Safety And Efficacy Of Idelalisib Treatment Of Chronic Lymphocytic Leukemia (Cll) Or Lymphoma Relapsing After Allogeneic Hematopoietic Cell Transplantation (Allohct): A Survey By The Ebmt Chronic Malignancies And Lymphoma Working Parties

BACKGROUND: Idelalisib is a pathway inhibitor (PI) approved for the treatment of CLL and follicular lymphoma (FL). Idelalisib has a specific adverse effect profile including immune-mediated inflammatory conditions such as colitis and pneumonitis, raising concern about the safety of this PI if administered for treatment of malignancy recurrence after alloHCT. The purpose of this retrospective study was to provide information on the safety and efficacy of idelalisib in this setting. DESIGN: Eligible for this study were adult patients who had been registered with the EBMT for an alloHCT for CLL or lymphoma and who received idelalisib for treating disease relapse or persistence at any time after transplant as indicated by participating investigators upon request by the EBMT study office in Leiden. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were requested to provide additional treatment and follow-up information. RESULTS: As of June 22, 2017, a total of 28 patients had been registered, of whom an informative and plausible dataset as required for this analysis was available for 24 patients (CLL 17, FL 3, diffuse large B-cell lymphoma 3, peripheral T-cell lymphoma 1) who had undergone alloHCT between July 2009 and October 2015. All patients except three were male. Median age at transplantation was 54 (36-73) years. Prior to alloHCT, 6 patients (3 CLL and 3 lymphoma) had received an autoHCT and 2 other patients had been exposed to PI (idelalsib 1, ibrutinib 1). Disease status at alloHCT was sensitive in 63% of the patients. Conditioning was reduced-intensity in 67% of the transplants and included in-vivo T cell depletion in the majority of cases (79%). Donors were matched relatives in 50% with PBSC being the stem cell source in all cases. The interval between HCT and idelalisib commencement was 48 (0.5-79) months in the CLL group and 26 (1-69) months in the lymphoma group. Five patients with CLL had already failed ibrutinib given for post-HCT relapse prior to idelalisib. Prior to idelalisib, grade II-IV acute GVHD and chronic GVHD had been observed in 4% and 36% of the patients, but was still active at the time of idelalisib commencement in only 2 patients. After start of idelalisib, one patient developed grade 2 acute GVHD and subsequently chronic GVHD, however, in this patient idelalisib was started as early as 30 days after transplant. In none of the other patients de-novo GVHD or aggravation of pre-existing GVHD was reported. Best response on idelalisib in the CLL group was CR in one patient, stable disease in 3 patients, progression in 2 patients, and unavailable in the remainder. Eight patients with CLL underwent a subsequent treatment with an alternate PI (BTKi 5, 2 responses; venetoclax 3, no response). Considering documented idelalisib discontinuation, disease progression, retreatment, or death as events, the median event-free survival after start of idelalisib in the CLL group was 271 days, and the median OS 381 days. Altogether, there were 11 deaths, all due to disease progression (CLL 7, lymphoma 4). Median OS from start of idelalisib for all 24 patients was 362 days, with a median observation time of survivors of 9 (1-23) months. CONCLUSION: This study does not support concerns about the safety of idelalisib in the post alloHCT setting in patients with CLL and lymphoma. However, in this high-risk selection including ibrutinib-resistant patients, disease control under idelalisib was limited, implying that the role and timing of idelalisib for treatment of post-transplant CLL recurrence remains to be defined. Disclosures Dreger: Riemser: Consultancy, Research Funding; Jansen: Consultancy; medac: Other: Travel grants; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; medac: Other: Travel grants; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; medac: Other: Travel grants; medac: Other; medac: Other; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; medac: Other: Travel grants; medac: Other; Jansen: Consultancy; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Jansen: Consultancy; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding. Scheid: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Thieblemont: Celgene: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy; Abbvie: Consultancy, Honoraria; Cellectis: Speakers Bureau; Sanofi: Other: travel expenses. Gribben: Unum: Consultancy; Celgene: Consultancy; Janssen: Research Funding; Acerta: Research Funding; Gilead: Other: travel expenses. Corradini: Celgene: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Gilead: Honoraria. Kobbe: Celgene: Other: Advisory Board, Research Funding. Leblond: SERVIER: Honoraria, Membership on an entity9s Board of Directors or advisory committees; GILEAD: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; JANSSEN: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; ABBVIE: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; ROCHE: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Kroger: Neovii Pharmaceuticals AG: Speakers Bureau; Janssen Global Services, LLC: Speakers Bureau; Amgen Inc.: Speakers Bureau; Novartis AG: Research Funding; RIEMSER Pharma: Research Funding; Novartis AG: Speakers Bureau; Sanofi: Speakers Bureau. Schetelig: Sanofi Aventis: Consultancy, Research Funding; Roche: Honoraria; Abbvie: Honoraria; Janssen: Consultancy, Honoraria.