Patients with severe, rapidly progressive diffuse interstitial lung disease (RP ILD) with anti-MDA5 have an appalling prognosis and the lack of effective medical treatment leads to lung transplantation being proposed as salvage treatment. Currently, transplant-free survival at 90 days (D90) is approximately 25%, dropping to less to 10% among those requiring mechanical ventilation. Peripheral lymphopenia and elevated anti-MDA5 antibody levels are associated with greater disease severity, highlighting the involvement of mature T and B lymphocytes in disease pathogenesis. Teclistamab, a bispecific antibody targeting the B-cell maturation antigen (BCMA) on plasma cells and engaging T cells - approved for the treatment of refractory multiple myeloma - has recently shown rapid and promising effects in patients with autoimmune conditions, including one MDA5-positive patient, while maintaining a favourable safety profile. We hypothesize that this bispecific antibody could represent a promising and safe therapeutic option for patients with severe MDA5-associated RP-ILD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Dosage and subcutaneous administration of Teclistamab: Day 1: 0.06 mg/kg Day 3: 0.3 mg/kg Day 5: 1.5 mg/kg)
The primary objective is to demonstrate the efficacy of teclistamab in improving transplant-free survival of patients with anti-Melanoma differentiation-associated protein 5 associated rapidly progressive diffuse interstitial lung disease.
The primary endpoint is transplant-free survival at 90 days, defined as the time from inclusion to lung transplantation or death from any cause.
Time frame: at 90 days
To assess the length of stay in hospital
Total hospital length of stay, from admission to discharge
Time frame: at 90 days
To evaluate disease severity
Disease severity evaluated using the World Health Organization Clinical Progression Scale adapted for Interstitial Lung Disease-associated respiratory failure (11-point ordinal scale from 0 to 10).
Time frame: at 90 days
To evaluate the response of Interstitial Lung Disease on imaging
Interstitial Lung Disease response will be based on evolution of Interstitial Lung Disease extent on centralized chest Computed Tomography at Day 0, Week 2, Week 4, Week 12 and Week 24
Time frame: From enrollment to the end at week 24
To assess the tolerance profile of teclistamab
Tolerance assessed by the occurrence and gradation of adverse events, including infections complications detected by microbiological monitoring protocolised in ICU units during the follow-up period.
Time frame: to day 1 of treatment to the end of treatment (4 week )
To evaluate the response of extra-respiratory manifestations including muscular involvement
Dermatomyositis disease monitoring assessed at Day 0, Week 2, Week 4, Week 12 and Week 24 through: Manual Muscle Testing 8 score (set of 8 designated muscles tested unilaterally)
Time frame: From Day 0 at week 24
To evaluate overall survival
Overall Survial defined as the time from inclusion to death from any cause, with documentation of the causes of death.
Time frame: from inclusion to day 90
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