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Multicenter Study
. 2025 Mar;206(3):924-929.
doi: 10.1111/bjh.19976. Epub 2025 Jan 7.

Venetoclax therapy in chronic lymphocytic leukaemia patients relapsed after allogeneic haematopoietic stem cell transplantation

Francesca Perutelli  1 , Elia Boccellato  2 , Maria Chiara Montalbano  1 , Gioacchino Catania  3 , Marina Deodato  4 , Anna Maria Frustaci  4 , Idanna Innocenti  5 , Riccardo Moia  6 , Francesca Maria Quaglia  7 , Giulia Quaresmini  8 , Paolo Rivela  3 , Gianluca Gaidano  6 , Mauro Krampera  7 , Luca Laurenti  5   9 , Alessandro Rambaldi  8 , Benedetto Bruno  1 , Candida Vitale  1 , Marta Coscia  10   11
Affiliations
Multicenter Study

Venetoclax therapy in chronic lymphocytic leukaemia patients relapsed after allogeneic haematopoietic stem cell transplantation

Francesca Perutelli et al. Br J Haematol. 2025 Mar.

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains an option for young and fit chronic lymphocytic leukaemia (CLL) patients with high-risk disease features. However, allotransplanted patients are generally excluded from clinical trials, making data regarding the use of venetoclax after alloHSCT extremely rare. We report data from 7 CLL patients who received venetoclax after alloHSCT among 53 Italian centers. These patients underwent alloHSCT between 2006 and 2021 after failing chemoimmunotherapy (7/7), ibrutinib (5/7) and/or idelalisib (1/7). Of note, 3/7 patients had already received venetoclax-based therapy before alloHSCT. Post-allo HSCT venetoclax treatment resulted safe, with adverse events not different from what reported in clinical trials. Importantly, no meaningful impact on graft versus host disease (GvHD) course was observed: 4/7 patients with pre-existing chronic GvHD had no exacerbation after venetoclax start, and only one patient developed GvHD during venetoclax therapy, that was managed as per standard clinical practice. Concerning efficacy, 5/7 patients presented a clinical response to venetoclax, with two patients achieving an undetectable minimal residual disease. To our knowledge, this is the largest reported series of CLL patients treated with venetoclax after alloHSCT. In these heavily pretreated and high-risk patients, previous alloHSCT did not compromise the feasibility of venetoclax therapy, that lacked unexpected toxicities and did not exacerbate GvHD.

Keywords: chronic lymphocytic leukaemia; stem cell transplantation; venetoclax.

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Conflict of interest statement

E.B. received honoraria from Amgen and BeiGene. A.M.F. served on advisory boards for AbbVie, Janssen, BeiGene and AstraZeneca. R.M. served on advisory boards for BeiGene and AbbVie. G.G. took part in speaker's bureau for AstraZeneca, BeiGene, Hikma and Johnson & Johnson and served on advisory boards for Abbvie, AstraZeneca, BeiGene, Hikma, Incyte, Johnson & Johnson and Lilly. B.B. received honoraria from Amgen, Janssen, Novartis, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Jazz Pharmaceuticals, AstraZeneca and Incyte and served on advisory boards for Amgen and Jazz Pharmaceuticals. C.V. received consultancy fees from AbbVie and AstraZeneca. M.C. received consultancy fees from AbbVie, AstraZeneca, BeiGene and Janssen and research funding from AbbVie and Janssen. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Patients' clinical history. Patients' clinical history with timing of subsequent lines of therapy, including allogeneic haematopoietic stem cell transplantation and venetoclax treatment. ALZ, alemtuzumab; CAR‐T, chimeric antigen receptor T cells; CIT, chemoimmunotherapy; CT, chemotherapy; DLI, donor lymphocyte infusion; HSCT, allogeneic haematopoietic stem cell transplantation; Ibr, ibrutinib; Len, lenalidomide; Obi‐Ven, venetoclax plus obinutuzumab; R‐idela, rituximab plus idelalisib; RT, radiotherapy; RTX, rituximab; and Ven, venetoclax.
See this image and copyright information in PMC

References

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