Teclistamab: real-world safety and efficacy

Teclistamab is a T-cell directed bispecific antibody that binds to CD3 and B-cell maturation antigens on plasma cells. Results from the phase II part of the MajesTEC-1 trial (NCT04557098) resulted in the approval of teclistamab by the U.S. Food and Drug Administration (FDA) in October 2022 for the treatment of relapsed/refractory multiple myeloma. While results from the trial were positive, the stringent inclusionary criteria limited the representation of real-world patients, who commonly present organ dysfunction, significant comorbidities, and high-risk disease characteristics.

During the 65th American Society of Hematology Annual Meeting and Exposition, Dima presented results from a retrospective analysis to evaluate the real-world safety and efficacy of teclistamab, with a focus on patients who would have been ineligible for the MajesTEC-1 trial. We summarize the key findings below.

Check out our top abstracts presented at the 65th ASH Annual Meeting and Exposition here. For more information on the incidence and management of infections in patients enrolled in the MajesTEC-1 trial, read our previous Multiple Myeloma Hub article.

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Study design¹

• The full study design of the MajesTEC-1 trial was reported in this Multiple Myeloma Hub article.
• This study was a retrospective multicenter analysis of the expanded-access program for teclistamab, which took place between August 2022 and August 2023.
• All patients had received at least one full dose of teclistamab as of July 15, 2023
• The data cutoff was August 15, 2023.

Results¹

• The baseline patient characteristics and reasons for MajesTEC-1 ineligibility are shown in Table 1.

Table 1. Baseline patient characteristics and reasons for MajesTEC-1 ineligibility*

ASCT, autologous stem cell transplant; BCMA, B-cell maturation antigen; CNS, central nervous system; ECOG, European Cooperative Oncology Group; EMD, extramedullary disease; R-ISS, Revised International Scoring System. *Adapted from Dima, et al.1
Characteristic, % (unless otherwise specified)	N = 106
Median age, years	66.5
Median time since diagnosis, years	5.5
Median number of prior lines of therapy, n	6
>4 prior lines of therapy	80
R-ISS stage III	31
ECOG performance status ≥2	33
EMD	42
High-risk cytogenetics	59
Prior BCMA therapy	53
Reasons for MajesTEC-1 ineligibility, % (unless otherwise specified)	n = 88
Prior anti-BCMA therapy	53
Poor performance status (ECOG ≥2)	33
Any baseline cytopenia	31
Renal dysfunction	13
Liver dysfunction	5
Cardiac dysfunction	4
Plasma cell leukemia	2
Amyloidosis	1
CNS involvement	4
ASCT ≤12 weeks	1

• A total of 56 patients had received prior B-cell maturation antigen therapy

Efficacy¹

• The real-world efficacy results of teclistamab are shown in Figure 1.

CR, complete response; ORR, overall response rate; PR, partial response; VGPR, very good PR.
*Adapted from Dima, et al.¹

• The overall response rates (ORR) according to the type of previous therapy are shown in Table 2.

Table 2. ORR according to previous therapy*

ADC, antibody-drug conjugate; CAR T-cell, chimeric antigen receptor T-cell; ORR, overall response rate. *Adapted from Dina, et al.1
Type of previous therapy	ORR	Number of patients
ADC	50	10
CAR T cell	57	33
ADC + CAR T cell	80	10
ADC + other	33	3

• Median follow-up time was 3.8 months.
• Median progression-free survival (PFS) was 5.4 months.
• Median overall survival (OS) was not reached:
  • 6-month OS rate 70%; and
  • 10-month OS rate 67%.
• Multivariate analysis revealed several factors were independently associated with inferior ORR; these were:
  • European Cooperative Oncology Group (ECOG) performance score ≥2;
  • extramedullary disease; and
  • >4 prior lines of therapy.
• Factors independently associated with inferior PFS were:
  • ECOG performance score ≥2;
  • extramedullary disease; and
  • age ≤70 years.

Safety¹

• Cytokine release syndrome of any grade was experienced by 64% of patients, with a median duration of 1 day.
• Immune effector cell-associated neurotoxicity of any grade was experienced by 14% of patients, with a median duration of 2 days.
• The percentage of patients who experienced hematological adverse events of any grade at Days 30 and 90 are shown in Figure 2.

*Adapted from Dina, et al.¹

• A total of 39 infections were reported, of which 46% were serious.
• In total, 29 patients died during the study.
  • The main cause of death was disease progression (86%).

Conclusion¹

Teclistamab demonstrated efficacy and favorable tolerability in the real-world setting, especially in patients with heavily pretreated relapsed/refractory disease. The ORRs were similar to those reported in the MajesTEC-1 trial. However, lower rates of complete response or better were seen in this setting. Extramedullary disease and ECOG performance score independently predicted worse OS and PFS. Incidences of severe cytokine release syndrome and immune cell-associated neurotoxicity were minimal. Future research should explore the risk-benefit balance of shorter treatment durations and potential cessation in patients achieving deep remission to support immune recovery.

This educational resource is independently supported by Johnson & Johnson . All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.