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

Rivalta B, Wolkewitz M, Kusters M, Uhlmann A, Guarnieri V, Abou-Chahla W, Adjaoud D, Aladjidi N, Armari-Alla C, Azarnoush S, Baris S, …, Maccari ME · 2026 · Journal of Allergy and Clinical Immunology · Atlas ID RIV2026

What this study shows

In a 95-patient ESID registry of Activated PI3Kδ Syndrome (APDS), rapamycin and the targeted PI3Kδ inhibitor leniolisib produced comparable overall response rates for lymphoproliferation (67% vs 64%), but treatment-limiting adverse events occurred only in the rapamycin-treated group; lymphoma cases were observed during follow-up in the cohort.

Abstract

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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.

Read the full abstract on PubMed →

At a glance

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Evidence type H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type3 - Human Observational
Model systemHuman (retrospective multicenter registry, n=95 APDS patients)
JournalJournal of Allergy and Clinical Immunology
Year2026
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1016/j.jaci.2026.09.014 · PMID 42805311

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Beatrice Rivalta first author · 1 study in the Atlas

    First author of a multicenter registry analysis comparing rapamycin and leniolisib in a rare immune disorder

  • Maria Elena Maccari last author · 1 study in the Atlas

    Senior author studying primary immunodeficiencies and their treatment

More: 107 other authors

No profile yet: Wolkewitz M, Kusters M, Uhlmann A, Guarnieri V, Abou-Chahla W, Adjaoud D, Aladjidi N, Armari-Alla C, Azarnoush S, Baris S, Barlogis V, Barzaghi F, Baumann U, Bloomfield M, Bodet D, Boutboul D, Boz V, Bozkurt S, Bucciol G, Cancrini C, Catherinot E, Cavazzana M, Cheminant M, Chinello M, Ciznar P, Conti F, Costagliola G, Dalm V, D'Aveni-Piney M, Ekwall O, Eren E, Eric Z, Farmaki E, Fasth A, Fieschi C, Fischer A, Fournier B, Galicier L, Ghosh S, Gkantaras A, Hatchuel Y, Hilfanova A, Hoenig M, Jeziorski E, Jolles S, Karakoc-Aydiner E, Kilic SS, Kiykim A, Körholz J, Le Guenno G, Licciardi F, Lodi L, Lougaris V, Lucena JM, Malphettes M, Marzollo A, Masmas TN, Meinhardt A, Merlin E, Meyts I, Milota T, Moratti M, Moussouni N, Neth O, Nunes-Gomes C, Ocak S, Olbrich P, Yücel EÖ, Özen A, Schmid JP, Palma P, Pellier-Landreau I, Perlat A, Picard C, Prader S, Ricci S, Riviere J, Santilli V, Sarrot-Reynauld F, Schleinitz N, Schrijvers R, Schulz A, Schuetz C, Sediva A, Semeraro M, Sharapova S, Sogkas G, Soomann M, Palacín PS, Suarez F, Tessarin G, Tommasini A, Trück J, van Aerde K, van Montfrans J, Vermont C, Wustrau K, Zharankova Y, Moshous D, Neven B, Seidel MG, Chandra A, Thalhammer J, Kracker S, Ehl S, Mahlaoui N, Elfeky R

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Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionRapamycin (off-label) and/or leniolisib (PI3Kdelta inhibitor)
TargetPI3Kdelta / mTOR
ModelHuman (retrospective registry, 95 APDS patients)
EffectBoth drugs were associated with similar response rates for lymphoproliferation (67% vs 64%); treatment-limiting adverse events occurred only with rapamycin.

Cite this paper

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Rivalta, B., Wolkewitz, M., Kusters, M., Uhlmann, A., Guarnieri, V., Abou-Chahla, W., Adjaoud, D., Aladjidi, N., Armari-Alla, C., Azarnoush, S., Baris, S., Barlogis, V., Barzaghi, F., Baumann, U., Bloomfield, M., Bodet, D., Boutboul, D., Boz, V., Bozkurt, S., Bucciol, G., Cancrini, C., Catherinot, E., Cavazzana, M., Cheminant, M., Chinello, M., Ciznar, P., Conti, F., Costagliola, G., Dalm, V., D'Aveni-Piney, M., Ekwall, O., Eren, E., Eric, Z., Farmaki, E., Fasth, A., Fieschi, C., Fischer, A., Fournier, B., Galicier, L., Ghosh, S., Gkantaras, A., Hatchuel, Y., Hilfanova, A., Hoenig, M., Jeziorski, E., Jolles, S., Karakoc-Aydiner, E., Kilic, S. S., Kiykim, A., Körholz, J., Le Guenno, G., Licciardi, F., Lodi, L., Lougaris, V., Lucena, J. M., Malphettes, M., Marzollo, A., Masmas, T. N., Meinhardt, A., Merlin, E., Meyts, I., Milota, T., Moratti, M., Moussouni, N., Neth, O., Nunes-Gomes, C., Ocak, S., Olbrich, P., Yücel EÖ, Özen, A., Schmid, J. P., Palma, P., Pellier-Landreau, I., Perlat, A., Picard, C., Prader, S., Ricci, S., Riviere, J., Santilli, V., Sarrot-Reynauld, F., Schleinitz, N., Schrijvers, R., Schulz, A., Schuetz, C., Sediva, A., Semeraro, M., Sharapova, S., Sogkas, G., Soomann, M., Palacín, P. S., Suarez, F., Tessarin, G., Tommasini, A., Trück, J., van Aerde, K., van Montfrans, J., Vermont, C., Wustrau, K., Zharankova, Y., Moshous, D., Neven, B., Seidel, M. G., Chandra, A., Thalhammer, J., Kracker, S., Ehl, S., Mahlaoui, N., Elfeky, R., & Maccari, M. E. (2026). Leniolisib and rapamycin in Activated PI3-Kinase-δ-syndrome: a retrospective ESID registry-based analysis. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2026.09.014

@article{RIV2026,
  author       = {Rivalta, B. and Wolkewitz, M. and Kusters, M. and Uhlmann, A. and Guarnieri, V. and Abou-Chahla, W. and Adjaoud, D. and Aladjidi, N. and Armari-Alla, C. and Azarnoush, S. and Baris, S. and Barlogis, V. and Barzaghi, F. and Baumann, U. and Bloomfield, M. and Bodet, D. and Boutboul, D. and Boz, V. and Bozkurt, S. and Bucciol, G. and Cancrini, C. and Catherinot, E. and Cavazzana, M. and Cheminant, M. and Chinello, M. and Ciznar, P. and Conti, F. and Costagliola, G. and Dalm, V. and D'Aveni-Piney, M. and Ekwall, O. and Eren, E. and Eric, Z. and Farmaki, E. and Fasth, A. and Fieschi, C. and Fischer, A. and Fournier, B. and Galicier, L. and Ghosh, S. and Gkantaras, A. and Hatchuel, Y. and Hilfanova, A. and Hoenig, M. and Jeziorski, E. and Jolles, S. and Karakoc-Aydiner, E. and Kilic, S. S. and Kiykim, A. and Körholz, J. and Le Guenno, G. and Licciardi, F. and Lodi, L. and Lougaris, V. and Lucena, J. M. and Malphettes, M. and Marzollo, A. and Masmas, T. N. and Meinhardt, A. and Merlin, E. and Meyts, I. and Milota, T. and Moratti, M. and Moussouni, N. and Neth, O. and Nunes-Gomes, C. and Ocak, S. and Olbrich, P. and Yücel EÖ and Özen, A. and Schmid, J. P. and Palma, P. and Pellier-Landreau, I. and Perlat, A. and Picard, C. and Prader, S. and Ricci, S. and Riviere, J. and Santilli, V. and Sarrot-Reynauld, F. and Schleinitz, N. and Schrijvers, R. and Schulz, A. and Schuetz, C. and Sediva, A. and Semeraro, M. and Sharapova, S. and Sogkas, G. and Soomann, M. and Palacín, P. S. and Suarez, F. and Tessarin, G. and Tommasini, A. and Trück, J. and van Aerde, K. and van Montfrans, J. and Vermont, C. and Wustrau, K. and Zharankova, Y. and Moshous, D. and Neven, B. and Seidel, M. G. and Chandra, A. and Thalhammer, J. and Kracker, S. and Ehl, S. and Mahlaoui, N. and Elfeky, R. and Maccari, M. E.},
  title        = {{Leniolisib and rapamycin in Activated PI3-Kinase-δ-syndrome: a retrospective ESID registry-based analysis}},
  journal      = {Journal of Allergy and Clinical Immunology},
  year         = {2026},
  doi          = {10.1016/j.jaci.2026.09.014},
  note         = {PMID: 42805311},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record RIV2026) [Data set]. https://mtor-atlas.org/study/RIV2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_RIV2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record RIV2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/RIV2026/},
  doi          = {10.5281/zenodo.22059963}
}
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