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Talquetamab receives breakthrough therapy designation from the FDA

Jul 4, 2022
Learning objective: After reading this article, learners will be able to cite a new clinical development in relapsed/refractory MM

On the June 29, 2022, talquetamab was granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for use in patients with relapsed/refractory multiple myeloma.1 At the European Hematology Association (EHA)2022 Congress, updated safety and efficacy data from the phase I/II MonumenTAL-1 trial (NCT03399799 and NCT04634552) were presented by Monique Minnema,2 and we are pleased to provide a summary of this presentation here.

Talquetamab is an off-the-shelf bispecific antibody that targets GPRC5D on myeloma cells and CD3 on T cells. One of the benefits of this drug is that it is administered subcutaneously rather than intravenously, which can be less distressing for patients. The Multiple Myeloma Hub has previously reported on the characteristics of GPRC5D and the mechanism of action of talquetamab; you can find the article here.

Latest data from the MonumenTAL-1 trial

The updated results of the MonumenTAL-1 trial include a longer follow-up of patients treated with talquetamab at the recommended phase II dose (405 µg/kg), with additional data from patients dosed at 800 µg/kg. Key patient characteristics are shown in Table 1.

Table 1. Patient characteristics*

Characteristic, % (unless otherwise stated)

Pts dosed at 405 µg/kg
(n = 30)

Pts dosed at 800 µg/kg
(n = 44)

Median age (range), years

61.5 (4680)

64 (4784)




High-risk cytogenetics



ISS stage












Median prior lines of therapy (range), n

6 (214)

5 (217)

Prior stem cell transplantation



Refractory status









              BCMA-targeted ADC or BsAb



ADC, antibodydrug conjugate; BCMA, B-cell maturation antigen; BsAb, bispecific antibody; IMiD, immunomodulatory drug; ISS, International Staging System; mAb, monoclonal antibody; PI, proteasome inhibitor; Pts, patients.
*Adapted from Minnema, et al.2
≥1 PI, ≥1 IMiD, and ≥1 anti-CD38 mAb.
≥2 PIs, ≥2 IMiDs, and ≥1 anti-CD38 mAb.


A step-up dosing regimen was followed to mitigate against severe cytokine release syndrome (CRS). Patients were given 23 step-up doses prior to the first full dose. In addition, a glucocorticoid, antihistamine, and antipyretic were given as premedication prior to the step-up doses and first full dose.

  • The most common hematologic adverse events (AEs) of any grade were as follows:
    • Neutropenia, which occurred in 66.7% of patients dosed at 405 µg/kg and 40.9% of patients dosed at 800 µg/kg.
    • Anemia, which occurred in 56.7% of patients dosed at 405 µg/kg and 47.7% of patients dosed at 800 µg/kg.
    • Other cytopenias, including lymphopenia, leukopenia, and thrombocytopenia, which occurred at similar incidence rates and were mostly confined to initial cycles.
  • Any grade CRS occurred in 76.7% of patients dosed at 405 µg/kg and 79.5% of patients dosed at 800 µg/kg.
  • Other frequent nonhematologic AEs of any grade were skin-related, dysgeusia, dry mouth, and nail- and rash-related.
  • Any grade infections occurred in 46.7% of patients dosed at 405 µg/kg and 38.6% of patients dosed at 800 µg/kg.
  • No deaths due to drug-related AEs were recorded.


  • The median follow-up was 13.2 months for the patients dosed at 405 µg/kg and 7.7 months for the patients dosed at 800 µg/kg.
  • The overall response rate (ORR) was comparable across both dosing cohorts, with an ORR of 70.0% and 63.6% for 405 µg/kg and 800 µg/kg, respectively. Response rates are shown in Figure 1.
  • To date, the median duration of response has been reported to be 10.2 months and 13.0 months for the 405 µg/kg and 800 µg/kg cohorts, respectively; however, this trial is ongoing and responses that deepen over time have been recorded.
  • Significant response rates have also been reported in the triple-drug and penta-class refractory subgroups at both dose levels.
    • At 405 µg/kg, the ORR was 65.2% and 67.6% for triple-drug- and penta-class-refractory patients, respectively
    • At 800 µg/kg, the ORRs were higher, with 83.3% of patients with triple-drug refractory disease and 75.0% of patients with penta-class refractory disease achieving at least a partial response.

Figure 1. Overall response rates for patients treated with 405 µg/kg or 800 µg/kg talquetamab*

CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
*Adapted from Minnema, et al.2


The updated results from this study show a promising safety and efficacy profile of talquetamab at the doses of 405 µg/kg and 800 µg/kg. Only one case of Grade 3 CRS was reported at the dose of 405 µg/kg, and no cases of Grade 3 CRS were reported with 800 µg/kg. This, alongside the promising ORRs observed, suggests talquetamab could be used for patients with relapsed/refractory multiple myeloma who have progressed to multiple lines of therapy, including patients previously exposed to B-cell maturation antigen-directed agents.

  1. Janssen. Janssen announces U.S. FDA breakthrough therapy designation granted for talquetamab for the treatment of relapsed or refractory multiple myeloma. Published Jun 29, 2022. Accessed Jun 30, 2022.

  2. Minnema M. Talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in relapsed/refractory multiple myeloma: updated efficacy and safety results from MonumenTAL-1. Oral abstract #S182. European Hematology Association 2022 Congress; Jun 11, 2022; Vienna, AT.