Replay available: https://www.myeloma.org/videos/ imwg-conference-series-ash-2020
60
Thank you to our sponsors!
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