Clinical trialPhase 1-2Blood cancers (leukaemia, lymphoma and myeloma)Multiple myeloma

Teclistamab in Relapsed or Refractory Multiple Myeloma

N Engl J Med · 2022165 patients

Moreau P, Garfall AL, van de Donk NWCJ, et al. N Engl J Med. 2022. 387:495-505

Study type: Clinical trial
Study name: MajesTEC-1
Phase: Phase 1-2
Design: Single-arm, open-label, multicentre study (NCT03145181 and NCT04557098)
Sample size: 165 patients
Source: N Engl J Med · 2022
Trial registration: NCT03145181

In plain words

Teclistamab is a "two-armed" (bispecific) antibody that links the patient's immune T cells to myeloma cells. Unlike CAR-T, this drug is ready-made and is given as a weekly injection under the skin. In patients for whom on average 5 earlier treatments had failed, about 6 out of 10 responded, and the responses were often long-lasting. The most important safety point is a high risk of infection, so infection prevention, vaccination and sometimes immunoglobulin infusions are recommended.

Key results

63.0%

Overall response rate

Median follow-up 14.1 months

39.4%

Complete response or better

65 patients; MRD negativity in 26.7% of all patients

18.4 months

Median duration of response

95% CI 14.9 to not estimable

11.3 months

Median progression-free survival

95% CI 8.8–17.1

Dose and schedule cards

Teclistamab monotherapy (MajesTEC-1)

Relapsed or refractory multiple myeloma after at least 4 lines of therapy including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibodyCycle length: WeeklyOn the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in multiple myeloma

Relapsed or refractory multiple myeloma after at least 4 lines of therapy including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody

Drug	Dose	Route	Schedule
Step-up dosing
Teclistamab	0.06 mg/kg (Day 1), 0.3 mg/kg (Day 4), 1.5 mg/kg (Day 7)	SC	Days 1, 4 and 7
Continuation
Teclistamab	1.5 mg/kg weekly (after at least 6 months of complete response or better: every 2 weeks)	SC	Weekly

Cycle length: Weekly
Duration: Until progression or unacceptable toxicity

1 to 3 hours before each step-up dose: dexamethasone 16 mg, diphenhydramine 50 mg and acetaminophen 650 to 1,000 mg. Hospitalisation for 48 hours after step-up doses 1 and 2. Antiviral prophylaxis against herpes zoster may be considered. The combination of teclistamab with subcutaneous daratumumab for patients after at least 1 line of therapy is also included in the label.

On the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in multiple myeloma

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Subcutaneous teclistamab

Teclistamab subcutaneously: step-up doses of 0.06 mg/kg (day 1) and 0.3 mg/kg (day 4; 2 to 4 days after the previous dose) and a first treatment dose of 1.5 mg/kg (day 7), then 1.5 mg/kg weekly until disease progression or unacceptable toxicity. According to the current label: in patients with a complete response or better for at least 6 months, the interval is extended to every 2 weeks; hospitalisation for 48 hours after step-up doses 1 and 2; premedication 1 to 3 hours before the step-up doses and the first treatment dose (dexamethasone 16 mg, diphenhydramine 50 mg, paracetamol [acetaminophen] 650 to 1000 mg).

Source of the regimen details: Abstract of the paper (step-up doses of 0.06 and 0.3 and a dose of 1.5 mg/kg weekly); dosing days, reduced frequency, hospitalisation and premedication from the FDA label for TECVAYLI (2026 version)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with relapsed or refractory multiple myeloma after at least three lines of therapy, including exposure to three drug classes (an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody). 77.6% were triple-class refractory; median of five prior lines of therapy.

Endpoints

Primary endpoint: overall response (partial response or better).

Secondary endpoints: complete response, MRD, duration of response, progression-free survival and safety.

Safety and side effects

Cytokine release syndrome 72.1% (grade 3: 0.6%; no grade 4). Neurotoxic events 14.5%, including ICANS 3.0% (all grade 1 or 2). Neutropenia 70.9% (grade 3 or 4: 64.2%), anaemia 52.1% (grade 3 or 4: 37.0%), thrombocytopenia 40.0% (grade 3 or 4: 21.2%). Infections were common: 76.4% (grade 3 or 4: 44.8%).

Clinical significance and place in guidelines

Based on this study, in October 2022 the FDA granted accelerated approval to teclistamab (Tecvayli) for relapsed or refractory myeloma after at least four prior lines of therapy (including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody), and the EMA also approved it. It was the first approved anti-BCMA bispecific antibody. The current FDA label also includes teclistamab combined with subcutaneous daratumumab (based on the phase 3 MajesTEC-3 trial), which has brought this drug into earlier lines.

Limitations

The study is single-arm with no comparison group. Severe infections (including opportunistic infections) and hypogammaglobulinaemia are common with continuous therapy. Patients with prior anti-BCMA therapy were not included in this cohort.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.