Rituximab-Lenalidomide-Ibrutinib Combination for Relapsed/Refractory Primary CNS Lymphoma: A Case Series of the LOC Network.

Caroline Houillier, Cecile Moluçon Chabrot, Marie-Pierre Moles-Moreau, Lise Willems, Guido Ahle, Agathe Waultier-Rascalou, Luc-Matthieu Fornecker, Khê Hoang-Xuan, Carole Soussain
Author Information
  1. Caroline Houillier: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris. caroline.houillier@aphp.fr.
  2. Cecile Moluçon Chabrot: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.
  3. Marie-Pierre Moles-Moreau: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.
  4. Lise Willems: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.
  5. Guido Ahle: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris. ORCID
  6. Agathe Waultier-Rascalou: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.
  7. Luc-Matthieu Fornecker: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.
  8. Khê Hoang-Xuan: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.
  9. Carole Soussain: From the APHP (C.H., K.H.-X.), Sorbonne Université, IHU, ICM, Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris; Service d'Hématologie (C.M.C.), CHU de Clermont-Ferrand, Clermont-Ferrand; Service des Maladies du Sang (M.-P.M.-M.), CHU d'Angers; APHP (L.W.), Hôpital Cochin, Service d'Hématologie, Paris; Service de Neurologie (G.A.), Hôpitaux Civils, Colmar; Service d'Hématologie (A.W.-R.), CHU de Nîmes; Service d'Hématologie (L.-M.F.), Institut de Cancérologie de Strasbourg Europe, Strasbourg; Service d'Hématologie (C.S.), Institut Curie, Site Saint Cloud; INSERM U932 (C.S.), Institut Curie, PSL Research University, Paris.

Abstract

BACKGROUND AND OBJECTIVES: To evaluate the efficacy and tolerance of the association rituximab-Lenalidomide-ibrutinib (RI) in relapsed/refractory (R/R) primary CNS lymphoma (PCNSL).
METHODS: R/R PCNSL patients treated with RI were retrospectively selected and analyzed from the French LOC database.
RESULTS: Fourteen patients (median age: 63 years, median Karnofsky Performance Status: 75%) received RI, administered after a median of 2 previous lines of chemotherapy, including autologous stem cell transplantation (ASCT) in 5 cases. The best response was complete response in 4/14 patients and partial response in 4/14 patients, achieved in a median of 2.5 months. Three responder patients received consolidation treatment (WBRT: N = 2, ASCT: N = 1) after RI, and RI served as a bridge before CAR-T cell therapy for one patient. RI was discontinued due to toxicity in 3/14 patients. There were no toxicity-related deaths.
DISCUSSION: The RI combination resulted in a high rate of response of rapid-onset in heavily pretreated patients with poor prognosis, with manageable toxicity, and allowed 3 patients to proceed to consolidation. Although preliminary, these results support the use of RI for R/R PCNSL failing conventional chemotherapies.
CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that combination of rituximab-Lenalidomide-ibrutinib induces a high rate of response in heavily pretreated R/R PCNSL.

MeSH Term

Adenine
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Central Nervous System Neoplasms
Female
Humans
Lenalidomide
Lymphoma, Large B-Cell, Diffuse
Male
Middle Aged
Neoplasm Recurrence, Local
Piperidines
Retrospective Studies
Rituximab

Chemicals

Piperidines
ibrutinib
Rituximab
Lenalidomide
Adenine

Word Cloud

Created with Highcharts 10.0.0RIpatientsresponseR/RPCNSLmedian2rituximab-lenalidomide-ibrutinibCNSLOCreceivedcell54/14consolidationN=toxicitycombinationhighrateheavilypretreatedBACKGROUNDANDOBJECTIVES:evaluateefficacytoleranceassociationrelapsed/refractoryprimarylymphomaMETHODS:treatedretrospectivelyselectedanalyzedFrenchdatabaseRESULTS:Fourteenage:63yearsKarnofskyPerformanceStatus:75%administeredpreviouslineschemotherapyincludingautologousstemtransplantationASCTcasesbestcompletepartialachievedmonthsThreerespondertreatmentWBRT:ASCT:1servedbridgeCAR-Ttherapyonepatientdiscontinueddue3/14toxicity-relateddeathsDISCUSSION:resultedrapid-onsetpoorprognosismanageableallowed3proceedAlthoughpreliminaryresultssupportusefailingconventionalchemotherapiesCLASSIFICATIONOFEVIDENCE:studyprovidesClassIVevidenceinducesRituximab-Lenalidomide-IbrutinibCombinationRelapsed/RefractoryPrimaryLymphoma:CaseSeriesNetwork

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