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TALVEY®

(talquetamab-tgvs)

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TALVEY® (talquetamab-tgvs)

Medical Information

MonumenTAL-1

TALVEY® (talquetamab-tgvs) received approval from the FDA in August 2023 for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1,2

MonumenTAL-1 (NCT03399799, NCT04634552) was a single-arm, open-label, multicenter phase 1/2 study evaluating the efficacy of TALVEY® monotherapy in patients with relapsed or refractory multiple myeloma.1

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

See Full Prescribing Information for complete boxed warning

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY®. Initiate TALVEY® treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur with TALVEY®. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment and treat promptly. Withhold or permanently discontinue TALVEY® based on severity.

Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).

Key eligibility criteria1

Inclusion criteria:

  • Patients with relapsed or refractory multiple myeloma
  • Previously received at least 3 prior systemic therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody

Exclusion criteria:

  • Experienced T-cell redirection therapy within 3 months
  • Prior Grade 3 or higher cytokine release syndrome related to any T-cell redirection therapy
  • Experienced autologous stem cell transplantation within the past 6 months
  • ECOG performance score ≥3
  • Stroke or seizure within the past 6 months
  • CNS involvement or clinical signs of meningeal involvement of multiple myeloma
  • Plasma cell leukemia
  • Active or documented history of autoimmune disease (exception of vitiligo, resolved childhood atopic dermatitis, resolved Grave’s Disease that is euthyroid based on clinical and laboratory testing)

Design: single-arm, open-label, multicenter study, MMY1001 (MonumenTAL-1; NCT03399799, NCT04634552)1

Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of TALVEY® followed by TALVEY® 0.4 mg/kg subcutaneously weekly thereafter.

Patients treated with the biweekly (every 2 weeks) dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) of TALVEY® followed by TALVEY® 0.8 mg/kg subcutaneously biweekly, thereafter.

Patients on both dosing schedules were treated until disease progression or unacceptable toxicity.1

Primary endpoint3
  • Overall Response Rate (ORR), defined as the proportion of participants who have a partial response (PR) or better according to the IMWG criteria
Key secondary endpoints3
  • Duration of Response (DOR)
  • Progression-free survival (PFS)
  • Overall survival
  • Safety
  • Pharmacokinetics
  • Patient-reported outcomes
  • Minimal residual disease

Baseline patient characteristics and treatment history in patients with multiple myeloma without prior T-cell redirection therapy who received TALVEY® in MonumenTAL-11:

Baseline patient characteristics Patients without prior T-cell
redirection therapy (n=187)
Age
Median age, years (range) 67 (38-86)
Sex
Male, % 57
Race, %
White 90
Black or African American 5
Asian 3
Hispanic 8
Treatment history
Prior lines of therapy, median (range) 5 (4-13)
Prior autologous stem cell transplantation, % 78
Refractory to last therapy, % 94
Refractory to proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody, % 73
ISS stage at study entry, %
Stage I 44
Stage II 34
Stage III 22
Other characteristics, %
High-risk cytogenetics* 29†
Extramedullary plasmacytomas 22

*Presence of t(4;14), t(14;16), and/or del(17p).
†Baseline cytogenetic data were not available in 11% of patients.

In patients without prior T-cell redirection therapy and receiving TALVEY® 0.4 mg/kg weekly:

  • The median duration of follow-up from first response among responders was 13.8 (range: 0.8 to 15.4) months
  • The median DOR was 9.5 (95% CI: 6.5-NE) months
  • The median time to response was 1.2 (range: 0.2 to 10.9) months

In patients without prior T-cell redirection therapy and receiving TALVEY® 0.8 mg/kg biweekly (every 2 weeks):

  • The median duration of follow-up from first response among responders was 5.9 (range: 0 to 9.5) months; an estimated 85% of responders maintained response for at least 9 months
  • The median DOR was NE
  • The median time to first response was 1.3 (range: 0.2 to 9.2) months
  • Thirty-two patients were exposed to prior T-cell redirection therapy and had received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody received TALVEY® at the 0.4 mg/kg weekly dose.
  • The ORR per IRC was 72% (95% CI: 53-86%).
  • With a median duration of follow-up of 10.4 months, an estimated 59% of responders maintained response for at least 9 months.

Exposed to T-cell redirection therapy‡

Patient characteristics SC QW (N=32)
Prior lines of therapy, median (range) 6 (4-15)
Triple-class exposed (proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody) 100%
Prior CAR-T therapy 81%
Prior bispecific antibody therapy 25%
Prior BCMA-directed therapy 94%

‡T-cell redirection therapy refers to both CAR-T and bispecific antibody therapy.

Efficacy from MonumenTAL-1 is reported at an extended mFU of >28-30 months4

You are now viewing a subsequent follow-up analysis of the MonumenTAL-1 trial. This information is not included in the current Full Prescribing Information. These longer-term follow-up data reflect the patients naïve to TCR therapy* receiving TALVEY® Q2W; any increase in n-value is due to this longer-term follow-up and additional patients.

Time to response

mTTR:
1.3 months

(range: 0.2 to 3.6 months)

Duration of response

mDOR:
17.9 months

(95% CI, 12.5 to 26.0 months)

Time to CR or better

mTTCR:
5.8 months

(range: 1.2 to 13.1 months)

*T-cell redirection therapy refers to both CAR-T and bispecific antibody therapy.

†ORR: sCR+CR+PR+VGPR. ORR was assessed by an IRC using IMWG criteria. Due to rounding, individual response rates may not sum to the ORR.

You are now viewing a subsequent follow-up analysis of the MonumenTAL-1 trial. This information is not included in the current Full Prescribing Information. These longer-term follow-up data reflect the patients naïve to TCR therapy* receiving TALVEY® QW.

Time to response

mTTR:
1.2 months

(range: 0.2 to 10.9 months)

Duration of response

mDOR:
10.2 months

(95% CI, 6.6 to 15.7 months)

Time to CR or better

mTTCR:
2.1 months

(range: 1.1 to 12.2 months)

*T-cell redirection therapy refers to both CAR-T and bispecific antibody therapy.

†ORR: sCR+CR+PR+VGPR. ORR was assessed by an IRC using IMWG criteria. Due to rounding, individual response rates may not sum to the ORR.

You are now viewing a subsequent follow-up analysis of the MonumenTAL-1 trial. This information is not included in the current Full Prescribing Information. These longer-term follow-up data reflect the patients exposed to TCR therapy* receiving TALVEY® QW; any increase in n-value is due to this longer-term follow-up and additional patients.

Time to response

mTTR:
1.2 months

(range: 0.2 to 7.5 months)

Duration of response

mDOR:
19.2 months

(95% CI, 6.7 months to NE)

Time to CR or better

mTTCR:
2.6 months

(range: 1.0 to 12.9 months)

ORR in patients exposed to BCMA CAR-T and BCMA bispecific antibody therapy:

Prior BCMA CAR-T exposure

ORR‡
73.3%

N=45§
(95% CI, 58.1%-85.4%)

Prior BCMA bispecific antibody exposure

ORR‡
76.5%

N=17§
(95% CI, 50.1%-93.2%)

*T-cell redirection therapy refers to both CAR-T and bispecific antibody therapy.

†ORR: sCR+CR+PR+VGPR. ORR was assessed by an IRC using IMWG criteria. Due to rounding, individual response rates may not sum to the ORR.

‡Efficacy results reflect patients who have received ≥4 prior lines of therapy.

§N values increased from primary analysis due to continued patient enrollment.

Contraindications1:

  • None

Warnings and precautions1:

Please see the Full Prescribing Information for more details.

Cytokine release syndrome

TALVEY® can cause cytokine release syndrome, including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received TALVEY® at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (29%) or step-up dose 2 (44%) at the recommended dosages. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).

Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY® in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY® dose.

Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity, and consider further management per current practice guidelines. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity including ICANS

TALVEY® can cause serious, life-threatening neurologic toxicity or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).

In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction, including ataxia/cerebellar ataxia (10%). ICANS was reported in 9% of 265 patients where ICANS was collected and who received the recommended dosages. Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.

Monitor patients for signs and symptoms of neurologic toxicity during treatment and treat promptly. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity. Withhold or permanently discontinue TALVEY® based on severity and consider further management per current practice guidelines [see Dosage and Administration (2.5)].

Due to the potential for neurologic toxicity, patients receiving TALVEY® are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule, and in the event of new onset of any neurological symptoms, until symptoms resolve.

TECVAYLI® AND TALVEY® REMS

TALVEY® is available only through a restricted program under a REMS, called the TECVAYLI® and TALVEY® REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Further information about the TECVAYLI® and TALVEY® REMS program is available at

www.TEC-TALREMS.com or by telephone at 1-855-810-8064.

Oral toxicity and weight loss

TALVEY® can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis.

In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients.

TALVEY® can cause weight loss. In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss.

Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice, including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY® or permanently discontinue based on severity.

Infections

TALVEY® can cause infections, including life-threatening or fatal infections.

Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis, and COVID-19 (2.7%).

Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY® and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanent discontinuation of TALVEY® as recommended based on severity.

Cytopenias

TALVEY® can cause cytopenias, including neutropenia and thrombocytopenia.

In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY®. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY® as recommended based on severity.

Skin toxicity

TALVEY® can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash.

In the clinical trial, skin reactions occurred in 62% of patients, with Grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to Grade 1 or less was 33 days.

Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold TALVEY® as recommended based on severity.

Hepatotoxicity

TALVEY® can cause hepatotoxicity. Elevated ALT occurred in 33% of patients, with Grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with Grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY® or consider permanent discontinuation of TALVEY® based on severity [see Dosage and Administration (2.5)].

Embryo-fetal toxicity

Based on its mechanism of action, TALVEY® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY® and for 3 months after the last dose.

Adverse reactions

The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.

The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

Please read Full prescribing information, including Boxed WARNING, for TALVEY®.

cp-394174v6

Characterization and management of CRS in MonumenTAL-15

  • As of January 17, 2023, 288 patients with no prior TCR received talquetamab 0.4mg/kg QW (n=143; median follow-up, 18.8 months) or 0.8mg/kg Q2W (n=145; median follow-up, 12.7 months)
  • Fifty-one patients in the prior TCR cohort (median follow-up, 14.8 months) received either QW (n=43) or Q2W (n=8)
    • Of the 51 patients, 36 received a CAR-T therapy and 18 received a bispecific antibody
Median (range) time, days*
QW Cohort
Step-up dose 1 to 2 2.8 (1-7)
Step-up dose 2 to C1D1 3.0 (1-8)
Q2W Cohort
Step-up dose 1 to 2 2.0 (1-8)
Step-up dose 2 to 3 2.9 (1-7)
Step-up dose 3 to C1D1 2.9 (1-12)

*Excluding patients who received additional step-up doses (ie, repeat step-up dosing) before the first full dose in C1.

  • CRS incidence was similar across cohorts (74.5%–79.0%)
  • Common symptoms were pyrexia (73.8%–79.0%), hypotension (13.8%–21.6%), and chills (9.1%–17.6%)
  • CRS events were primarily low-grade, with few grade 3 (0.7%–2.1%) and no grade 4/5 events
Parameter QW
(n = 143) 		Q2W
(n = 145) 		Prior TCR
(n = 51)
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 CRS*, n (%) 24 (16.8) 15 (10.3) 6 (11.8)
CRS leading to discontinuation, n (%) 0 1 (0.7) 0

*Defined as inpatient hospitalization or prolongation of existing hospitalization (for >24h)

  • The median time to onset and duration of CRS were captured consistently only in phase 2 for the QW, Q2W, and prior TCR cohorts (n=141, 140, and 36, respectively, for time to onset, and n=139, 138, and 36, respectively, for duration of CRS)
  • While the range of CRS onset was 0.1–333 hours across cohorts, 89%–92% of events occurred within 48h of the most recent talquetamab dose
  • Median duration of CRS events was similar across cohorts (15–20 [range 0–622] hours)
  • At data cutoff, all CRS events had resolved, except in one patient in the QW cohort
  • Most first CRS events occurred following step-up dose 1 (24%– 34%), 2 (27%–37%), 3 (15%; Q2W schedule only), and first full dose (3%–22%)
  • In the Q2W cohort, three patients had a first CRS event at C1D1, all grade 2
  • There were no grade 2 events beyond C1D1, and no grade 3 events beyond C1D8
Parameter QW
(n = 143) 		Q2W
(n = 145) 		Prior TCR
(n = 51)
Time to onset (h),*† median (range) 25.9 (1.3-165.0) 28.0 (0.1-333.4) 26.3 (4.9-92.2)
Duration (h),‡ median (range) 14.5 (0.5-221.6) 18.0 (0.0-621.8) 20.4 (0.9-71.5)
Patients with CRS up to first full dose, n (%)
First step-up dose 48 (33.6) 38 (26.2) 12 (23.5)
Second step-up dose 70 (49.0) 59 (40.7) 21 (41.2)
Third step-up dose N/A 50 (34.5) 1 (2.0)
First 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 step-up dosing,‡ n (%) 0 3 (10.7) 1 (20.0)
Patients with first CRS up to first full dose, n (%)
First step-up dose 48 (33.6) 38 (26.2) 12 (23.5)
Second step-up dose 53 (37.1) 39 (26.9) 16 (31.4)
Third step-up dose N/A 22 (15.2) 0
First full dose 8 (5.6) 5 (3.4) 11 (21.6)
Patients with first CRS during cycle ≥2, n (%) 0 3 (2.1) 0

*Relative to the most recent dose. †Calculated 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, respectively, for duration of CRS. ‡Calculated based on patients who received repeat step-up dosing (n=8, 28 and 5, respectively).

  • CRS occurred concurrently with infections in three (2.7%), nine (8.3%), and 0 patients in the QW, Q2W, and prior TCR cohorts, respectively
  • CRS occurred concurrently with neutropenia in nine (8.0%), two (1.9%), and three (7.7%) patients, respectively
  • Most recurrent CRS events occurred during step-up dosing (11.9%, 15.0%, and 9.8%) and C1D1 (21.0%, 10.5%, and 11.8%), and fewer occurred beyond C1D1 (11.2%, 5.5%, and 5.9%)
  • Median onset of recurrent CRS was 26–29 hours from the last dose of talquetamab
  • In general, most patients who had a CRS event after C1D8 had experienced a previous CRS event with ≥1 step-up or C1D1 dose; of these, most were grade 1, except one grade 3 event after C1D8, which occurred concurrently with bacteremia
Parameter QW
(n = 143) 		Q2W
(n = 145) 		Prior TCR
(n = 51)
Repeat step-up for first CRS 0 0 0
Average inpatient stay (days), n (range) 7.5 (2-36) 9.0 (2-20) 8.0 (2-19)
Patients who received supportive measures,* n (%) 106 (74.1) 103 (71.0) 39 (76.5)
Tocilizumab† 50 (35.0) 55 (37.9) 26 (51.0)
Corticosteroids 5 (3.5) 5 (3.4) 8 (15.7)
Oxygen‡ 8 (5.6) 10 (6.9) 3 (5.9)
Nasal canula 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 6 (4.2) 6 (4.1) 3 (5.9)

*Patients could receive more than one supportive therapy. †Tocilizumab was allowed for all CRS events; the protocol prohibited prophylactic tocilizumab use. ‡Primarily low flow.

Talquetamab can cause infections, including life-threatening or fatal infections. Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis, and COVID-19 (2.7%).

Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY® and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanent discontinuation of TALVEY® as recommended based on severity.

The most common infections were respiratory infections including COVID-19 and upper respiratory infections.

Number of infections in each cohort according to grade

Data cutoff: January 17, 2023. Median follow-up: 18.8 (QW), 12.7 (Q2W), and 14.8 (prior TCR) months.

Infection rates over time across cohorts

  • At baseline, median CD19+ B-cell counts were 5.3, 10.1, and 22.8 (x106/L) in the QW, Q2W, and prior TCR cohorts, respectively
  • CD19+ B-cell frequencies remained stable throughout early treatment cycles, with an increasing trend noted at cycle 7
  • After initiation of treatment, hypogammaglobulinemia (IgG values <400 mg/dL) was reported in 57.3%, 60.7%, and 66.7% of patients in the QW, Q2W, and prior TCR cohorts, respectively
  • Treatment-emergent HGG occurred in 23.1%, 28.3%, and 19.6% of patients, respectively
  • Polyclonal IgG levels initially decreased from baseline to cycle 3 (3 months) in the combined cohorts, mostly due to patients in the prior TCR cohort, as levels in the QW and the Q2W cohorts remained largely stable and below the LLN (7.0 g/L) during this period

CD19+ B-cell levels in all cohorts

Percentage of patients with hypogammaglobulinemia (IgG values <400 mg/dL) after treatment initiation

Percentage of patients that started intravenous immunoglobulin (IVIG) while on treatment

  • Serious adverse reactions occurred in 47% of patients who received TALVEY®. Serious adverse reactions in ≥2% of patients included1:
Pneumonia

CRS (13%)

COVID-19

Bacterial infection
(8%) including sepsis

Diarrhea

Pyrexia (4.7%)

Thromboembolism

ICANS (3.8%)

Pneumonia

COVID-19 (2.7%)

COVID-19

Neutropenia (2.1%)

Diarrhea

Upper respiratory
tract infection (2.1%)

Pneumonia

CRS
(13%)

COVID-19

Bacterial infection
(8%) including
sepsis

Diarrhea

Pyrexia
(4.7%)

Thromboembolism

ICANS
(3.8%)

Pneumonia

COVID-19
(2.7%)

COVID-19

Neutropenia
(2.1%)

Diarrhea

Upper respiratory
tract infection (2.1%)

  • Duration of exposure for Q2W was 3.7 months (range: 0.0 to 17.9) (N=153) and for QW was 5.9 months (range: 0.0 to 25.3) (N=186).
  • Clinically relevant adverse reactions reported in <10% of patients who received TALVEY® included ICANS and viral infection.
  • Fatal adverse reactions occurred in 3.2% of patients who received TALVEY®, including COVID-19 (0.6%), dyspnea (0.6%), general physical health deterioration (0.6%), bacterial infection (0.3%) including sepsis, basilar artery occlusion (0.3%), fungal infection (0.3%), infection (0.3%), and pulmonary embolism (0.3%).
  • Permanent treatment discontinuation of TALVEY® due to an adverse reaction occurred in 9% of patients. 
  • Adverse reactions which resulted in permanent discontinuation of TALVEY® in >1% of patients included ICANS.
  • Dosage interruptions of TALVEY® due to an adverse reaction occurred in 56% of patients.
  • Adverse reactions which required dosage interruption in >5% of patients included pyrexia (15%), CRS (12%), upper respiratory tract infection (9%), COVID-19 (9%), bacterial infection (7%) including sepsis, neutropenia (6%), and rash (6%).

The most common adverse reactions (≥20%) included1:

  • Pyrexia
  • CRS
  • Dysgeusia
  • Nail disorder
  • Musculoskeletal pain
  • Skin disorder
  • Rash
  • Fatigue
  • Weight decreased
  • Dry mouth
  • Xerosis
  • Dysphagia
  • Upper respiratory tract infection
  • Diarrhea
  • Hypotension
  • Headache

The most common Grade 3 or 4 laboratory abnormalities (≥30%) were1:

  • Lymphocyte count decreased
  • Hemoglobin decreased
  • Neutrophil count decreased
  • White blood cell decreased

System organ class
adverse reaction		 TALVEY®
N = 339
Any grade
(%)		 Grade 3 or 4
(%)
General disorders and administration site conditions General disorders and administration site conditions
Pyrexiaa 83 4.7b
Fatiguea 37 3.5b
Chills 19 0
Paina 18 1.8b
Edemaa 14 0
Injection site reactiona 13 0
Immune system disorders
Cytokine release syndrome 76 1.5b
Gastrointestinal disorders
Dysgeusiac,d 70 0
Dry mouthc 34 0
Dysphagia 23 0.9b
Diarrhea 21 0.9b
Stomatitise 18 1.2b
Nausea 18 0
Constipation 16 0
Oral disorderf 12 0
Skin and subcutaneous tissue disorders
Nail disorderg 50 0
Skin disorderh 41 0.3b
Rashi 38 3.5b
Xerosisj 30 0
Pruritus 19 0.3b
Musculoskeletal and connective tissue disorders
Musculoskeletal paina 43 3.2b
Investigations
Weight decreased 35 1.5b
Infections and infestations
Upper respiratory tract infectiona 22 2.7b
Bacterial infection including sepsisk,l 19 9
COVID-19a,l 11 2.7
Fungal infectionl,m 10 0.6
Vascular disorders
Hypotensiona 21 2.9
Nervous system disorders
Headachea 21 0.6b
Encephalopathyn 15 1.8b
Sensory neuropathyo 14 0
Motor dysfunctionp 10 0.6b
Metabolism and nutrition disorders
Decreased appetite 19 1.2b
Respiratory, thoracic and mediastinal disorders
Cougha 17 0
Dyspneaa,l 11 1.8
Hypoxiaa 10 1.5b
Cardiac disorders
Tachycardiaa 11 0.6b

Adverse reactions were graded based on CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria.
aIncludes other related terms. bOnly grade 3 adverse reactions occurred. cPer CTCAE v4.03, maximum toxicity grade for dysgeusia is 2 and maximum toxicity grade for dry mouth is 3. dDysgeusia: ageusia, dysgeusia, hypogeusia and taste disorder. eStomatitis: cheilitis, glossitis, glossodynia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, tongue discomfort, tongue erythema, tongue edema and tongue ulceration. fOral disorder: oral disorder, oral dysesthesia, oral mucosal exfoliation, oral toxicity and oropharyngeal pain. gNail disorder: koilonychia, nail bed disorder, nail cuticle fissure, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail pitting, nail ridging, nail toxicity, onychoclasis, onycholysis and onychomadesis. hSkin disorder: palmar-plantar erythrodysesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation and skin fissures. iRash: dermatitis, dermatitis acneiform, dermatitis contact, dermatitis exfoliative, dermatitis exfoliative generalized, erythema, exfoliative rash, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular and stasis dermatitis. jXerosis: dry eye, dry skin and xerosis. kBacterial infection including sepsis: bacteremia, bacterial prostatitis, carbuncle, cellulitis, citrobacter infection, clostridium difficile colitis, clostridium difficile infection, cystitis escherichia, cystitis klebsiella, diverticulitis, enterobacter bacteremia, escherichia pyelonephritis, escherichia sepsis, folliculitis, gastroenteritis escherichia coli, helicobacter gastritis, human ehrlichiosis, klebsiella bacteremia, klebsiella sepsis, moraxella infection, otitis media acute, pitted keratolysis, pneumococcal sepsis, pneumonia, pneumonia streptococcal, pseudomonal bacteremia, pyuria, renal abscess, salmonella sepsis, sepsis, septic shock, skin infection, staphylococcal bacteremia, staphylococcal infection, staphylococcal sepsis, streptococcal bacteremia, tooth abscess, tooth infection, urinary tract infection enterococcal, and urinary tract infection pseudomonal. lIncludes fatal outcome(s): COVID-19 (N=2), dyspnea (N=2), bacterial infection including sepsis (N=1), fungal infection (N=1). mFungal infection: body tinea, candida infection, ear infection fungal, esophageal candidiasis, fungal infection, fungal sepsis, fungal skin infection, genital candidiasis, onychomycosis, oral candidiasis, oral fungal infection, oropharyngeal candidiasis, tinea pedis, vulvovaginal candidiasis, and vulvovaginal mycotic infection. nEncephalopathy: agitation, altered state of consciousness, amnesia, aphasia, bradyphrenia, confusional state, delirium, depressed level of consciousness, disorientation, encephalopathy, hallucination, lethargy, memory impairment, mood altered, restlessness, sleep disorder and somnolence. oSensory neuropathy: dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, immune-mediated neuropathy, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sciatica and vestibular neuronitis. pMotor dysfunction: dysarthria, dysgraphia, dysmetria, dysphonia, gait disturbance, muscle atrophy, muscle spasms, muscular weakness and tremor.

Laboratory abnormality TALVEY®a
Any grade
(%)		 Grade 3 or 4
(%)
Hematology
Lymphocyte count decreased 90 80
White blood cell decreased 73 35
Hemoglobin decreased 67 30
Neutrophil count decreased 64 35
Platelet count decreased 62 22
Chemistry
Albumin decreased 66 2.1
Alkaline phosphatase increased 49 1.5
Phosphate decreased 44 13
Gamma-glutamyl transferase increased 38 7
Alanine aminotransferase increased 33 2.7
Potassium decreased 31 4.4
Sodium decreased 31 6
Aspartate aminotransferase increased 31 3.3

aThe denominator used to calculate the rate varied from 326 to 338 based on the number of patients with a baseline value and at least one post-treatment value. Laboratory toxicity grades are derived based on the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 4.03.

You are now viewing a subsequent follow-up analysis of the MonumenTAL-1 trial. This information is not included in the current Full Prescribing Information.

System organ class
adverse reaction		 TALVEY®
N = 375
Any grade
(%)		 Grade 3 or 4
(%)
General disorders and administration site conditions
Pyrexiaa 83.2 4.5b
Fatiguea 43.7 3.5b
Paina 24.3 2.4b
Chills 20.3 0.3b
Immune system disorders
Cytokine release syndrome 76.3 1.3b
Gastrointestinal disorders
Dry mouth 35.2 0
Diarrhea 26.1 1.3b
Dysphagia 23.7 0.8b
Nausea 20.5 0
Stomatitisc 20.8 1.1b
Constipation 20 0
Skin and subcutaneous tissue disorders
Nail disorderd 57.3 0
Skin disordere 43.7 0
Rashf 39.5 3.2b
Xerosisg 35.3 0
Pruritus 24.3 0.3b
Musculoskeletal and connective tissue disorders
Musculoskeletal paina 52.8 3.5b
Investigations
Weight decreased 40.5 3.5b
Infections and infestations
Upper respiratory tract infectiona 35.7 2.1b
COVID-19a,h 20.8 3.7
Vascular disorders
Hypotensioni 22.4 3.2
Nervous system disorders
Dysgeusiaj 72.8 0
Headachea 21.9 0.5b
Metabolism and nutrition disorders
Decreased appetite 24.8 1.3b
Respiratory, thoracic and mediastinal disorders
Cougha 24.5 0

Note: CRS was originally graded by Lee criteria (Lee et al 2014) in phase 1 and by ASTCT consensus grading system (Lee et al 2019) in phase 2, with conversion of grade in phase 1 to ASTCT based on data in eCRF. Toxicity grade by ASTCT is presented in this table, for both phase 1 and phase 2.
Note: Adverse events are reported until 100 days (phase 1) or 30 days (phase 2) after the last dose of talquetamab or until the start of subsequent anticancer therapy, if earlier.
Note: The output includes the diagnosis of CRS; the symptoms of CRS are included.
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event. Adverse events are coded using MedDRA Version 24.1.
*Median follow-up for MonumenTAL-1 cohorts: TCR-naïve Q2W is over 30 months; TCR-exposed is over 28 months; TCR-naïve QW is over 37 months.
aIncludes other related terms.
bOnly Grade 3 adverse reactions occurred.
cStomatitis includes: cheilitis, glossitis, glossodynia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, tongue discomfort, tongue erythema, tongue edema, and tongue ulceration.
dNail disorder includes: koilonychia, nail bed disorder, nail cuticle fissure, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail pitting, nail ridging, nail toxicity, onychoclasis, onycholysis, and onychomadesis.
eSkin disorder includes: palmar-plantar erythrodysesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation, and skin fissures.
fRash includes: dermatitis, dermatitis acneiform, dermatitis contact, dermatitis exfoliative, dermatitis exfoliative generalized, erythema, exfoliative rash, rash, rash erythematous, rash macular, rash maculopapular, rash popular, rash pruritic, rash pustular, rash vesicular, and stasis dermatitis.
gXerosis includes: dry eyes, dry skin, and xerosis.
hContains fatal outcome(s).
iHypotension includes: hypotension and orthostatic hypotension.
jDysgeusia includes: ageusia, dysgeusia, hypogeusia, and taste disorder.

7.5% of patients discontinued TALVEY® due to an adverse reaction4

Updated discontinuation rate reflects longer-term follow-up* data of MonumenTAL-1 cohorts with a total N value of 375.3

Adverse reaction Patients in the MonumenTAL-1 trial Longer-term follow-up population (N = 375)
Total occurrence,
n (%) 		Leading to dose
reduction, n (%) 		Leading to
discontinuation,
n (%)
Nervous system disorders
Taste-relateda 273 (72.8) 21 (5.6) 3 (0.8)
Skin and subcutaneous tissue disorders
Nail disorderb 215 (57.3) 3 (0.8) 0
Skin disorderc 164 (43.7)d 5 (1.3) 2 (0.5)
Rashe 148 (39.5)f 1 (0.3) 1 (0.3)
Xerosisg 133 (35.5) 1 (0.3) 1 (0.3)
Pruritus 91 (24.3)h 2 (0.5) 0
Investigations
Weight decreased 152 (40.5)i 13 (3.5) 4 (1.1)

Note: Dose reduction could mean increasing the interval between doses and/or reducing the overall dose.
*Median follow-up for MonumenTAL-1 cohorts: TCR-naïve Q2W is over 30 months, TCR-exposed is over 28 months, TCR-naïve QW is over 37 months.
aIncludes ageusia, dysgeusia, hypogeusia, and taste disorder.
bNail disorder includes: Koilonychia, nail bed disorder, nail cuticle fissure, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail pitting, nail ridging, nail toxicity, onychoclasis, onycholysis, and onychomadesis.
cSkin disorder includes: Palmar-plantar erythrodysaesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation, and skin fissures.
dIncludes 1 (0.6%) Grade 3/4 event for patients naïve to T-cell redirection therapy receiving TALVEY® Q2W.
eRash includes: Dermatitis, dermatitis acneiform, dermatitis contact, dermatitis exfoliative, dermatitis exfoliative generalized, erythema, exfoliative rash, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular, and stasis dermatitis.
fIncludes 12 (3.2%) Grade 3 events.
gXerosis includes: Dry eye and dry skin.
hIncludes 1 (0.3%) Grade 3/4 event.
iIncludes 13 (3.5%) Grade 3 event.

  1. TALVEY® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. U.S. FDA approves TALVEY® (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. Janssen Biotech, Inc.; August 10, 2023. Accessed November 10, 2025. https://www.jnj.com/media-center/press-releases/u-s-fda-approves-talvey-talquetamab-tgvs-a-first-in-class-bispecific-therapy-for-the-treatment-of-patients-with-heavily-pretreated-multiple-myeloma
  3. 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.
  4. Data on File. Janssen Biotech, Inc.
  5. Van de Donk N, Chari A, Martin T, et al. Cancer Medicine. Characterization and management of cytokine release syndrome from the MonumenTAL-1 study of talquetamab in patients with relapsed/refractory multiple myeloma. 2025. Online ahead of print.
  6. Schinke A, Rodriguez-Otero P, van de Donk N, et al. Blood Advances. Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1. 2025. Online ahead of print.
  7. Rasche L, Schicke C, Touzeau C, et al. Long-term efficacy and safety results from phase 1/2 MonumenTAL-1 Study of talquetamab, a GPRC5DxCD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. Poster. Presented at the European Hematology Association (EHA) 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.
AE Adverse event IgG Immunoglobulin G
ASTCT American Society for Transplantation and Cellular Therapy IMWG International Myeloma Working Group
BCMA B-cell maturation antigen LLN Lower limit of normal
C Cycle LTFU Long term follow-up
CAR-T Chimeric antigen receptor T-cell mDOR Median duration of response
CI Confidence interval MedDRA Medical Dictionary for Regulatory Activities
CNS Central nervous system mFU Median follow-up
COVID-19 Coronavirus disease 2019 MM Multiple myeloma
CR Complete response mTTCR Median time to complete response
CRS Cytokine release syndrome mTTR Median time to response
CTCAE Common Terminology Criteria for Adverse Events NE Not estimable
D Dose ORR Overall response rate
DOR Duration of response PFS Progression-free survival
eCRF Electronic Case Report Form PR Partial response
ECOG Eastern Cooperative Oncology Group QW Weekly
FDA U.S. Food and Drug Administration Q2W Every other week
GPRC5D G-protein-coupled receptor class C group 5 member D REMS Risk Evaluation and Mitigation Strategy
HGG Hypogammaglobulinemia sCR Stringent complete response
ICANS Immune effector cell-associated neurotoxicity syndrome TCR T-cell redirection therapies
IRC Independent Review Committee VGPR Very good partial response
J&J Medical Connect

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