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TECVAYLI®

(teclistamab-cqyv)

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TECVAYLI® (teclistamab-cqyv)

Medical Information

TECVAYLI - Use in Elderly Patients

Last Updated: 02/05/2025

SUMMARY

  • Janssen does not recommend any practices, procedures or usage that deviate from the product labeling or are not approved by the regulatory agencies.
  • MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the efficacy and safety of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).1-3
    • Cohort A (triple-class exposed) included 165 patients with RRMM who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.3
      • Costa et al (2024)4 presented a subgroup analysis of the MajesTEC-1 study, evaluating the efficacy and safety in patients with high-risk (HR) features, including patients ≥75 years of age. As of the data cutoff on August 22, 2023, the overall response rate (ORR) was 63% in all patients and 54.2% in patients ≥75 years of age. Any-grade treatment-emergent adverse events (TEAEs) were reported in 100% of patients ≥75 years of age; 87.5% of TEAEs were grade 3/4.
  • Pasvolsky (2024)5 presented a retrospective, multicenter study of real-world outcomes of a large cohort of elderly patients (<75 years and ≥75 years) with RRMM receiving standard-of-care (SOC) TECVAYLI treatment.
  • Dima et al (2023)6 evaluated the efficacy and safety of TECVAYLI in patients >70 years of age compared to those ≤70 years of age in a retrospective, real-world study.
  • Dieterle et al (2023)7 described the use of TECVAYLI in 3 patients, >80 years of age, with RRMM who received ≥3 prior lines of therapy (LOTs).

CLINICAL DATA - MAJESTEC-1 STUDY

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: NCT03145181, NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.1-3

Study Design/Methods

  • The main objectives are as follows: part 1 (dose escalation), to determine the recommended phase 2 dose (RP2D) for TECVAYLI; part 2 (dose expansion), to distinguish safety and tolerability at RP2D; and part 3 (phase 2 component), to evaluate the efficacy of TECVAYLI at RP2D.3,8
  • Key eligibility criteria:
    • Cohort A: received ≥3 prior LOTs (including a PI, an immunomodulatory drug, and an anti-CD38 mAb) and no prior B-cell maturation antigen (BCMA)-targeted therapy use.3
  • Primary endpoint for Cohort A: ORR.3
  • Key secondary endpoint for Cohort A: safety.3

Cohort A

Costa et al (2024)4 presented a subgroup analysis from the MajesTEC-1 study evaluating the efficacy and safety in patients with HR features. Results specific to patients ≥75 years of age are summarized below.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

  • By the data cutoff date of August 22, 2023, a total of 165 patients had received TECVAYLI at the RP2D; 24 patients (14.5%) were aged ≥75 years.

Efficacy


MajesTEC-1 Study (Cohort A): Summary of ORR4
Overall RP2D
(N=165)
Age ≥75 Years
(n=24)
ORRa, n/N (%)
104/165 (63.0)
13/24 (54.2)
   sCR, %
38.8
37.5
   CR, %
7.3
4.2
   VGPR, %
13.3
8.3
   PR, %
3.6
4.2
≥CR, %
46.1
41.7
Abbreviations: CR, complete response; ORR, overall response rate; PR, partial response; RP2D, recommended phase 2 dose; sCR, stringent complete response; VGPR, very good partial response.
Note: Clinical data cutoff date of August 22, 2023.
aResponse assessed by an independent review committee.

MajesTEC-1 Study (Cohort A): DOR to TECVAYLI4
Overall RP2D
(N=165)
Age ≥75 Years
(n=24)
Responders, n
104
13
mFU, months (range)
30.4 (0.3-41.5)
29.5 (1.5-32.9)
24-month DOR rate, % (95% CI)
50.1 (40.1-59.4)
53.8 (24.8-76.0)
Abbreviations: CI, confidence interval; DOR, duration of response; mFU, median follow-up; RP2D, recommended phase 2 dose.
Note: Clinical data cutoff date of August 22, 2023. Results should be interpreted with caution due to small patient numbers.

Safety


MajesTEC-1 Study (Cohort A): Summary of Safety Outcomes4
Overall RP2D
(N=165)
Age ≥75 Years
(n=24)
Any-grade TEAEs, n (%)
165 (100)
24 (100)
   Grade 3/4 TEAEs
156 (94.5)
21 (87.5)
Discontinuation due to TEAE, n (%)
8 (4.8)
0
Deaths, n (%)
94 (57.0)
15 (62.5)
   Due to AE
26 (15.8)
5 (20.8)
   Due to disease progression
56 (33.9)
9 (37.5)
Abbreviations: AE, adverse event; RP2D, recommended phase 2 dose; TEAE, treatment-emergent adverse event.
Note: Clinical data cutoff date of August 22, 2023. Results should be interpreted with caution due to small patient numbers.

Real-world data

Pasvolsky et al (2024)5 presented a retrospective, multicenter study of a large cohort of elderly patients (<75 years and ≥75 years) with RRMM receiving SOC TECVAYLI treatment.

Study Design/Methods

  • This retrospective, multicenter study included data of patients with RRMM who received SOC TECVAYLI at 13 centers of the United States (US) Multiple Myeloma Immunotherapy Consortium with a data cutoff date was April 30, 2024.
  • Patients included in this study were divided into the following groups: age <75 years and age ≥75 years.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

  • A total of 302 patients and 83 patients were included in the <75-year and ≥75-year age groups, respectively. Baseline characteristics of these patients are presented in Table: Baseline Patient Characteristics.

Baseline Patient Characteristics5
Characteristic
Age Group
P-Value
<75 Years
(N=302)
≥75 Years
(N=83)
Age, years, median (range)
65 (31-74)
78 (75-92)
-
Male, n (%)
163 (54)
40 (48)
0.35
Race, White, n (%)
190 (63)
65 (78)
0.01
ECOG ≥2, n (%)
65 (24)
23 (29)
0.37
MajesTEC-1 noneligible, n (%)
241 (80)
60 (73)
0.20
Baseline CrCl <30 mL/min, n (%)
34 (11)
11 (14)
0.59
Baseline LDH >ULN, n (%)
120 (46)
34 (43)
0.58
High-risk cytogeneticsa, n (%)
175 (58)
37 (45)
0.03
Double-hit myelomab, n (%)
71 (24)
10 (12)
0.02
Bone marrow PCs >50%, n (%)
71 (24)
10 (12)
0.02
EMD at baseline, n (%)
121 (40)
18 (22)
0.002
Prior LOTs, median (range)
6 (2-18)
6 (2-14)
-
Triple-class refractory, n (%)
257 (85)
63 (77)
0.06
Penta-class refractory, n (%)
118 (39)
24 (30)
0.15
Prior autologous transplant, n (%)
218 (72)
35 (43)
<0.0001
Prior anti-BCMA agent, n (%)
166 (55)
27 (33)
0.0003
Prior anti-GPRC5D agent, n (%)
9 (3)
2 (2.4)
1.00
Abbreviations: BCMA, B-cell maturation antigen; CrCl, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; EMD, extramedullary disease; GPRC5D, G protein-coupled receptor class C group 5 member D; LDH, lactate dehydrogenase; LOT, line of therapy; PC, plasma cell; ULN, upper limit of normal.
aDefined as a del(17p), t(4;14), or t(14;16) and/or gain or amplification of 1q21 abnormality.
bDefined as having 2 high-risk cytogenetic abnormalities.

Efficacy


Summary of Efficacy Response5
Parameter
Age Group
P-Value
<75 Years
(N=302)
≥75 Years
(N=83)
ORR, n/N (%)
161/301 (53.0)
50/81 (62)
0.05
   CR/sCR, %
22
28
-
   PR, %
9
9
-
   VGPR, %
22
25
-
≥VGPR, %
44
53
0.1
Median PFS, months
5.2
10.72
0.005
Median OS, months
16.1
NR
0.0479
Abbreviations: CR, complete response; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.

Multivariable Analysis of Survival Outcomes (<75 Years vs ≥75 Years): PFS and OS5 
Parametera
Hazard Ratio (95% CI)
P-Value
PFS
1.15 (0.72-1.84)
0.55
OS
1.67 (0.84-3.33)
0.15
Abbreviations: ALC, absolute lymphocyte count; BCMA, B-cell maturation antigen; CI, confidence interval; CrCl, creatinine clearance; CRP, C-reactive protein; ECOG, Eastern Cooperative Oncology Group; EMD, extramedullary disease; GPRC5D, G protein-coupled receptor class C group 5 member D; LDH, lactate dehydrogenase; LOT, line of therapy; PCL, plasma cell leukemia.
aVariables considered from univariate analysis included age, gender, race, high-risk cytogenetics, double-hit, number of prior LOTs, triple/penta-refractoriness status, prior autologous transplant, prior anti-BCMA agent, prior anti-GPRC5D agent, CrCl <30 mL/min, LDH, ECOG, MajesTEC-1 eligibility, ferritin, CRP, platelets, hemoglobin, ALC, albumin, EMD, PCL, accelerated step-up dosing, and bone marrow plasma cells.

Safety

  • All-grade CRS events were reported in 59% of patients (n=177) in the <75-year age group and in 52% of patients (n=43) in the ≥75-year age group. See Table: Summary of CRS Events for additional details.
  • All-grade ICANS events were reported in 13% of patients (n=38) in the <75-year age group and in 19% of patients (n=16) in the ≥75-year age group. See Table: Summary of ICANS Events for additional details.
  • Causes of deaths reported in the study population are detailed in Table: Causes of Death.

Summary of CRS Events5
Parametera
Age Group
P-Value
<75 Years
(N=302)
≥75 Years
(N=83)
Patients with any grade CRS event, n (%)
177 (59)
43 (52)
0.2674
   Grade 2-4
33 (11)
8 (10)
0.7361
Maximum toxicity grade, n (%)
   Grade 1
144 (48)
35 (42)
-
   Grade 2
30 (10)
7 (8)
-
   Grade 3
2 (0.7)
1 (1)
-
   Grade 4
1 (0.3)
0
-
   Any grade
177 (59)
43 (52)
0.2674
Median time to CRS onset, days (range)
3 (0-15)
3 (0-8)
0.5951
Median time to maximum CRS, days (range)
3 (0-17)
3 (0-8)
0.6217
Received tocilizumab, n (%)
121 (40)
26 (31)
0.5420
Received steroids, n (%)
53 (18)
14 (17)
0.6422
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome.
aCRS was graded according to the ASTCT consensus grading.

Summary of ICANS Events5 
Parametera
Age Group
P-Value
<75 Years
(N=302)
≥75 Years
(N=83)
Patients with any grade ICANS Event, n (%)
38 (13)
16 (19)
0.1198
   CRS (grade 2-4) and/or ICANS (any grade)
63 (21)
19 (23)
0.6890
Maximum toxicity grade, n (%)
   Grade 1
17 (6)
9 (11)
-
   Grade 2
14 (5)
4 (5)
-
   Grade 3
7 (2)
3 (4)
-
Median time to ICANS onset, days (range)
4 (0-21)
3 (0-25)
0.8862
Median time maximum ICANS, days (range)
5 (0-22)
4 (0-25)
0.2275
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome.
aICANS was graded according to the ASTCT consensus grading.

Causes of Death5
Parameter
Age Group
<75 Years
(N=118)
≥75 Years
(N=20)
Median follow-up, months (95% CI)
10.4 (9.9-11.2)
8.7 (7.6-9.9)
Myeloma progression, n (%)
89 (75)
14 (70)
Infection, n (%)
12 (10)
5 (25)
   Sepsis
6 (5)
2 (10)
   Pneumonia
5 (4)
3 (15)
   N/A
1 (1)
0
Other malignancy, n (%)
6 (5)
0
Other/unknown, n (%)
11 (9)
1 (5)
Death within 3 months, n (%)
74 (25)
12 (15)a
Death within 6 months, n (%)
93 (31)
18 (22)b
Abbreviations: CI, confidence interval; N/A, not available.
aP-value=0.05.
bP-value=0.1.

Dima et al (2023)6 presented efficacy and safety data from a retrospective, real-world study evaluating the use of TECVAYLI in older patients (>70 years) with RRMM compared to younger patients (≤70 years).  

Study Design/Methods

  • The study population consisted of patients with RRMM who received TECVAYLI as of July 1, 2023 at 5 US academic centers, part of the US Myeloma Innovations Research Collaboration.
  • Outcomes assessed included ORR, complete response or better (≥CR), and safety. Responses were assessed using the International Myeloma Working Group (IMWG) criteria.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

  • A total of 102 patients were included in the study, including 33 patients (32%), who were >70 years of age and 69 (68%) who were ≤70 years of age.
  • Additional baseline characteristics are summarized in Table: Baseline Characteristics.4

Baseline Characteristics4
Characteristic
Age >70 years
(n=33)
Age ≤70 years
(n=69)
Age, years, median (range)
75 (71-87)
62 (35-70)
ECOG PS >2, n (%)
15 (45)
18 (26)
Prior LOT (median, range)
6 (4-17)
6 (4-14)
High risk cytogenetics, n (%)
19 (58)
36 (52)
Extramedullary disease, n (%)
13 (39)
31 (45)
Prior autologous stem cell transplant, n (%)
19 (58)
41 (59)
Triple refractory disease, n (%)
32 (97)
62 (90)
Penta refractory disease, n (%)
19 (58)
49 (71)
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group Performance Status; LOT, line of therapy.

Efficacy

  • At a median follow-up of 3.2 months, ORR (70% vs 61%, P=0.37) and ≥CR (30% vs 28%, P=0.8) were comparable in patients >70 years vs ≤70 years.
  • Median estimated progression-free survival was 5.4 vs 3.8 months in patients >70 years vs ≤70 years respectively (P=0.61).

Safety


Safety Outcomes for Patients >70 Years of Age vs Patients ≤70 Years of Age4
Safety Outcome, n (%)
Age >70 years
(n=33)
Age ≤70 years
(n=69)
P-Value
CRS, any grade  
22 (67)
44 (64)
0.7
CRS, >grade 3
1 (3)
0 (0)
0.2
ICANS  
7 (21)
8 (11)
0.17
ICANS, >grade 3  
0 (0)
3 (4)
0.2
Neutropenia, grade 3-4
8 (24)
15 (22)
0.82
Anemia, grade 3-4
7 (21)
11 (16)
0.53
Thrombocytopenia, grade 3-4
9 (27)
8 (12)
0.05
Infection
11 (33)
18 (26)
0.46
Hospital readmission
12 (36)
16 (23)
0.16
Abbreviations: CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity. Adverse events graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria

CLINICAL DATA - case reports

Dieterle et al (2023)7 reported on the efficacy and safety of TECVAYLI administered at the recommended dosing schedule in patients (N=3) aged >80 years after ≥3 prior LOT. A case report of an octogenarian is summarized below.

  • Disease characteristics: An elderly patient (80 years) presented with initial cervical pain and high lambda free serum light chains (FSLCs). The patient fulfilled 3 of 4 CRAB criteria (hypercalcemia, renal dysfunction, anemia, and bone lesions) and was diagnosed with multiple myeloma. Bone marrow biopsy revealed 80% plasma cell infiltration and unfavorable cytogenetics (t[11;14]; monosomy 13; CKS1B gene amplification in 1q21).
  • Treatment: After an initial course of radiation, the patient received a first LOT of bortezomib-cyclophosphamide-dexamethasone (5 cycles), a second LOT of daratumumab-lenalidomide-dexamethasone (10 cycles), and a third LOT of daratumumab-pomalidomide-dexamethasone (6 cycles). Prior to TECVAYLI initiation, bridging therapy with cyclophosphamide and dexamethasone was administered to limit disease progression. At the age of 82 years, the patient received step-up doses of TECVAYLI subcutaneously (SC; day 1, 0.06 mg/kg; day 3, 0.3 mg/kg, and day 5, 1.5 mg/kg) in cycle 1. Subsequent TECVAYLI doses (1.5 mg/kg SC weekly) were administered in an outpatient setting.
  • Response: The patient achieved complete remission (lambda FSLCs <0.5 mg/L, immunofixation negativity in serum and urine) 1 and 2 months after TECVAYLI initiation.
  • Safety: Hematologic adverse events were reported as Grade 1 pancytopenia. No CRS or ICANS events were reported.

Two additional patients >80 years suffering from symptomatic RRMM after proteosome inhibitor, immunomodulatory agent, and anti-CD38 mAb therapy were treated with TECVAYLI. Data on disease characteristics, treatment duration, response, and safety are summarized in the Table: Detailed Patient Characteristics of Octogenarians Treated With TECVAYLI.9


Detailed Patient Characteristics of Octogenarians Treated With TECVAYLI9
#a
MM Type
ID of MM
Prior # of LOT
Age at TECVAYLI Start
Symptoms Before TECVAYLI
TECVAYLI Tolerance
Safety
TECVAYLI Cycle #
TECVAYLI
Treatment Duration (weeks)
Ongoing Outpatient Treatment
Responseb
R-MCIc Change Before: on TECVAYLI Treatment
1
λ LC
7/2021
3
82 years
CRAB: 4/4
++: CRS: 0, ICANS: 0
11
12
Yes
CR
7/9  5/9: frail  intermediate-fit
2
IgA κ
6/2018
4
87 years
CRAB: 2/4
++: CRS: 2, ICANS: 0
6
7
Yes
VGPR
6/9  5/9: intermediate-fit
3
λ LC
11/2021
4
84 years
CRAB: 2/4
++: CRS: 1, ICANS: 0
4
5
Yes
VGPR
4/9  2/9: intermediate-fit  fit
Abbreviations: #, number; κ, kappa; λ, lambda; CR, complete response; CRAB, hypercalcemia, renal impairment, anemia, bone lesions; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; ID, initial diagnosis; IMWG, international myeloma working group; IgA, Immunoglobulin A;  LC, light chain; LOT, line of therapy; MM, multiple myeloma; R-MCI: revised myeloma comorbidity index; VGPR, very good partial response.aPatient identification number bAccording to IMWG criteria.cMyeloma comorbidity index: www.myelomacomorbidityindex.org/en_calc.html.

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 31 January 2025.

 

References

Show
1 Janssen Research & Development, LLC. A phase 1, first-in-human, open-label, dose escalation study of teclistamab, a humanized BCMA x CD3 bispecific antibody in subjects with relapsed or refractory multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 January 31]. Available from: https://clinicaltrials.gov/study/NCT03145181 NLM Identifier: NCT03145181.  
2 Janssen Research & Development, LLC. A phase 1/2, first-in-human, open-label, dose escalation study of teclistamab, a humanized BCMA x CD3 bispecific antibody, in subjects with relapsed or refractory multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 January 31]. Available from: https://clinicaltrials.gov/study/NCT04557098 NLM Identifier: NCT04557098.  
3 Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505.  
4 Costa LJ, Bahlis NJ, Usmani SZ, et al. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma with high-risk features: a subgroup analysis from the phase 1/2 MajesTEC-1 study. Poster presented at: European Hematology Association (EHA) 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.  
5 Pasvolsky O, Dima D, Feng L, et al. Outcomes of elderly patients with relapsed refractory multiple myeloma (RRMM) treated with teclistamab: A multicenter study from the US Multiple Myeloma lmmunotherapy Consortium. Oral Presentation presented at: The 65th American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024; Rio de Janeiro, Brazil.  
6 Dima D, Sanareddy A, Ahmed N, et al. Toxicity and efficacy outcomes of teclistamab in patients with relapsed-refractory multiple myeloma above the age of 70 Years: a multicenter study. Poster Presentation presented at: 65th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA.  
7 Dieterle M, Mostufi-Zadeh-Haghighi G, Kus J, et al. Safe and successful teclistamab treatment in very elderly multiple myeloma (MM) patients: a case report and experience from a total of three octogenarians. [published online ahead of print, Sep 15, 2023]. Ann Hematol. 2023. doi:10.1007/s00277-023-05451-8.  
8 Moreau P, Garfall AL, van de Donk NWCJ, et al. Protocol to: Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505.  
9 Dieterle MP, Mostufi-Zadeh-Haghighi G, Kus JW, et al. Safe and successful teclistamab treatment in very elderly multiple myeloma (MM) patients: a case report and experience from a total of three octogenarians[Supplement]. [published online ahead of print, Sep 15, 2023]. Ann Hematol. 2023:1-3. doi:10.1007/s00277-023-05451-8.