Alemtuzumab (AL) for Rapidly Progressive Chronic Lung Allograft Dysfunction (RP-CLAD): A Single-Center Experience

Document Type

Conference Proceeding

Publication Date

4-2026

Publication Title

Journal of Heart and Lung Transplantation

Abstract

Purpose: There are limited therapeutic options for RP-CLAD. Small case series have reported a slowing in the decline of lung function. We sought to review our center’s experience with AL.

Methods: Consecutive lung transplant recipients from Sept 2017 - Dec 2024 with RP-CLAD, defined as a decline in FEV1 > 30 ml/m in the preceding 6 m, treated with AL were included. The primary objective was to compare the change in slope of the forced expiratory volume in 1 second (ΔFEV1 slope) in the 6 m prior vs. after administration of AL. Subjects who died or were retransplanted within 6 m were given a ΔFEV1 slope of 0. A therapeutic response was defined as a > 50% decrease in the ΔFEV1 slope. Factors associated with treatment response were explored.

Results: Twenty-seven recipients (16 male, 25 white, 25 bilateral) with median age of 67 (IQR: 63, 69) were treated with a single 30 mg subcutaneous dose of AL at median post-transplant time of 3 yrs (1.8, 4.7). Underlying diagnosis group was A in 12, D in 9, C in 4 and B in 2. Baseline CLAD stage was 1 in 6 patients, 2 in 7, 3 in 13 and 4 in 1. Median FEV1 was 72% (47, 93) of predicted. CLAD phenotype was obstructive in 21, restrictive in 2 and mixed in 4. Treatment was well tolerated with no acute serious adverse events. The median FEV1 slope in the 6 m prior to AL was - 217 ml/m (-280, -92). AL was associated with a significant slowing in FEV1 decline with a slope of - 19 ml/m (-79, +10) in the 6 months post-therapy (ΔFEV1 slope: + 158 ml/m [+55, +250); P < 0.001 by Wilcoxon paired test). 21 (78%) experienced a therapeutic response at 6 m. During a median follow-up time of 3.8 yr, 15 patients died or were retransplanted due to graft failure 0.9 yr (0.5, 2.1) post-AL. K-M estimates of 1- and 3-yr transplant-free survival were 60% and 40%, respectively. There was a strong correlation between the pre-AL FEV1 slope and ΔFEV1 slope (rho: -0.63; P=0.005) and a trend for greater response with longer time post-transplant (P=0.052). 71 episodes of infection, predominantly respiratory viral, occurred in 23 subjects. Malignancy was observed in 5.

Conclusion: In this largest series to date, AL was associated with a significant decline in ΔFEV1 slope in lung transplant recipients with RP-CLAD. A larger response was observed in those with more rapid decline in FEV1. Additional studies of AL in CLAD are warranted.

Volume

45

Issue

5 Suppl

First Page

531

Comments

Richard DeVos Heart and Lung Transplant Program

Last Page

531

DOI

10.1016/j.healun.2026.02.1157

ISSN

1053-2498

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