Leniolisib and rapamycin in Activated PI3-Kinase-δ-syndrome: a retrospective ESID registry-based analysis.

Authors

Beatrice Rivalta, Martin Wolkewitz, Maaike Kusters, Annette Uhlmann, Valentina Guarnieri, Wadih Abou-Chahla, Dalila Adjaoud, Nathalie Aladjidi, Corinne Armari-Alla, Saba Azarnoush, Safa Baris, Vincent Barlogis, Federica Barzaghi, Ulrich Baumann, Marketa Bloomfield, Damien Bodet, David Boutboul, Valentina Boz, Selcen Bozkurt, Giorgia Bucciol, Caterina Cancrini, Emilie Catherinot, Marina Cavazzana, Morgane Cheminant, Matteo Chinello, Peter Ciznar, Francesca Conti, Giorgio Costagliola, Virgil Dalm, Maud D'Aveni-Piney, Olov Ekwall, Efrem Eren, Zelimir Eric, Evangelia Farmaki, Anders Fasth, Claire Fieschi, Alain Fischer, Benjamin Fournier, Lionel Galicier, Sujal Ghosh, Antonios Gkantaras, Yves Hatchuel, Anna Hilfanova, Manfred Hoenig, Eric Jeziorski, Stephen Jolles, Elif Karakoc-Aydiner, Sara S Kilic, Ayca Kiykim, Julia Körholz, Guillaume Le Guenno, Francesco Licciardi, Lorenzo Lodi, Vassilios Lougaris, José Manuel Lucena, Marion Malphettes, Antonio Marzollo, Tania N Masmas, Andrea Meinhardt, Etienne Merlin, Isabelle Meyts, Tomas Milota, Mattia Moratti, Nabila Moussouni, Olaf Neth, Christopher Nunes-Gomes, Süheyla Ocak, Peter Olbrich, Esra Özek Yücel, Ahmet Özen, Jana Pachlopnik Schmid, Paolo Palma, Isabelle Pellier-Landreau, Antoinette Perlat, Capucine Picard, Seraina Prader, Silvia Ricci, Jacques Riviere, Veronica Santilli, Francoise Sarrot-Reynauld, Nicolas Schleinitz, Rik Schrijvers, Ansgar Schulz, Catharina Schuetz, Anna Sediva, Michaela Semeraro, Svetlana Sharapova, Georgios Sogkas, Maarja Soomann, Pere Soler Palacín, Felipe Suarez, Giulio Tessarin, Alberto Tommasini, Johannes Trück, Koen van Aerde, Joris van Montfrans, Clementien Vermont, Katharina Wustrau, Yulia Zharankova, Despina Moshous, Bénédicte Neven, Markus G Seidel, Anita Chandra, Julian Thalhammer, Sven Kracker, Stephan Ehl, Nizar Mahlaoui, Reem Elfeky, Maria Elena Maccari, ESID-APDS Registry Working Party

Published in

The Journal of allergy and clinical immunology. Sep 28, 2026. Epub Sep 28, 2026.

Abstract

Activated PI3K-delta syndrome (APDS) is a rare inborn error of immunity characterized by variable immune dysregulation, recurrent infections, and increased risk of malignancy. Clinical management is challenging. Rapamycin has been widely used off-label to control immune dysregulation, while the selective PI3Kδ inhibitor leniolisib has recently become available as a disease-specific targeted therapy. Real-world data on these treatment approaches remain limited.
To assess real-world treatment indications, clinical course, immunological changes, and tolerability in patients with APDS treated with rapamycin and leniolisib.
We performed a retrospective analysis of the ESID-APDS registry including 95 APDS patients treated with rapamycin (81) and/or leniolisib (28) through a Managed Access Program. Clinical manifestations, immunological parameters, and treatment-associated complications were assessed.
Lymphoproliferation was the predominant indication (81% and 52% respectively) for treatment initiation. Overall responses (complete or partial) were observed in 67% of rapamycin- and 64% of leniolisib-treated patients. Across other disease manifestations, responses were documented in 35% and 50% of patients. Leniolisib was initiated for recurrent infections in 3 patients, whereas recurrent infections were not a primary indication for rapamycin. Treatment interruption due to adverse events occurred only in the rapamycin group. Lymphoma cases were observed during follow-up.
In this real-world registry cohort, both rapamycin and leniolisib were associated with improvement of lymphoproliferation in APDS. Treatment-limiting adverse events were reported under rapamycin. Prospective long-term studies are needed to better define the role of these therapies and their long-term impact on disease outcome, including malignancy risk.
In a real-world APDS cohort, leniolisib and rapamycin reduced benign lymphoproliferation, with treatment-limiting adverse events reported only under rapamycin.

PMID:
42805311
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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