The ASSIST CLAD study: A phase 2 randomized controlled trial of mesenchymal stromal cells for new-onset chronic lung allograft dysfunction.

BACKGROUND

Chronic lung allograft dysfunction (CLAD) remains the primary limitation to long-term survival after lung transplantation. We conducted a multicenter, phase 2, double-blind, randomized controlled trial of intravenous (IV) allogenic bone marrow-derived mesenchymal stromal cells (MSC) in lung transplant recipients with new-onset CLAD.

METHODS

Participants (bilateral or single lung transplant, aged ≥18 years, >6 months post-transplant and with a persistent fall in forced expiratory volume in 1 second [FEV1] and/or forced vital capacity [FVC] >20% from best post-transplant values within 12 months) were randomized (1:1, target n = 41 per arm) to receive MSC (2 × 10⁶ cells/kg IV twice weekly for 2 weeks) or placebo. The primary end-point was progression-free survival at 12 months, defined as a composite of all-cause mortality and freedom from CLAD progression (fall in FEV1 decline >10%).

RESULTS

Fifty-nine participants were randomized. Fifty-eight received treatment (31 placebo; 27 MSC). MSC treatment did not improve progression-free survival: Seventeen of 31 (55%) in the placebo arm vs 11 of 27 (41%) in the MSC arm (relative risk 0.74 (0.42-1.29), p = 0.30). Lung function decline was similar between groups. The FEV1 slope (95% CI) declined by 6.43 (-11.78, -1.08) ml/week in the MSC group and 9.14 (-14.29, -3.99) ml/week in the placebo group (difference: 2.56 (-4.88, 9.99) ml/week, p = 0.50). FVC declined by 4.58 (-7.51, -1.65) ml/week in the MSC group and by 4.19 (-6.97, -1.41) ml/week in the placebo group (difference: -0.39 (-4.43, 3.65) ml/week (p = 0.85).

CONCLUSIONS

MSC treatment did not influence progression-free survival in lung transplant recipients with new-onset CLAD.