J&J Medical Connect
TALVEY®

(talquetamab-tgvs)

J&J Medical Connect

Connect with us

  • Products

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

TALVEY® (talquetamab-tgvs)

Medical Information

TALVEY - Occurrence and Management of Cytokine Release Syndrome (CRS)

Last Updated: 02/10/2026

SUMMARY

  • Johnson & Johnson does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
  • This response provides relevant data from company-sponsored clinical trials, and the content is limited to the studies included below.
  • Please refer to local labeling for recommended pre-treatment medications to reduce the risk of CRS and CRS management recommendations.
  • Consider further management per current practice guidelines or institutional guidelines.
  • MonumenTAL-1 is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).1 
    • van de Donk (2025)2 published the incidence and management of CRS in patients treated with TALVEY in the MonumenTAL-1 study.
    • Rasche et al (2025)3 presented the incidence of CRS from the MonumenTAL-1 study at an extended median follow-up of 38.2 months for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 31.2 months for the 0.8 mg/kg SC every other week (Q2W) cohort, and 30.3 months for the prior T-cell redirection therapy (TCR)-exposed (QW and Q2W) cohorts.
    • Schinke et al (2024)4 reported findings from the MonumenTAL-1 study on the effects of prophylactic tocilizumab in mitigating CRS following TALVEY treatment, with a median follow-up of 4.4 months. The use of prophylactic tocilizumab and post-dose dexamethasone appeared to reduce both the incidence and severity of CRS across different levels of disease burden.
    • Morillo et al (2024)5 evaluated the impact of reduced number of step-up doses (steps) of TALVEY (0.8 mg/kg Q2W) on CRS parameters by comparing two alternative TALVEY Q2W SUD cohorts (group 1: n=6; group 2: n=12) with the global cohort receiving 0.8 mg/kg Q2W TALVEY (N=154) at a median follow-up of 6.7 months.
    • The prophylactic tocilizumab cohort is evaluating the administration of intravenous (IV) tocilizumab (8 mg/kg IV) prior to TALVEY to mitigate CRS in 27 patients with RRMM.6
      • Dytfeld et al (2025)6 presented the incidence of CRS in the prophylactic tocilizumab cohort at a median follow-up of 4.4 months.
  • MonumenTAL-2 is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with multiple myeloma (MM).7-9
    • Cohort D is evaluating the efficacy and safety of TALVEY + DARZALEX FASPRO® (daratumumab hyaluronidase) and lenalidomide in 34 patients with newly diagnosed multiple myeloma (NDMM).9
      • Nooka et al (2024)9 presented the incidence of CRS of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months and the TALVEY 0.8 mg/kg every 4 weeks (Q4W) + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months.
    • Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.7
      • Quach et al (2025)7 presented the incidence of CRS from the TALVEY + pomalidomide cohort of the MonumenTAL-2 study at a longer median follow-up of 20.7 months.
  • RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI® (teclistamab-cqyv) in patients with RRMM, including those with extramedullary disease (EMD).10-13 
    • Usmani et al (2025)10 presented the incidence of CRS from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD at a median follow-up of 16.8 months.
    • Kumar et al (2025)11 published the incidence of CRS from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD at a median follow-up of 12.6 months.
    • Mateos et al (2025)12 presented the incidence of CRS from phase 1b of the RedirecTT-1 study across all dose levels (dose levels 1-5) at a median follow up of 38 months, in patients with RRMM, including those with EMD.
    • Cohen et al (2025)13 published the incidence of CRS from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months in the all dose levels (dose levels 1-5) cohort.
  • TRIMM-2 is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO regimens + TECVAYLI or TALVEY in patients with RRMM.14-16
    • Chari et al (2025)15 published the incidence of CRS in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohorts at a median follow-up of 18.6 months (range, 1.2-39.1).
    • Bahlis et al (2024)14presented the incidence of CRS of the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts at a median follow-up of 15.8 months and 17.5 months, respectively.
  • TRIMM-3 is a phase 1b, nonrandomized, open-label study evaluating the dosing, safety, and tolerability of a programmed cell death receptor-1 (PD-1) inhibitor in combination with TALVEY or TECVAYLI in patients with RRMM.17,18 
    • Perrot et al (2025)17 presented the incidence of CRS of the TALVEY + cetrelimab cohort at a median follow-up of 11.5 months.

PRODUCT LABELING

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.1

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 4 cohorts:

  • TCR naive: 0.4 mg/kg SC QW, not previously exposed to TCR such as chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAbs; prior BCMA antibody-drug conjugate [ADC] allowed).19,20
  • TCR naive: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).19,20
  • TCR exposed: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W, have been previously exposed to TCRs.19,20
    • Among the prior TCR-exposed cohort, patients were divided based on type of TCR (CAR-T, BsAb, or CAR-T and BsAb).
  • Prophylactic tocilizumab: 0.8 mg/kg SC Q2W; tocilizumab 8 mg/kg IV prior to the first SUD of TALVEY to mitigate CRS.6
  • Key eligibility criteria1:
    • ≥18 years of age, measurable MM per International Myeloma Working Group (IMWG) criteria.
    • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb.
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.
  • Dosing1:
    • SUDs of TALVEY were administered as follows for TCR naive and exposed cohorts1:
      • 0.4 mg/kg SC QW: 0.01 mg/kg, and 0.06 mg/kg.
      • 0.8 mg/kg SC Q2W: 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg. 
      • Subsequent treatment doses: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W until disease progression, unacceptable toxic effects, withdrawal of consent, or end of study.1
    • Prophylactic tocilizumab cohort: single-dose 8 mg/kg IV tocilizumab approximately 3 hours before of administering TALVEY SUD 1; SUDs of TALVEY were administered at a dose 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg or 0.4 mg/kg SC followed by subsequent treatment doses of TALVEY at 0.8 mg/kg Q2W.6 
  • Premedications/Postmedications
    • TCR naive and TCR exposed cohorts: glucocorticoid (dexamethasone 16 mg or equivalent), antihistamine, and antipyretic were required to be administered before each SUD, and for the first full treatment dose of TALVEY.1
    • Prophylactic tocilizumab cohort: single 8mg/kg IV tocilizumab dose along with required pretreatments of glucocorticoid, antihistamine, and antipyretic before the first SUD of TALVEY; 8 mg dexamethasone by mouth (PO)/IV administered daily for 2 days after each SUD and first full treatment dose of TALVEY.6
  • For the TCR naive and exposed cohorts, patients were required to be hospitalized for at least 48 hours from the start of each SUD and the first full treatment dose of TALVEY.1
  • For the prophylactic tocilizumab cohort, patients could be treated on an inpatient or outpatient basis.6

van de Donk (2025)2,21 published a detailed overview of the incidence and management of CRS in patients treated with TALVEY in the MonumenTAL-1 study.

Study Design/Methods

  • Patients from phase 1 and phase 2 of MonumenTAL-1 study who received TALVEY 0.4 mg/kg QW, TALVEY 0.4 mg/kg Q2W, and TALVEY 0.4 mg/kg Q4W (n=213) and TALVEY 0.8 mg/kg QW, TALVEY 0.8 mg/kg Q2W, and TALVEY 0.8 mg/kg Q4W (n=217), respectively, were included in this interval analysis.
  • Samples were collected prior to the first SUD and after select full-treatment doses.
  • Maximum fold change of cytokine induction and T-cell activation was defined as the maximum increase fold change per patient from baseline up to cycle 2 day 1.

CRS Management and Grading

  • Prior to administration of TALVEY, complete resolution of CRS (including fever) and absence of evidence for serious infections (including bacterial, viral, or fungal infections) was required.
  • CRS revised grading system criteria were mapped to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Results

Patient Characteristics

  • As of January 17, 2023, 288 TCR naïve patients and 51 TCR exposed patients were included in the study.
    • Out of 288 TCR naïve patients, 143 patients received TALVEY 0.4 mg/kg QW at a median follow-up of 18.8 months and 145 patients received TALVEY 0.8 mg/kg Q2W at a median follow-up of 12.7 months.
    • Out of 51 TCR exposed patients, 43 patients received TALVEY 0.4 mg/kg QW and 8 patients received TALVEY 0.8 mg/kg Q2W at a median follow-up of 14.8 months.
      • Out of 51 TCR exposed patients, 36 patients received CAR-T therapy, 18 patients received a BsAb (94% of patients received BCMA-targeted therapy), and 3 patients received both CAR-T therapy and BsAbs.
  • Excluding patients who received additional SUDs (ie, repeat step-up dosing) before the first full dose in cycle 1, median time between SUDs were:
    • TALVEY 0.4 mg/kg QW cohort: 2.8 days (range, 1-7) for SUD dose 1 to 2; 3 days (range, 1-8) for SUD dose 2 to cycle 1 day 1.
    • TALVEY 0.8 mg/kg Q2W cohort: 2.0 days (range, 1-8) for SUD 1 to 2; 2.9 days (range 1-7) for SUD dose 2 to 3; 2.9 days (range, 1-2) for SUD 3 to cycle 1 day 1.

Incidence, Timing, and Severity of CRS

  • Incidence and severity of CRS is presented in Tables: MonumenTAL-1 Study: Overall Incidence and Severity of CRS and MonumenTAL-1 Study: Incidence of CRS Over Time.
  • The most frequent symptoms were pyrexia (73.8%-79.0%), followed by hypotension (13.8%-21.6%) and chills (9.1%-17.6%).
  • In the prior TCR-exposed cohort (n=36), CRS was reported in 75.0% of patients with prior CAR-T therapy (grade 1, 55.6%; grade 2, 16.7%; grade 3, 2.0%) and in 72.2% of those with prior BsAb therapy (n=18; grade 1, 44.4%; grade 2, 27.8%).
  • All CRS events resolved, except one fatal infection-related case in the TALVEY 0.4 mg/kg QW cohort.
  • Most repeat SUDs were administered after the first full dose, occurring primarily at cycle 5+ in TALVEY 0.4 mg/kg QW cohort, cycles 3-5+ in TALVEY 0.8 mg/kg Q2W cohorts, and cycles 1-2 in prior TCR-exposed cohort. The median interval between the last dose and the repeat SUD ranged from 40 to 61 days across cohorts.

MonumenTAL-1 Study: Overall Incidence and Severity of CRS2
Parameter
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=145)
Prior TCR
(n=51)
Number of patients with CRS, n (%)
113 (79.0)
108 (74.5)
39 (76.5)
Maximum toxicity grade, n (%)
   Grade 1
89 (62.2)
83 (57.2)
27 (52.9)
   Grade 2
21 (14.7)
24 (16.6)
11 (21.6)
   Grade 3
3 (2.1)
1 (0.7)
1 (2.0)
   Grade 4/5
0
0
0
Patients with serious CRSa, n (%)
24 (16.8)
15 (10.3)
6 (11.8)
Discontinuation due to CRS, n (%)
0
1 (0.7)
0
Median time to onsetb,c,
hours (range)
25.9 (1.3-165.0)
28.0 (0.1-333.4)
26.3 (4.9-97.2)
Median durationc, hours (range)
14.5 (0.5-221.6)
18.0 (0.0-621.8)
20.4 (0.9-71.5)
Patients with CRS up to 1st full dose, n (%)
   1st SUD
48 (33.6)
38 (26.2)
12 (23.5)
   2nd SUD
70 (49.0)
59 (40.7)
21 (41.2)
   3rd SUD
NA
50 (34.5)
1 (2.0)
   1st full dose
38 (26.6)
19 (13.1)
17 (33.3)
Patients with CRS during cycle ≥ 2, n (%)
5 (3.5)
5 (3.4)
2 (3.9)
Patients with CRS during repeat SUDsd, n (%)
0
3 (10.7)
1 (20.0)
Patients with 1st CRS up to 1st full dose, n (%)
   1st SUD
48 (33.6)
38 (26.2)
12 (23.5)
   2nd SUD
53 (37.1)
39 (26.9)
16 (31.4)
   3rd SUD
NA
22 (15.2)
0
   1st full dose
8 (5.6)
5 (3.4)
11 (21.6)
Patients with 1st CRS during cycle ≥ 2, n (%)
0
3 (2.1)
0
Repeat step-up for 1st CRS, n (%)
0
0
0
Average inpatient stay, days (range)
7.5 (2-36)
9.0 (2-20)
8.0 (2-19)
Patients who received supportive measurese, n (%)
106 (74.1)
103 (71.0)
39 (76.5)
   Tocilizumabf
50 (35.0)
55 (37.9)
26 (51.0)
   Corticosteroids
5 (3.5)
5 (3.4)
8 (15.7)
   Oxygeng
8 (5.6)
10 (6.9)
3 (5.9)
   Nasal cannula low flow (≤ 6 L/min)
8 (5.6)
9 (6.2)
2 (3.9)
   Face mask
0
0
1 (2.0)
   Venturi mask
1 (0.7)
0
0
   Other
0
1 (0.7)
0
   Vasopressor
2 (1.4)
1 (0.7)
1 (2.0)
Patients with > 1 CRS event, n (%)
46 (32.2)
46 (31.7)
13 (25.5)
Grade worsened at any subsequent event, n (%)
6 (4.2)
6 (4.1)
3 (5.9)
CRS with infections, n (%)
3 (2.7)
 9 (8.3)
0
CRS with neutropenia, n (%)
9 (8)
2 (1.9)
3 (7.7)
Abbreviations: CRS, cytokine release syndrome; N/A, not applicable; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.
aDefined as admission to an inpatient facility or extension of a current hospitalization for > 24 hours.
bIn relation to the most recent administered dose.
cCalculated only in phase 2 patients (timing was not uniformly collected in phase 1); n=141, 140, and 36, respectively, for time to onset, and n = 139, 138, and 36 for duration of CRS in the TALVEY 0.4 mg/kg QW, TALVEY 0.8 mg/kg Q2W, and prior TCR-exposed cohorts, respectively.
dCalculated based on patients who received repeat step-up dosing (TALVEY 0.4 mg/kg QW, n=8; TALVEY 0.8 mg/kg Q2W, n=28; prior TCR-exposed, n=5).
ePatients could receive >1 supportive therapy.
fTocilizumab was allowed for all CRS events; the protocol prohibited prophylactic tocilizumab use.
gPrimarily low flow.

MonumenTAL-1 Study: Incidence of CRS Over Time2
Patients With CRS Events, n (%)
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=145)
Prior TCR
(n=51)
Total patients with CRS
113 (79.0)
108 (74.5)
39 (76.5)
Grade 1 CRS
   SUD 1
41 (28.7)
33 (22.8)
9 (17.6)
   SUD 2
59 (41.3)
48 (33.1)
15 (29.4)
   SUD 3
NA
45 (31.0)
0
   Cycle 1 day 1
34 (23.8)
16 (11.0)
13 (25.5)
   Cycle 1 day 8
5 (3.5)
NA
1 (2.0)
   Cycle 1 day 15
2 (1.4)
7 (4.8)
0
   Cycle 1 day 22
6 (4.2)
NA
0
   Cycle ≥ 2
5 (3.5)
5 (3.4)
2 (3.9)
   Repeat step-up
0
3 (2.1)
1 (2.0)
Grade 2 CRS
   SUD 1
7 (4.9)
7 (4.8)
4 (7.8)
   SUD 2
12 (8.4)
12 (8.3)
6 (11.8)
   SUD 3
NA
4 (2.8)
1 (2.0)
   Cycle 1 day 1
5 (3.5)
3 (2.1)
3 (5.9)
   Cycle 1 day 8
0
NA
0
   Cycle 1 day 15
0
0
0
   Cycle 1 day 22
0
NA
0
   Cycle ≥ 2
0
0
0
   Repeat step-up
0
0
0
Grade 3 CRS
   SUD 1
0
0
0
   SUD 2
1 (0.7)
0
0
   SUD 3
NA
1 (0.7)
0
   Cycle 1 day 1
1 (0.7)
0
1 (2.0)
   Cycle 1 day 8
1 (0.7)
NA
0
   Cycle 1 day 15
0
0
0
   Cycle 1 day 22
0
NA
0
   Cycle ≥ 2
0
0
0
   Repeat step-up
0
0
0
Abbreviations: CRS, cytokine release syndrome; NA, not applicable; Q2W, every 2 weeks; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy.

CRS During Repeat Step-up Dosing

  • Repeat SUDs were administered to 5.6% of patients (n=8) in the TALVEY 0.4 mg/kg QW cohort, 19.3% of patients (n=28) in the TALVEY 0.8 mg/kg Q2W cohort, and 9.8% of patients (n=5) in the prior TCR-exposed cohort, as recommended following a dose hold or delay.
  • Most repeat SUDs occurred after the 1st full dose (majority at cycle 5+ in TALVEY 0.4 mg/kg QW, cycles 3-5+ in TALVEY 0.8 mg/kg Q2W, and cycles 1-2 in prior TCR-exposed cohort); median time between last dose received and repeat SUDs was 40-61 days across cohorts.

CRS After Prolonged Dosing Intervals

  • Among 213 patients receiving TALVEY 0.4 mg/kg QW, Q2W, or Q4W dosing, 2.8% of patients (n = 6) experienced grade 1 CRS when treatment was restarted at the full dose after an interval of ≤28 days; no CRS occurred when treatment was restarted at SUD 2 after an interval of 29-56 days.
  • Among 217 patients receiving TALVEY 0.8 mg/kg QW, Q2W, or Q4W, 7.8% of patients (n = 17) experienced grade 1 CRS when treatment was restarted at the full dose after an interval of ≤63 days; no patients restarted beyond day 63.
  • At the 0.8 mg/kg dose, pharmacokinetic (PK) analysis evaluated the association between serum concentration and CRS risk following restart at the full dose.
  • Of the 8 evaluable patients, 2 patients developed grade 1 CRS with serum concentrations below the FDA-recommended PK threshold, while 6 patients did not develop CRS (3 patients had serum concentrations below and 3 patients had serum concentrations above the threshold).
  • No PK data were available for the 0.4 mg/kg dose.

Recurrent CRS Events

  • Recurrent CRS was reported in 32.2% of patients in the TALVEY 0.4 mg/kg QW cohort, 31.7% of patients in the TALVEY 0.8 mg/kg Q2W cohort, and 25.5% of patients in the prior TCR-exposed cohort.
  • Most recurrent events occurred during step-up dosing (11.9%, 15.0%, and 9.8%) or on C1D1 (21.0%, 10.5%, and 11.8%), with fewer events after cycle 1 day 1 (11.2%, 5.5%, and 5.9%) in the TALVEY 0.4 mg/kg QW, the TALVEY 0.8 mg/kg Q2W, and in the prior TCR-exposed cohorts, respectively.
  • Median time to onset of recurrent CRS was 26–29 hours after the last TALVEY dose.
  • Worsening CRS at subsequent events was observed in 4.2% of patients in the TALVEY 0.4 mg/kg QW, 4.1% patients in the TALVEY 0.8 mg/kg Q2W cohort, and 5.9% of patients in the prior TCR-exposed cohort.
  • Most CRS events after cycle 1 day 8 occurred in patients who had prior CRS during step-up or cycle 1 day 1 dosing; these were predominantly grade 1, except for one grade 3 event after cycle 1 day 8, which coincided with bacteremia.

Management of CRS


MonumenTAL-1 Study: Patients Receiving Tocilizumab and/or Corticosteroids for Treatment-Emergent CRS21 
Parameter
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=145)
Prior TCR
(n=51)
Patients with CRS, n (%)
113 (79.0)
108 (74.5)
39 (76.5)
Patients who received tocilizumab but no corticosteroidsa, n (%)
48 (33.6)
50 (34.5)
23 (45.1)
Patients who received corticosteroids but no tocilizumaba, n (%)
2 (1.4)
2 (1.4)
5 (9.8)
Patients who received both tocilizumab and corticosteroidsa,
n (%)
3 (2.1)
5 (3.4)
4 (7.8)
Number of CRS events, n
189
189
57
   CRS events treated only with
   tocilizumab, n (%)
56 (29.6)
60 (31.7)
27 (47.4)
      Grade 1
40 (21.2)
46 (24.3)
20 (35.1)
      Grade 2
15 (7.9)
14 (7.4)
7 (12.3)
      Grade 3
1 (0.5)
0
0
   CRS events treated only with
   corticosteroids, n (%)
2 (1.1)
2 (1.1)
6 (10.5)
      Grade 1
2 (1.1)
2 (1.1)
2 (3.5)
      Grade 2
0
0
4 (7.0)
   CRS events treated with both
   tocilizumab and corticosteroids, n %)
5 (2.6)
6 (3.2)
4 (7.0)
      Grade 1
2 (1.1)
3 (1.6)
1 (1.8)
      Grade 2
2 (1.1)
2 (1.1)
2 (3.5)
      Grade 3
1 (0.5)
1 (0.5)
1 (1.8)
Abbreviations: CRS, cytokine release syndrome; Q2W, every 2 weeks; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.
aFor ≥1 event of CRS.

MonumenTAL-1 Study: Subsequent CRS Events Based on the Use of Tocilizumab for first CRS Event2
Parameter
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=145)
Prior TCR
(n=51)
≥1 subsequent CRS event based on use of tocilizumab for first CRS event, n/N (%)
   Tocilizumab useda
7/43 (16.3)
8/44 (18.2)
5/21 (23.8)
   Tocilizumab not usedb
39/70 (55.7)
38/64 (59.4)
8/18 (44.4)
Abbreviations: CRS, cytokine release syndrome; Q2W, every 2 weeks; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.
aNumber of patients who experienced ≥1 subsequent CRS event after receiving tocilizumab for their 1st CRS event/total number of patients in the cohort who received tocilizumab for their 1st CRS event.
bNumber of patients who experienced ≥1 subsequent CRS event after not receiving tocilizumab for their 1st CRS event/total number of patients in the cohort who did not receive tocilizumab for their 1st CRS event.

MonumenTAL-1 Study: Tocilizumab Doses by Cohort2
Parameter
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=145)
Prior TCR
(n=51)
Number of tocilizumab doses, n (%)
   1 Dose
44 (30.8)
52 (35.9)
25 (49.0)
   2 Doses
5 (3.5)
3 (2.1)
1 (2.0)
   3 Doses
1 (0.7)
0
0
Abbreviations: Q2W, every 2 weeks; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.

Impact on Efficacy


MonumenTAL-1 Study: Efficacy Outcomes in Patients With and Without CRS2
Response Type
0.4 mg/kg QW
0.8 mg/kg Q2W
Prior TCR
With CRS
(n=113)
Without CRS
(n=30)
With CRS
(n=108)
Without CRS
(n=37)
With CRS
(n=39)
Without CRS
(n=12)
ORR, n (%)
86 (76.1)
20 (66.7)
81 (75.0)
23 (62.2)
25 (64.1)
8 (66.7)
   PR, %
15
13.3
10.2
13.5
7.7
16.7
   VGPR, %
29.2
13.3
23.1
18.9
17.9
25
   CR, %
9.7
10
9.3
8.1
5.1
8.3
   sCR, %
22.1
30
32.4
21.6
33.3
16.7
Median PFSa,
months (95% CI)
7.6
(5.7-9.9)
7.5
(4.4-NE)
14.2
(9.6-NE)
11.3
(2.5-NE)
5.0
(3.4-13.8)
5.1
(0.9-13.0)
Abbreviations: CI, confidence interval; CR, complete response; CRS, cytokine release syndrome; NE, not estimable; ORR, overall response rate; PFS, progression-free survival; PR, partial response; Q2W, every 2 weeks; QW, weekly; sCR, stringent complete response; TCR, T-cell redirection therapy; VGPR, very good partial response.
aPFS estimates were not mature in the TALVEY 0.8 mg/kg Q2W and prior TCR-exposed cohorts.

MonumenTAL-1 Study: Efficacy Outcomes in Patients Treated With or Without Tocilizumab2
Category
0.4 mg/kg QW
0.8 mg/kg Q2W
Prior TCR
With Tocilizumab
(n=50)
Without Tocilizumab
(n=63)
With Tocilizumab
(n=55)
Without Tocilizumab
(n=53)
With Tocilizumab
(n=26)
Without Tocilizumab
(n=13)
ORR, n (%); 95% CI
35 (70.0); 55.4-82.1
51 (81.0); 69.1-89.8
40 (72.7); 59.0-83.9
41 (77.4); 63.8-87.7
15 (57.7); 36.9-76.6
10 (76.9); 46.2-95.0
   PR, %
16
14.3
12.7
7.5
3.8
15.4
   VGPR, %
30
28.6
23.6
22.6
23.1
7.7
   CR, %
4
14.3
7.3
11.3
7.7
-
   sCR, %
20
23.8
29.1
35.8
23.1
53.8
Median PFSa, months
(95% CI)
8.5
(6.7-12.1)
6.3
(4.9-7.7)
NE
(14.2-NE)
11.9
(7.0-NE)
12.3
(3.8-NE)
3.9
(3.4-7.7)
Abbreviations: CI, confidence interval; CR, complete response; NE, not estimable; ORR, overall response rate; PFS, progression-free survival; PR, partial response; Q2W, every 2 weeks; QW, weekly; sCR, stringent complete response; TCR, T-cell redirection therapy; VGPR, very good partial response.
aPFS estimates were not mature in the TALVEY 0.8 mg/kg Q2W and prior TCR-exposed cohorts.

MonumenTAL-1 Study: Efficacy Outcomes in Patients Treated With or Without Corticosteroids2
Response
0.4 mg/kg QW
0.8 mg/kg Q2W
Prior TCR
With Steroids
(n=5)
Without Steroids
(n=108)
With Steroids
(n=5)
Without Steroids
(n=103)
With Steroids
(n=8)
Without Steroids
(n=31)
ORR, n (%); 95% CI
3 (60.0); 14.7-94.7
83 (76.9); 67.8-84.4
5 (100); 47.8-100.0
76 (73.8); 64.2-82.0
7 (87.5); 47.3-99.7
18 (58.1); 39.1-75.5
   PR, %
-
15.7
0
10.7
12.5
 6.5
   VGPR, %
40
28.7
0
24.3
25.0
16.1
   CR, %
-
10.2
20
8.7
0
6.5
   sCR, %
20
22.2
80
30.1
50.0
29.0
Abbreviations: CI, confidence interval; CR, complete response; ORR, overall response rate; PR, partial response; Q2W, every 2 weeks; QW, weekly; sCR, stringent complete response; TCR, T-cell redirection therapy; VGPR, very good partial response

Rasche et al (2025)3 presented the incidence of CRS from the MonumenTAL-1 study at an extended median follow-up of 38.2 months for the 0.4 mg/kg SC QW cohort, 31.2 months for the 0.8 mg/kg SC Q2W cohort, and 30.3 months for the prior TCR-exposed (QW and Q2W) cohorts.

Safety Results


MonumenTAL-1 Study: Summary of CRS Events3
AE (≥30%), n (%)
0.4 mg/kg SC QW
(n=143)
0.8 mg/kg SC Q2W
(n=154)
Prior TCR QW and Q2W
(n=78)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
CRS
113 (79.0)
3 (2.1)
116 (75.3)
1 (0.6)
57 (73.1)
1 (1.3)
Abbreviations: AE, adverse event; CRS, cytokine release syndrome; Q2W, every other week; QW, weekly; SC, subcutaneous; TCR, T-cell redirection therapy.
Clinical data cutoff date of September 2024.

Schinke et al (2024)4 presented findings from the MonumenTAL-1 study on the effects of prophylactic tocilizumab in mitigating CRS following TALVEY treatment at a median duration of follow-up of 4.4 months (range, 0.3-8.8).

Safety Results

Baseline Characteristics


MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): Baseline Characteristics4
Characteristic
Prophylactic Tocilizumab
(N=12)
Age, years, median (range)
69 (51-77)
   Male, n (%)
9 (75.0)
Race, n (%)
   White
7 (58.3)
   Black or African American
5 (41.7)
ECOG PS, n (%)
   0
4 (33.3)
   1
7 (58.3)
   2
1 (8.3)
Extramedullary plasmacytomas, n (%)
   0
11 (91.7)
   ≥1
1 (8.3)
High-risk cytogeneticsa,n (%)
2 (20.0)
ISS stageb,n (%)
   I
6 (50.0)
   II
5 (41.7)
   III
1 (8.3)
Prior LOT, median (range)
3 (3-10)
Refractory status, n (%)
   Triple-classc
6 (50.0)
   Penta-drugd
1 (8.3)
   To last LOT
11 (91.7)
% BMPCs (biopsy or aspirate)e, n (%)
   <5
5 (41.7)
   ≥5 to ≤30
2 (16.7)
   >30 to <60
2 (16.7)
   ≥60
3 (25.0)
Abbreviations: BMPC, bone marrow plasma cell; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ISS, International Staging System; LOT, line of therapy; mAb, monoclonal antibody; PI, proteasome inhibitor.
aDefined as del(17p), t(4;14), and/or t(14;16); calculated from n=10.
bISS staging is derived based on serum β2-microglobulin and albumin.
c≥1 PI, ≥1 immunomodulatory drugs, and ≥1 anti-CD38 mAb.
d≥2 PIs, ≥2 immunomodulatory drugs, and ≥1 anti-CD38 mAb.
eMaximum value from bone marrow biopsy or bone marrow aspirate is selected if both the results are available.

CRS Incidence, Severity, Timing, and Treatment


MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): Incidence of CRS in the Prophylactic Tocilizumab Cohort4
CRS (%)
Global 0.8 mg/kg Q2W
Prophylactic Tocilizumab
Grade 1
57.8
16.7
Grade 2
16.2
-
Grade 3
0.6
-
Abbreviations: CRS, cytokine release syndrome, Q2W, every other week.

MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): Baseline Characteristics of Patients With and Without CRS4
Characteristic, n
No CRS
(n=9)
CRS During SUD Through Cycle 1
(n=2a)
% BMPCs
   <5
4
1
   ≥5 to ≤30
2
-
   >30 to <60
2
-
   ≥60
1
1
ISS stage
   I
4
1
   II
4
1
   III
1
-
EMD status
   Yes
1
-
   No
8
2
Abbreviations: BMPC, bone marrow plasma cell; CRS, cytokine release syndrome; EMD, extramedullary disease; ISS, International Staging System; SUD, step-up dose.
aPatient with CRS at cycle 2 day 1 had the following baseline characteristics: ≥60% BMPCs; ISS stage I; no EMD.

Morillo et al (2024)5 presented the impact of fewer SUDs on CRS parameters, in the alternative TALVEY Q2W SUD and global TALVEY 0.8 mg/kg Q2W cohorts at a median duration of follow-up of 6.7 months (range, 2.2-9.9).

Results

Treatment Disposition

  • In MonumenTAL-1, alternative SUD groups were added to the 0.8 mg/kg Q2W schedule.
  • A total of 18 patients were included in this analysis to evaluate alternative TALVEY Q2W SUD regimens.
    • Group 1 (n=6): week 1 SUD of TALVEY (0.03 mg/kg and 0.2 mg/kg SC); cycle 1, day 1 of TALVEY (0.8 mg/kg SC Q2W).
    • Group 2 (n=12): week 1 SUD of TALVEY (0.06 mg/kg and 0.4 mg/kg SC); cycle 1, day 1 of TALVEY (0.8 mg/kg SC Q2W).
    • Patients in both group 1 and 2 could switch to 0.8 mg/kg Q4W at confirmed partial response or better (≥PR).

Safety

CRS Incidence, Severity, Timing, and Treatment

MonumenTAL-1 Study: Summary of CRS Events in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts5
CRS Eventa
Global
0.8 mg/kg Q2W
Cohort
(N=154)
Alternative TALVEY Q2W SUD Cohorts
Group 1
0.8 mg/kg Q2W
Cohort
(n=6)
Group 2
0.8 mg/kg Q2W
Cohort
(n=12)
CRS events, n (%)
-
6 (100)
11 (91.7)
Multiple CRS events, n (%)
51 (33.1)
1 (16.7)
3 (25.0)
Cycle with highest CRS events,
SUD cycle (%)
2 (40.9)
2 (66.7)
1 (75)
   CRS events during cycle 1, n
22
1
1
   CRS events after cycle 2, n
5
1
1
Median time to CRS onset, days
2
2
2
Median duration of CRS, days
2
2
2
Abbreviations: CRS, cytokine release syndrome; Q2W, every other week; SUD, step-up dose.
aCRS was graded by Lee et al criteria.

MonumenTAL-1 Study: CRS Incidence and Severity in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts5
AE, %
Global
0.8 mg/kg Q2W Cohort
(N=154)
Alternative TALVEY Q2W SUD Cohorts
Group 1
0.8 mg/kg Q2W Cohort
(n=6)
Group 2
0.8 mg/kg Q2W Cohort
(n=12)
Grade 1
Grade 2
Grade 3
Grade 1
Grade 2
Grade 3
Grade 1
Grade 2
Grade 3
CRSa
57.8
16.2
0.6
50.0
50.0
0
58.3
33.3
0
Abbreviations: AE, adverse event; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; Q2W, every other week; SUD, step-up dose.
aCRS was graded by Lee et al criteria.

MonumenTAL-1 Study: CRS Timing in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts5
Global Q2W Cohort (N=154)
AE, n (%)
0.01 mg/kg SUD
0.06 mg/kg SUD
0.4 mg/kg SUD
C1D1 (0.8 mg/kg)
CRSa
41 (26.6)
63 (40.9)
56 (36.4)
22 (14.3)
Group 1 (n=6)
AE, n (%)
NA
0.03 mg/kg SUD
0.2 mg/kg SUD
C1D1 (0.8 mg/kg)
CRSa
NA
3 (50.0)
4 (66.7)
0
Group 2 (n=12)
AE, n (%)
NA
0.06 mg/kg SUD
0.4 mg/kg SUD
C1D1 (0.8 mg/kg)
CRSa
NA
9 (75.0)
5 (41.7)
1 (8.3)
Abbreviations: AE, adverse event; C1D1, cycle 1 day 1; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; NA, not applicable; Q2W, every other week; SUD, step-up dose.
aCRS was graded by Lee et al criteria.

Prophylactic Tocilizumab Cohort Safety Results

Dytfeld et al (2025)6 presented the incidence of CRS in the prophylactic tocilizumab cohort at a median follow-up of 4.4 months (range, 0.5-18.4).

Safety Results


MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): CRS Events6
Parameter
Prophylactic Tocilizumab
(N=27)
CRSa, n (%)
   Grade 1
5 (18.5)
   Grade 2
0 (0)
   Grade 3
0 (0)
Onset of CRSb, days, median (range)
2.5 (2.0-12.0)
Duration of CRS, days, median (range)
1.0 (1.0-6.0)
Supportive measures for CRSc, n (%)
4 (14.8)
   Tocilizumab
3 (11.1)
   Oxygen
0 (0)
   Corticosteroids
0 (0)
   Paracetamol
3 (11.1)
   Other
1 (3.7)
CRS recovered or resolvedd, n (%)
6 (100.0)
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome.
aCRS was graded by ASTCT criteria.
bRelative to the most recent dose.
cPatients could receive ≥1 supportive therapy.
dPatients could have ≥1 event.

MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): CRS Events in Inpatient and Outpatient Settings6
Parameter
Inpatient
(n=10)
Outpatient
(n=17)
CRSa, n (%)
3 (30.0)
2 (11.8)b
   Grade 1
3 (30.0)
2 (11.8)b
   Grade 2
0 (0)
0 (0)
   Grade 3
0 (0)
0 (0)
Onset of CRSc, days, median (range)
2.0 (2.0-12.0)
5.5 (3.0-8.0)
Duration of CRS, days, median (range)
1.0 (1.0-6.0)
2.0 (1.0-3.0)
During SUD periodd, n (%)
3 (30.0)
0 (0)
During 1st full cycled, n (%)
0 (0)
2 (11.8)
During 2nd full cycle or afterd, n %)
1 (10.0)
0 (0)
CRS recovered or resolvedd, n (%)
4 (100.0)
2 (100.0)
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; SUD, step-up dose.
aCRS was graded by ASTCT criteria.
bOne patient treated on an outpatient basis had CRS while hospitalized for bone pain.
cRelative to the most recent dose.
dPatients could have ≥1 event.

CLINICAL DATA - Monumental-2 study

MonumenTAL-2 (NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with MM.7-9

Study Design/Methods

  • Key eligibility criteria:
    • Cohort D: measurable MM, NDMM, ECOG PS of 0-1, and transplant ineligible or not intended for transplant.9
    • Cohort E: measurable MM; ≥2 prior LOTs, including a PI and an immunomodulatory drug; ECOG PS of 0-1; prior pomalidomide and prior TCR (CAR-T and BsAb) permitted; and no prior GPRC5D-targeted therapy.7

Cohort D

Nooka et al (2024)9 presented the incidence of CRS of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0–14.6) and the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).

Safety Results


MonumenTAL-2 Study (Cohort D): Summary of CRS Events9
TEAE, n (%)
TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO +
Lenalidomide
(n=8)
TALVEY 0.8 mg/kg Q4W +
DARZALEX FASPRO +
Lenalidomide
(n=26)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
CRS
7 (87.5)
0
20 (76.9)
0
Abbreviations: CRS, cytokine release syndrome; Q2W, every other week; Q4W, every 4 weeks; TEAE, treatment-emergent adverse event.
Clinical data cutoff date of September 23, 2024.

Cohort E

Quach et al (2025)7 presented the incidence of CRS from the TALVEY + pomalidomide cohort of the MonumenTAL-2 study at a longer median follow-up of 20.7 months (range, 1.2-38.7).

Safety Results

  • At a data cutoff of March 2025, CRS was evaluated in the TALVEY + pomalidomide cohort (N=35).
  • Any-grade CRS was reported in 74.3% of patients and grade 3/4 CRS in 2.9% of patients. CRS primarily occurred during step-up dosing and cycle 1; addition of pomalidomide at cycle 2 did not increase CRS events.

CLINICAL DATA - redirectt-1 STUDY - TALVEY + tecvayli COHORT

RedirecTT-1 (NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI in patients with RRMM, including those with EMD.10-13 

Study Design/Methods

  • Key eligibility criteria: relapsed or refractory or intolerant to established therapies including the last LOT; prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 mAb.13

Usmani et al (2025)10 presented the incidence of CRS from the RedirecTT-1 phase 2 study in patients with RRMM and EMD at a median follow-up of 16.8 months.

Safety Results

  • At a data cutoff date of July 18, 2025, CRS was evaluated in 90 patients.
  • Any-grade CRS events were reported in 77.8% of patients; grade 3/4 CRS events were not reported.

Kumar et al (2025)11,22 published the incidence of CRS from phase 2 of the RedirecTT-1 study at a median follow-up of 12.6 months (range, 0.5-19.5) in patients with RRMM and EMD.

Safety Results

  • At the data cutoff date of March 18, 2025, the incidence of CRS was evaluated in patients with RRMM and EMD (N=90).
  • CRS was graded per American Society for Transplantation and Cellular Therapy (ASTCT) criteria. AEs were reported up to 30 days after the patient received the last dose of study treatment or until the start of subsequent antimyeloma therapy, whichever occurred first.
  • Any-grade CRS was reported in 77.8% of patients (n=70), grade 1 in 58.9% of patients (n=53), grade 2 in 18.9% of patients (n=17), and grade 3/4 CRS was not reported.  
  • CRS events mostly occurred only during the step-up dosing phase and cycle 1.
  • Median time to onset was 2 days (range, 1-29) relative to the most recent dose based on 122 CRS events.
  • Median duration was 2 days (range, 1-8) among events with both start and end dates available, based on 121 CRS events.
  • More than one CRS event was reported in 41.1% of patients (n=37); grade of CRS worsened at any subsequent event in 6.7% of patients (n=6).
  • Among patients with CRS, 97% (n=68) received supportive measures (patients could receive ≥1 supportive therapy):
    • Acetaminophen: 56.7% of patients (n=51).
    • Tocilizumab: 56.7% of patients (n=51).
    • Other supportive measures: 37.8% of patients (n=34).
    • Corticosteroids: 18.9% of patients (n=17).
    • IV fluids: 17.8% of patients (n=16).
    • Oxygen: 4.4% of patients (n=4).
    • Vasopressor: 1.1% of patients (n=1).
  • At data cutoff, 99% of CRS events (121/122) had resolved.

Mateos et al (2025)12 presented the incidence of CRS from phase 1b of the RedirecTT-1 study across all dose levels (dose levels 1-5) at a median follow up of 38 months, in patients with RRMM, including those with EMD.

Safety Results

  • At a data cutoff date of July 2025, CRS was evaluated across all dose levels (N=94).
  • Any-grade CRs events were reported in 80.9% of patients; grade 3/4 CRS events were reported in 2.1% of patients.

Cohen et al (2025)13 published the incidence of CRS from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) across dose levels (dose levels 1-5) and 18.2 months in the recommended phase 2 regimen (RP2R; dose level 5) cohorts.

Safety Results

  • Details on the occurrence and management of CRS are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS.13,23 
  • CRS was graded per ASTCT criteria. AEs were reported up to 30 days after the patient received the last dose of study treatment.
  • Across all dose levels (N=94), CRS events were reported in 79% of patients (n=74), including 53.2% of patients (n=50) with grade 1, 23.4% of patients (n=22) with grade 2, and 2% of patients (n=2) with grade 3.13,23 
  • In the RP2R cohort (n=44), CRS events were reported in 75% of patients (n=33), including 52.3% of patients (n=23) with grade 1 and 22.7% of patients (n=10) with grade 2; no grade 3 CRS events were reported.13,23 
  • Most CRS events occurred during step-up dosing and cycle 1 day 1 doses.23

RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS13,23 
Parameter
All Dose Levels
(N=94)
RP2R
(n=44)
Cycle delays or dose modification, n (%)
14 (15)
-
Median time to onseta, days (range)
2 (1-733)
2 (1-4)
Median duration, days (range)
2 (1-8)
2 (1-5)
Patients who received supportive measuresb, n (%)
61 (65)
28 (63.6)
   Tocilizumab
24 (26)
10 (22.7)
   Intravenous fluids
11 (11.7)
8 (18.2)
   Corticosteroids
 3 (3.2)
1 (2.3)
   Oxygen
1 (1.1)
1 (2.3)
   Vasopressor
1 (1.1)
0 (0)
Recovery, %
98
-
   Recovery with sequelae
1
-
   Incomplete recovery
1
-
Abbreviations: CRS, cytokine release syndrome; RP2R, recommended phase 2 regimen.
Clinical data cutoff date of March 15, 2024. The median follow-up time was 20.3 months (range, 0.5-37.1) and 18.2 months for the all dose levels cohort and RP2R cohorts, respectively.
aRelative to the most recent dose.
bPatients could receive >1 supportive therapy. Other forms of supportive measures were received by 12 patients (RP2R) and 26 patients (across all dose levels).

CLINICAL DATA - TRIMM-2 STUDY - TALVEY + DARZALEX FASPRO COHORT

TRIMM-2 (NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating DARZALEX FASPRO regimens in combination with bispecific TCR antibodies in patients with RRMM.14-16

Study Design/Methods

  • Key eligibility criteria15:
    • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior LOTs (including a PI and an immunomodulatory drug).
    • Treatment with an anti-CD38 mAb (>90 days prior allowed) including anti-CD38 refractory patients.
    • Prior BsAb and CAR-T were allowed.

Chari et al (2025)15,24 published the incidence of CRS in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohorts at a median follow-up of 18.6 months (range, 1.2-39.1).

Safety Results

  • CRS was reported in 78% of patients (n=51); all events were grade 1/2 and occurred mostly during step-up and cycle 1 doses. All resolved. See Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO Cohort): CRS Events for additional details.
  • No grade 3/4 CRS events were reported.
  • Dose skips of TALVEY due to CRS was reported in 3% of patients (n=2).

TRIMM-2 Study (TALVEY + DARZALEX FASPRO Cohort): CRS Events24
Parameter
TALVEY 0.4 mg/kg QW + DARZALEX FASPRO
(n=14)
TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO
(n=51)
Patients with CRSa, n (%)
10 (71)
41 (80)
   Grade 1
8 (57)
29 (57)
   Grade 2
2 (14)
12 (24)
Median time to onsetb, days (range)
3 (1-4)
2 (1-4)
Median duration, days (range)
2 (1-10)
2 (1-9)
Received supportive measuresc, n (%)
9 (64)
38 (74.5)
   Tocilizumabd
7 (50)
21 (41)
   Paracetamol
6 (43)
35 (69)
   Oxygen
0 (0)
3 (6)
   Corticosteroids
0 (0)
3 (6)
   Othere
7 (50)
38 (74.5)
Outcome, n (%)
   Recovered or resolved
17 (100)
69 (96)
   Not recovered or resolved
0 (0)
2 (3)
Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; Q2W, every other week; QW, once a week.
aCRS graded according to the ASTCT criteria.
bRelative to most recent dose (day of most recent dose=day 1).
cA patient could receive >1 supportive therapy.
dTocilizumab was allowed for all CRS events.
eMost common (>4 patients in the combined cohort) includes sodium chloride, piperacillin/tazobactam, metamizole sodium, cefepime, ceftriaxone, meropenem, and metamizole magnesium.
Data cutoff date: November 17, 2023.

Bahlis et al (2024)14 presented the incidence of CRS in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts at a median follow-up of 15.8 months (range, 3.2-37.9) and 17.5 months (range, 0.2-37.7), respectively.

Safety Results


TRIMM-2 Study (TALVEY + DARZALEX FASPRO + Pomalidomide Cohort): CRS Events14
Parameter
TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + Pomalidomide
(n=18)
TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + Pomalidomide
(n=59)
Patients with CRSa,n (%)
10 (55.6)
47 (79.7)
   Grade 1
7 (38.9)
32 (54.2)
   Grade 2
3 (16.7)
15 (25.4)
Median time to onset (range)b,days
3 (1-5)
2 (1-7)
Median duration (range), days
2 (1-6)
2 (1-7)
Received supportive measuresc,n (%)
10 (55.6)
42 (71.2)
   Tocilizumab
7 (38.9)
34 (57.6)
   Acetaminophen
7 (38.9)
27 (45.8)
   Corticosteroids
0 (0)
8 (13.6)
   Oxygen
0 (0)
2 (3.4)
   Other
8 (44.4)
30 (50.8)
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; Q2W, every other week; QW, weekly.
Clinical data cutoff date of July 29, 2024.
aCRS were graded per ASTCT criteria.
bRelative to the most recent dose (day of most recent dose=day 1).
cA patient could receive >1 supportive therapy.

CLINICAL DATA - TRIMM-3 Study - TALVEY + PD-1 inhibitor COHORT

TRIMM-3 (NCT05338775) is a phase 1b, nonrandomized, open-label study evaluating the dosing, safety, and tolerability of TALVEY in combination with cetrelimab.17,18

Study Design/Methods

  • Key eligibility criteria17:
    • MM per IMWG criteria
    • RRMM who may not be eligible for or expected to benefit from available therapies
    • ECOG PS 0 or 1

Perrot et al (2025)17 presented the incidence of CRS of the TALVEY + cetrelimab cohort at a median follow-up of 11.5 months (range, 1.5-32.3).

Safety Results

  • CRS primarily occurred during step-up dosing and cycle 1 (prior to the cetrelimab administration) without any treatment discontinuation; all events resolved. No grade ≥3 CRS events were reported. A summary of CRS events is presented in Table: TRIMM-3 Study: CRS Events.

TRIMM-3 Study: CRS Events17 
Parameter
All Patients
(N=44)
Patients with CRSa, n (%)
27 (61.4)
   Grade 1
20 (45.5)
   Grade 2
7 (15.9)
Time to onset (days)b, median (range)
2 (1-11)
Duration (days), median (range)
2 (1-7)
Received supportive measuresc, n (%)
24 (54.5)
   Tocilizumab
15 (34.1)
   Corticosteroids
1 (2.3)
   Other
19 (43.2)
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome.
Clinical data cutoff date of April 2, 2025.
aCRS and ICANS were graded per ASTCT criteria.
bRelative to the most recent dose (day of the most recent dose=day 1).
cA patient could receive >1 supportive therapy.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 06 February 2026.

 

References

Show
1 Chari A, Touzeau C, Schinke C, et al. Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study. Lancet Haematol. 2025;12(4):e269-e281.  
2 van de Donk NWCJ, Chari A, Martin T, et al. Characterization and management of cytokine release syndrome from the MonumenTAL-1 study of talquetamab in patients with relapsed/refractory multiple myeloma. Cancer Med. 2025;14(19):e71276.  
3 Rasche L, Schinke C, Touzeau C, et al. Efficacy and safety from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: analyses at an extended median follow-up. Poster presented at: The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2025; Chicago, IL/Virtual.  
4 Schinke C, Vij R, Jagannath S, et al. Prophylactic tocilizumab to mitigate cytokine release syndrome in patients receiving talquetamab for relapsed/refractory multiple myeloma: results from the phase 1/2 MonumenTAL-1 study. Poster presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
5 Morillo D, Chamorro CM, Mateos MV, et al. Cytokine release syndrome in patients receiving alternative step-up doses of talquetamab for relapsed/refractory multiple myeloma: results from the phase 1/2 MonumenTAL-1 study. Poster presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
6 Dytfeld D, Vij R, Jagannath S, et al. Prophylactic tocilizumab to mitigate cytokine release syndrome and outpatient dosing of talquetamab in relapsed/refractory multiple myeloma: updated phase 1/2 MonumenTAL-1 results. Poster presented at: The European Hematology Association (EHA) Hybrid Congress; June 12-15, 2025; Milan, Italy.  
7 Quach H, Perrot A, Matous JV, et al. Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with pomalidomide in patients with relapsed/refractory multiple myeloma: updated safety and efficacy results from the phase 1b MonumenTAL-2 study. Poster presented at: The 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, FL.  
8 Janssen Research & Development, LLC. A multi-arm phase 1b study of talquetamab with other anticancer therapies in participants with multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 February 6]. Available from: https://clinicaltrials.gov/ct2/show/NCT05050097 NLM Identifier NCT05050097.  
9 Nooka AK, Cochrane T, D’Souza A, et al. Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with daratumumab and lenalidomide in patients with newly diagnosed multiple myeloma: safety and efficacy results from the phase 1b MonumenTAL-2 study. Poster presented at: The 66th American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024; San Diego, CA.  
10 Usmani SZ, Kumar S, Mateos MV, et al. Efficacy and safety of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: updated phase 2 results from the RedirecTT-1 study with extended follow-up. Oral Presentation presented at: the 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, FL.  
11 Kumar S, Mateos MV, Ye JC, et al. Dual targeting of extramedullary myeloma with Talquetamab and Teclistamab. N Engl J Med. 2026;394(1):51-61.  
12 Mateos MV, Magen H, Gatt M, et al. Safety and efficacy of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma from phase 1b of RedirecTT-1: results with an extended median follow-up of 3 years. Oral presentation presented at: the 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, FL.  
13 Cohen YC, Magen H, Gatt M, et al. Talquetamab plus teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2025;392(2):138-149.  
14 Bahlis N, van de Donk NWCJ, Reece D, et al. Talquetamab + daratumumab + pomalidomide in patients with relapsed/refractory multiple myeloma: results from the phase 1b TRIMM2 study. Oral Presentation presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
15 Chari A, van de Donk NWCJ, Dholaria B, et al. Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood. 2025;146(24):2902-2913.  
16 Janssen Research & Development, LLC. A phase 1b study of subcutaneous daratumumab regimens in combination with bispecific T cell redirection antibodies for the treatment of subjects with multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 February 6]. Available from: https://clinicaltrials.gov/ct2/show/NCT04108195 NLM Identifier: NCT04108195.  
17 Perrot A, Touzeau C, Rodríguez-Otero P, et al. Talquetamab + cetrelimab in patients with relapsed/refractory multiple myeloma: initial safety and efficacy results from the phase 1b TRIMM-3 study. Oral Presentation presented at: the European Hematology Association (EHA) Annual Meeting; June 12-15, 2025; Milan, Italy.  
18 Janssen Research & Development, LLC. A phase 1b study of bispecific T cell redirection antibodies in combination with checkpoint inhibition for the treatment of participants with relapsed or refractory multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 February 6]. Available from: https://clinicaltrials.gov/study/NCT05338775 NLM Identifier: NCT05338775.  
19 Jakubowiak AJ, Anguille S, Karlin L, et al. Updated results of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma with prior exposure to T-cell redirecting therapies: results of the phase 1/2 MonumenTAL-1 study. Poster presented at: The 65th American Society of Hematology (ASH) Annual Meeting; December 9-12, 2023; San Diego, CA/Virtual.  
20 Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab, a GPRC5DxCD3 bispecific antibody, for relapsed/refractory multiple myeloma. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL/Virtual.  
21 van de Donk NWCJ, Chari A, Martin T, et al. Supplement to: Characterization and management of cytokine release syndrome from the MonumenTAL-1 study of talquetamab in patients with relapsed/refractory multiple myeloma. Cancer Med. 2025;14(19):e71276.  
22 Kumar S, Mateos MV, Ye JC, et al. Protocol to: Dual targeting of extramedullary myeloma with Talquetamab and Teclistamab. N Engl J Med. 2026;394(1):51-61.  
23 Cohen YC, Magen H, Gatt M, et al. Talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma: updated phase 1b results from RedirecTT-1 with >1 year of follow-up. Oral Presentation presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
24 Chari A, van de Donk NWCJ, Dholaria B, et al. Supplement to: Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood. 2025;146(24):2902-2913.