MonumenTAL-3: Talquetamab + Daratumumab Moves Earlier in Relapsed Myeloma
A first-in-class GPRC5D bispecific antibody combined with daratumumab (± pomalidomide) beat standard DPd in relapsed/refractory multiple myeloma — presented at EHA 2026 (Abstract S100) with simultaneous publication in NEJM. The talquetamab combinations are investigational.
⚠ InvestigationalPhase 3 · RRMMGPRC5D × CD3 Bispecificn = 864EHA 2026 · S100Simul-pub NEJMSponsor: Johnson & Johnson
[Slide 1]
Figure S2. Patient Disposition
1104 Patients were
screened for eligibility
240 Patients failed screening
237 did not meet eligibility criteria
3 withdrew consent
864 Patients were
randomized (intent-to-treat
analysis set)
287 Assigned to
Tal-DP
287 Assigned
290 Assigned
to Tal-D
to DPd
11 Patients
13 Patients
7 Patients did
did not
did not
not receive
receive study
receive study
study
treatment
treatment
treatment
276 Received
274 Received
283 Received
37 Discontinued study
Tal-DP
41 Discontinued study
Tal-D
DPd treatment
67 Discontinued study
participation
treatment
participation
treatment
(safety
participation
30 due to death
(safety
34 due to death
(safety
analysis set)
59 due to death
1 lost to follow-up
analysis set)
1 lost to follow-up
analysis set)
8 patient withdrawal
6 patient withdrawal
6 patient withdrawal
82 Discontinued study
83 Discontinued study
149 Discontinued study
treatment
treatment
treatment
35 due to adverse event
23 due to adverse event
20 due to adverse event
1 lost to follow-up
5 due to physician decision
11 due to physician decision
4 due to physician decision
43 due to progressive disease
114 due to progressive disease
37 due to progressive disease
11 patients refused further
3 patients refused further
5 patients refused further
treatment
treatment
treatment
194 Patients still
1 other
191 Patients still
134 Patients still
1 other
on treatment
on treatment
on treatment
Eligible patients were randomized to receive talquetamab in combination with daratumumab and pomalidomide (Tal-DP), talquetamab in combination with
daratumumab (Tal-D), or daratumumab in combination with pomalidomide and dexamethasone (DPd).
---
[Slide 2]
Table S6. Relative Dose Intensity (Safety Population)*
Tal-DP
Tal-D
DPd
(N=276)
(N=274)
(N=283)
Talquetamab relative dose intensity, .:
No.
275
273
-
Median, % (range)
95.4 (5-109)
97.1 (6-108)
-
Daratumumab relative dose intensity
No.
276
274
283
Median, % (range)
96.9 (33-109)
100 (33-150)
94.6 (6-100)
Pomalidomide relative dose intensity
No.
270
-
283
Median, % (range)
82.0 (5-104)
-
75.6 (9-100)
Tal-DP, talquetamab plus daratumumab and pomalidomide Tal-D, talquetamab plus daratumumab; DPd, daratumumab plus
pomalidomide and dexamethasone.
* Safety population includes all patients who received at least one dose of study treatment.
+ Includes step-up doses and any repeated step-up doses, if applicable. For talquetamab, patients who switched to the
monthly schedule received a planned dose of 0.8 mg/kg every 4 weeks. Switching at Cycle 5 was optional for patients who
achieved very good partial response or better at investigator discretion. From Cycle 7, switching to 0.8 mg/kg every 4 weeks
was required for patients who achieved partial response or better.
# Relative dose intensity is calculated considering planned dose per protocol.
---
[Slide 3]
Table S7. Treatment Cycle Delays, Incidence, and Reasons for Study Treatment Dose
Modification (Safety Population)*
Tal-DP
Tal-D
DPd
(N=276)
(N=274)
(N=283)
Patients with >1 cycle delays, n (%)
226 (81.9)
201 (73.4)
155 (54.8)
Patients who received talquetamab, n (%) t.t
275 (99.6)
273 (99.6)
-
Patients with talquetamab skipped, n (%)§
174 (63.3)
120 (44.0)
-
Patients with talquetamab delay, n (%)$
58 (21.1)
59 (21.6)
-
Patients who received daratumumab, n (%)+
276 (100)
274 (100)
283 (100)
Patients with daratumumab skipped, n (%)$
196 (71.0)
143 (52.2)
214 (75.6)
Patients with daratumumab delay, n (%)$
63 (22.8)
55 (20.1)
15 (5.3)
Patients who received pomalidomide, n (%)+
270 (97.8)
-
283 (100)
Patients with pomalidomide skipped, n (%)$
222 (82.2)
-
231 (81.6)
Patients with pomalidomide reduced, n (%)$
114 (42.2)
-
171 (60.4)
Tal-DP, talquetamab plus daratumumab and pomalidomide Tal-D, talquetamab plus daratumumab; DPd, daratumumab plus
pomalidomide and dexamethasone.
* Safety population includes all patients who received at least one dose of study treatment.
+ Percentages are calculated with the number of patients in the safety population in each treatment arm as the denominator.
$ Includes patients who received at least one dose of talquetamab.
$ Percentages are calculated with the number of patients who received the corresponding drug as the denominator.
[Slide 1]
A Progression-free Survival, Tal-DP vs. DPd
24-mo Progression-free
survival
100
90
Tal-DP
80
81.3 (95% CI,
Percentage of Patients Alive
without Disease Progression
70
75.8-85.7)
60
50
DPd
40
51.2 (95% CI,
44.8-57.1)
30
20
Hazard ratio for disease progression
10
or death, 0.28 (95% CI, 0.20-0.40)
P<0.001
0
0
3
6
9
12
15
18
21
24
27
30
33
36
Months
No. at Risk
Tal-DP
287
266
255
240
229
218
212
169
116
74
32
8
0
DPd
290
249
223
198
175
158
146
113
81
44
22
2
0
B Progression-free Survival, Tal-D vs. DPd
24-mo Progression-free
survival
100
90
77.6 (95% CI,
71.7-82.5)
80
Tal-D
Percentage of Patients Alive
without Disease Progression
70
60
50
DPd
40
51.2 (95% CI,
44.8-57.1)
30
20
Hazard ratio for disease progression
10
or death, 0.33 (95% CI, 0.24-0.46)
P<0.001
0
0
3
6
9
12
15
18
21
24
27
30
33
36
Months
No. at Risk
Tal-D
287
262
256
238
225
216
207
159
98
62
30
8
0
DPd
290
249
223
198
175
158
146
113
81
44
22
2
0
Figure 1. Progression-free Survival (Intention-to-Treat Population).
Shown are Kaplan-Meier estimates of progression-free survival in the
Tal-DP group as compared with the DPd group (Panel A) and in the Tal-D
group as compared with the DPd group (Panel B). Tick marks indicate cen-
sored data. At a median follow-up of 24.6 months, the P values for Tal-DP
and Tal-D crossed the O'Brien-Fleming stopping boundaries for superiority
(P=0.0069 for Tal-DP; P=0.0145 for Tal-D). Median progression-free sur-
vival could not be estimated in the Tal-DP and Tal-D groups and was 24.4
months (95% CI, 19.3 to not estimated) in the DPd group. At the clinical
cutoff, disease progression or death had occurred in 241 of 864 patients:
48 in the Tal-DP group, 57 in the Tal-D group, and 136 in the DPd group.
The intention-to-treat population included all the patients who had under-
gone randomization. DPd denotes daratumumab plus pomalidomide and
dexamethasone, Tal-D talquetamab plus daratumumab, and Tal-DP talque-
tamab plus daratumumab and pomalidomide.
---
[Slide 2]
A Overall Survival, Tal-DP vs. DPd
24-mo Overall
survival
100
89.2 (95% CI,
84.9-92.4)
Tal-DP
90
80
70
79.1 (95% CI,
DPd
Percentage of Patients Alive
73.7-83.6)
60
50
40
30
20
10
Hazard ratio for death, 0.47
(95% CI, 0.30-0.73)
0
0
3
6
9
12
15
18
21
24
27
30
33
36
Months
No. at Risk
Tal-DP
287
277
276
269
262
248
238
200
141
94
48
10
0
DPd
290
278
264
255
245
226
217
173
125
78
37
4
0
B Overall Survival, Tal-D vs. DPd
24-mo Overall
survival
100
87.9 (95% CI,
83.0-91.5)
90
Tal-D
80
70
79.1 (95% CI,
DPd
Percentage of Patients Alive
73.7-83.6)
60
50
40
30
20
10
Hazard ratio for death, 0.51
(95% CI, 0.33-0.78)
0
0
3
6
9
12
15
18
21
24
27
30
33
36
Months
No. at Risk
Tal-D
287
276
275
268
264
256
251
199
130
77
40
10
0
DPd
290
278
264
255
245
226
217
173
125
78
37
4
0
Figure 2. Overall Survival (Intention-to-Treat Population).
Shown are Kaplan-Meier estimates of overall survival in the Tal-DP group
as compared with the DPd group (Panel A) and in the Tal-D group as com-
pared with the DPd group (Panel B). Tick marks indicate censored data. At
a median follow-up of 24.6 months, the P values (P=0.0006 for Tal-DP;
P=0.0015 for Tal-D) did not cross the prespecified stopping boundaries for
superiority, given the nominal alpha level allocated for each comparison at
the interim analysis (0.0001). At the clinical cutoff, death had occurred in
123 of 864 patients: 30 in the Tal-DP group, 34 in the Tal-D group, and 59
in the DPd group. The intention-to-treat population included all the pa-
tients who had undergone randomization.
[Slide 1]
Table S20. GPRC5D-associated Adverse Events (Safety Population)*
Tal-DP
Tal-D
DPd
Parameter
(N=276)
(N=274)
(N=283)
Taste changes +
201 (72.8)
205 (74.8)
11(3.9)
Leading to talquetamab dose delays or skips, n (%)
18 (6.5)
15 (5.5)
Leading to discontinuation of talquetamab, n (%);
11 (4.0)
6(2.2)
-
Leading to discontinuation of all study treatment, n (%)
5(1.8)
0
0
Duration, median (range). days
183 (3-909)
217 (2-934)
169(1-353)
Patients who received supportive measures, n (%)
8(13.8)
(10.9)
0
Outcome, (%)'
Number of events
226
229
11
Recovered or resolved
(58.0)
129 (56.3)
4(36.4)
Not recovered or resolved
86 (38.1)
(40.2)
7(63.6)
Recovered or resolved with sequelae
1 (0.4)
1 (0.4)
0
Recovering or resolving
1 (0.4)
2(0.9)
0
Missing
7(3.1)
5(2.2)
0
Non-rash skin adverse events #
191 (69.2)
177 (64.6)
24(8.5)
Grade 3.n (%) **
6(2.2)
7(2.6)
0
Leading to talquetamab dose delays or skips, n (%)
12 (4.3)
10 (3.6)
-
Leading to discontinuation of talquetamab, n (%):
5(1.8)
2(0.7)
-
Leading to discontinuation of all study treatment, n (%)$
2(0.7)
1 (0.4)
0
Duration, median (range). days
43
46
13
(1-714)
(1-732)
(2-512)
Patients who received supportive measures, n (%)
113(40.9)
107 (39.1)
13(4.6)
Outcome. (%)
Number of events
348
291
26
Recovered or resolved
279(80.2)
(73.9)
21 (80.8)
Not recovered or resolved
63(18.1)
71(24.4)
5(19.2)
Recovered or resolve with sequelae
1 (0.3)
1 (0.3)
0
Recovering or resolving
1 (0.3)
1 (0.3)
0
Missing
4(1.1)
3(1.0)
0
Nail-related adverse events
155(56.2)
57(57.3)
1 (0.4)
Grade (%) **
1 (0.4)
1 (0.4)
0
Leading to talquetamab dose delays or skips, n (%)
4(1.4)
4(1.5)
Leading to discontinuation of talquetamab, n (%):
3(1.1)
0
0
Leading to discontinuation of all study treatment. n (%)3
0
0
0
Duration, median (range). days
176(1-815)
171 (1-924)
(64-64)
Patients who received supportive measures, n (%)
(12.7)
30(10.9)
0
Outcome, (%)
Number of events
199
206
1
Recovered or resolved
109 (54.8)
90(43.7)
1 (100)
Not recovered or resolved
83(41.7)
(49.0)
0
Recovered or resolve with sequelae
0
0
0
Recovering or resolving
3(1.5)
2(1.0)
0
Missing
4(2.0)
13 (6.3)
0
Rash-related adverse events **
105 (38.0)
107 (39.1)
43(15.2)
Grade (%) **
5(1.8)
7(2.6)
1 (0.4)
Leading to talquetamab dose delays or skips, n (%)
7(2.5)
5(1.8)
Leading to discontinuation of talquetamab, n (%):
1 (0.4)
2(0.7)
Leading to discontinuation of all study treatment, n (%) $
0
1 (0.4)
0
Duration, median (range). days
21 (1-920)
(1-662)
9(1-121)
Patients who received supportive measures, n (%)
75 (27.2)
84(30.7)
32(11.3)
Outcome, n (%)
43
Tal-DP
Tal-D
DPd
Parameter
(N=276)
(N=274)
(N=283)
Number of events
173
152
56
Recovered or resolved
161 (93.1)
129 (84.9)
51 (91.1)
Not recovered or resolved
11(6.4)
(13.8)
4(7.1)
Recovered or resolve with sequelae
0
1 (0.7)
0
Recovering or resolving
0
1 (0.7)
0
Missing
1 (0.6)
0
1 (1.8)
Tal-DP. talquetamab plus daratumumab and pomalidomide; Tal-D, talquetamab plus daratumumab; DPd, daratumumab
plus pomalidomide and dexamethasone
*The fety population was defined as all randomized patients who received at least one dose of study treatment
f Including ageusia, dysgeusia (maximum grade 2 severity per Common Terminology Criteria for Adverse Events v5.0),
hypogeusia, and taste disorder.
: Events with action taken to talquetamab as drug withdraws on the adverse event electronic clinical report form page.
$ Includes those patients indicated as having discontinued all study treatment due to adverse events on the I-of-treatment
clinical report form page.
Total number of events for the given treatment arm is used as the denominator.
# Including skin exfoliation, dry skin, pruntus, and palmar-plantar erythrodysesthesia syndrome.
I Including nail discoloration, nail disorder, onycholysis, onychomadesis, onychoclasis, nail dystrophy, nail toxicity, and
nail ridging.
Including rash, maculopapular rash, crythematous rash, and erythema.
ff There were no grade N events.
---
[Slide 2]
Figure S5. Mean Body Mass Index (kg/m²) Over Time by Body Mass Index at Baseline (Safety Population)
(A) Tal-DP
40
Obese
Mean (SE) Body Mass Index (kg/m²)
D.
X
30
@
D
Overweight
Healthy weight
20
0
Underweight
C201
C3D1
CAD1
CSD1
C6D1
CTD1
CBD1
C9D1
C1001
C1C101201
C1301
C1401
C1501
C1601
C1701
C1801
C1901
C2002101
10223
C23D1
C24D1
C25D1
C2801
C3001
C34D1
Visit
No. of Patients
Underweight 3 3 3 3 3 3 3 3 3 3 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0
Healthy weight
94
90
89
85
80
80
78
74
73
68
64
61
61
58
55
54
51
49
48
46
44
43
38
36
31
27
26
20
14
12
9
7
6
5
4
3
1
0
0
Overweight
117
110
105
104
102
97
96
95
89
89
88
84
84
83
80
77
76
74
72
72
69
63
55
43
32
30
27
26
21
21
17
10
9
6
5
2
1
1
1
Obese 62 59 57 56 53 53 54 53 51 52 50 51 48 48 47 47 46 46 47 42 39 38 35 28 26 26 22 17 12 10 8 5 3 2 1 1 1 1 0
Underweight
Healthy weight
Overweight
-
-
Obese
[Slide 1]
Summary/Conclusion:
Tal-DP and Tal-D demonstrated a significant and profound PFS benefit VS DPd, clinically meaningful OS improvements and gr >3 infection rates similar to or lower than
DPd. Tal was combinable, with low rates of tx d/c. Efficacy appeared numerically better with Tal-DP VS Tal-D but with a higher gr 3-4 cytopenia rate, as expected with
Pom. Tal-D with or without Pom represents a new standard of care for RRMM as early as 2L across all practice settings.
A
B
+ Tal-DP + DPd
Tal-DP
100
Tal 0.8 mg/kg SC Q2W from
C1 through C4-6 then Q4W"
24-mo PFS (95% CI)
81.3% (75.8-85.7)
Dara 1800 mg SC QW for
C1-2, Q2W C3-6, then Q4W
80
Pom 2 mg daily for 21 days
per C from C2b
% of patients progression-free and alive
60
24-mo PFS (95% CI)
51.2% (44.8-57.1)
Tal-D
Tal 0.8 mg/kg SC Q2W from
40
C1 through C4-6 then Q4W
Dara 1800 mg SC QW for
C1-2, Q2W C3-6, then Q4W
20
Tal-DP
DPd
N=287
N=290
Median PFS (95% CI), mo
NR (NE-NE)
24.4
(19.3-NE)
DPd
HR (95% CI)
0.28 (0.20-0.40)
P<0.0001
Dara 1800 mg SC QW for
0
C1-2, Q2W C3-6, then Q4W
0
3
6
9
12
15
18
21
24
27
30
33
36
Pom 4 mg daily for 21 days
Months
per C from C1
Number at Risk
Dex 40 mg (age <75) or 20 mg
Tal-DP
287
266
255
240
229
218
212
169
116
74
32
8
0
(BMI <18.5 or age >75) QW
DPd
290
249
223
198
175
158
146
113
81
44
22
2
0
C
Tal-D
DPd
100
24-mo PFS (95% CI)
80
77.6% (71.7-82.5)
Clinical cut-off: November 2025.
Median follow-up was 24.6 mo
(range 0.03-35.4). For panels B and
C, PFS was estimated using the
% of patients progression-free and alive
60
24-mo PFS (95% CI)
Kaplan-Meier method; treatment
51.2% (44.8-57.1)
comparisons were made using a
stratified log-rank test. HRs and
95% Cls were calculated using a Cox
40
proportional hazards model. Disease
evaluations were by independent
review committee per IMWG
criteria. BMI, body mass index; C,
cycle; Dex, dexamethasone; SC,
20
Tal-D
DPd
subcutaneous; QW, weekly; Q2W,
N=287
N=290
every other week; Q4W every 4
Median PFS (95% CI), mo
NR (NE-NE)
24.4 (19.3-NE)
weeks.
HR (95% CI)
0.33 (0.24-0.46)
P<0.0001
"Tal could be reduced to Q4W at
0
C5-6 with a very good partial
response or better or at C7 with a
0
3
6
9
12
15
18
21
24
27
30
33
36
partial response or better. Pom
Months
Number at Risk
could be increased to 4 mg at C3D1
if indicated.
Tal-D
287
262
256
238
225
216
207
159
98
62
30
8
0
DPd
290
249
223
198
175
158
146
113
81
44
22
2
0
[Slide 1]
Table S19. Treatment-emergent Ataxia/balance disorders (Safety Population)*
Tal-DP
Tal-D
DPd
Parameter
(N=276)
(N=274)
(N=283)
Ataxia and balance disorders +
40 (14.5)
34 (12.4)
1 (0.4)
Ataxia
15 (5.4)
14 (5.1)
0
Dysarthria
12 (4.3)
11 (4.0)
0
Balance disorder
8 (2.9)
7 (2.6)
0
Nystagmus
8 (2.9)
1 (0.4)
0
Cerebellar ataxia
4 (1.4)
1 (0.4)
0
Cerebellar syndrome
3 (1.1)
1 (0.4)
0
Dysmetria
1 (0.4)
0
0
Gait disturbance
8 (2.9)
10 (3.6)
1 (0.4)
Grade 3, n (%) :
8 (2.9)
6 (2.2)
0
Leading to talquetamab dose delays or skips, n (%)
21 (7.6)
23 (8.4)
-
Leading to discontinuation of talquetamab, n (%)§
13 (4.7)
6 (2.2)
-
Leading to discontinuation of all study treatment, n (%)
7 (2.5)
0
0
Time to onset from first dose of study treatment, median
292 (3-1034)
326 (24-873)
21 (21-21)
(range), days
Duration, median (range), days
106.5
108.0
-
(10-808)
(1-385)
Outcome, n (%) #
Number of events
93
65
1
Recovered or resolved
10 (10.8)
11 (16.9)
0
Not recovered or resolved
82 (88.2)
44 (67.7)
0
Recovered or resolved with sequelae I
0
1 (1.5)
0
Recovering or resolving
1 (1.1)
5 (7.7)
0
Missing
0
4 (6.2)
1 (100)
*The safety population was defined as all randomized patients who received at least one dose of study treatment.
+ Including ataxia, dysarthria, balance disorder, nystagmus, cerebellar ataxia, cerebellar syndrome, dysmetria, and gait
disturbance.
: There were no grade >4 events.
$ Events with action taken to talquetamab as drug withdrawn on the adverse event electronic clinical report form page.
1 Includes those patients indicated as having discontinued all study treatment due to adverse events on the end-of-treatment
clinical report form page.
# Total number of events for the given treatment arm is used as the denominator.
I Indicates that the adverse event was recorded as resolved at the time of reporting, but the patient subsequently had
persistent, recurrent, or later-emerging neurologic findings within the overall clinical course. This does not imply
continuous unresolved symptoms from the index event.
[Slide 1]
The NEW ENGLAND JOURNAL of MEDICINE
ORIGINAL ARTICLE
Talquetamab-Daratumumab in Relapsed
or Refractory Myeloma
R. Mina, 1,2 M. Beksac,³ P. Rodríguez-Otero, 4 W. Chen,⁵ M.-V. Mateos, 6 J. Li,⁷
P. Moreau, 8 Y.C. Cohen, 9,10 C.-K. Min, 11 T. Jelinek, 12 J.C. Ye, 13 H. Magen, 14,15
S.M. Rubinstein, 16 W. Fu, 17 V. Hungria, 18 G. Cengiz Seval, 19 J.S. Farias,20
J. Radocha, 21 S. Maral, 22 M. Turgut, 23 Y. Koh, 24 D. O'Leary, 25 J. Schmidt Filho, 26
R. Thertulien, 27 G. An, 28 S.-Y. Huang, 29 S. Grosicki, 30 A. Tyczyńska, 31 R. Banerjee,32
M.J. Pianko, 33 J. Martínez-López, 34 P. Steckiewicz, 35 D. Maruyama,³⁶
K. Fukushima, 37 A. Oriol, 38 J. Lopez Pardo, 39 H. Goldschmidt, 40 C. Pawlyn, 41,42
A. Perrot, 43 E. Zamagni, 44 M.A. Dimopoulos, 45,46 L. Rasche, 47 J. Tolbert,⁴
W. Terry, 48 C. Courtoux, 48 X. Liu, 49 S.Y. Vasey, 48 K. Connors, 50 M. Festa, 51
C. Heuck,⁴⁸ A. Langlois, 48 L. O'Rourke, 48 J. Zhou, 48 X. Qin, 48 J. Lu, 52 J. Gong,48
D. Vieyra, 48 and P.M. Voorhees, 53 for the MonumenTAL-3 Investigators*
MonumenTAL-3 is a Phase 3, randomized study evaluating talquetamab (a first-in-class GPRC5D×CD3 bispecific antibody) in combination with daratumumab, with or without pomalidomide (Tal-DP and Tal-D), versus the standard regimen of daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed or refractory multiple myeloma. Results were presented at the 2026 EHA Congress (Abstract S100) with simultaneous publication in The New England Journal of Medicine — the first Phase 3 study to demonstrate superior progression-free survival with a GPRC5D bispecific combination in earlier-line myeloma. The talquetamab combinations are investigational and not FDA-approved (talquetamab monotherapy is approved for adults with RRMM after ≥4 prior lines of therapy).
Phase 3, open-label, randomized 1:1:1 to Tal-DP, Tal-D or DPd. Primary endpoint: PFS by independent review committee. (NEJM, S100)
Population
864 patients with RRMM and ≥1 prior line including lenalidomide and a proteasome inhibitor; 85.1% lenalidomide-refractory; 30.9% high-risk cytogenetics. (NEJM, S100)
Both talquetamab combinations significantly improved PFS versus DPd. 24-month PFS was 81.3% (Tal-DP) and 77.6% (Tal-D) versus 51.2% (DPd), with hazard ratios of 0.28 (Tal-DP) and 0.33 (Tal-D), both P<0.0001. (NEJM, S100)
A clinically meaningful OS benefit was observed: 24-month OS was 89.2% (Tal-DP) and 87.9% (Tal-D) versus 79.1% (DPd), with OS hazard ratios of 0.47 (Tal-DP, P=0.0006) and 0.51 (Tal-D, P=0.0015). Response was deep: ≥CR rates were 71.1% / 68.9% vs 34.5%, and MRD-negative ≥CR 52.3% / 46.3% vs 15.9%. (NEJM, S100)
Adverse events were consistent with each agent. GPRC5D-related events were common — taste changes (~73–75%) and decreased weight (~38–46%), most grade 1–2. Ataxia/balance disorders occurred with the talquetamab arms (Tal-DP 11.6% grade 1–2, 2.9% grade 3) and were primarily low grade. CRS was mostly grade 1–2. Grade 3–4 TEAEs and infections were higher with Tal-DP. (NEJM, S100)
⚠️ Investigational. MonumenTAL-3 is the first Phase 3 study to show a GPRC5D bispecific antibody combination outperforming standard DPd in earlier-line relapsed/refractory myeloma. KOLs flagged the practice-changing efficacy balanced against GPRC5D-specific toxicity (taste changes, weight loss, late-onset ataxia). The talquetamab combinations are not FDA-approved.
