Photo Credit: luchschenF

The following is a summary of “Nintedanib for patients with lymphangioleiomyomatosis: a phase 2, open-label, single-arm study,” published in the December 2024 issue of Pulmonology by Harari et al. 

Lymphangioleiomyomatosis, a rare disease primarily affecting women, can be stabilized with sirolimus, although drug toxicity and resistance are concerns. Nintedanib, a multikinase inhibitor targeting PDGFR, is a potential therapeutic option due to its activity in lymphangioleiomyomatosis lesions.  

Researchers conducted a retrospective study to analyze the activity and safety of nintedanib in individuals with lymphangioleiomyomatosis.  

They performed the study at MultiMedica IRCCS, Milan, Italy, a national referral center for rare pulmonary diseases. Participants aged 18 years or older, with sporadic or tuberous sclerosis complex-associated lymphangioleiomyomatosis and progressive pulmonary function decline over the past year, despite treatment with sirolimus or being treatment naïve were included. Nintedanib 150 mg was administered orally twice daily, with a reduction to 100 mg twice daily if side effects or hepatotoxicity occurred for 12 months, followed by an additional 12 months without treatment. The primary endpoint was the change in FEV₁ slope (L) over 12 months.  

The results showed from October 14, 2016, to December 13, 2019, 35 female participants (mean age 50 years [SD 11]) were enrolled, with 30 eligible for nintedanib treatment. After 12 months, 22 patients completed treatment, and 19 also completed 12 months of follow-up. FEV₁ remained steady after 1 year (predicted mean difference 0.001 L [95% CI –0.063 to 0.066]; P =0.97). During the 12 months off treatment, FEV₁ showed a slight decline (predicted mean difference –0.076 L [95% CI –0.149 to –0.004]; P =0.040). The most common adverse events that occurred in patients were nausea in 15 (50%), diarrhea in 8 (26%), and abdominal pain in 2 (7%) with no serious adverse events during treatment.  

Investigators concluded the nintedanib did not improve lung function in patients with lymphangioleiomyomatosis, it was well-tolerated, suggesting its potential as a second-line therapy, warranting further investigation in comparison to sirolimus. 

Source: thelancet.com/journals/lanres/article/PIIS2213-2600(24)00217-0/abstract