Venetoclax Yields Responses After alloHSCT in Small Relapsed CLL Cohort


The safety profile of venetoclax following allogeneic hematopoietic stem cell transplantation in patients with chronic lymphocytic leukemia appears to be comparable with other reports in clinical trials.

Venetoclax previously received FDA approval as a treatment for adult patients with CLL or small lymphocytic lymphoma in May 2019.

Venetoclax previously received FDA approval as a treatment for adult patients with CLL or small lymphocytic lymphoma in May 2019.

Prior allogeneic hematopoietic stem cell transplantation (alloHSCT) did not impact the ability of venetoclax (Venclexta) to produce objective responses among a small cohort of patients with heavily pretreated, high-risk chronic lymphocytic leukemia (CLL), according to findings from a multi-center study.1

Investigators reported a partial response (PR) with venetoclax therapy in 5 of 7 patients with CLL; of those with a PR, 2 achieved minimal residual disease negativity. Treatment duration with venetoclax lasted anywhere from 4 to 35 months. A sustained response occurred in 2 patients after receiving venetoclax for 2 years.

Investigators of this observational, multi-center, retrospective study evaluated the possibility of administering venetoclax to patients with CLL who had previously undergone alloHSCT. Data were gathered among 53 surveyed hematology centers in Italy, 35 of which responded.

Patients received venetoclax at 400 mg once a day apart from one who received 200 mg and another who was treated with 300 mg once a day. Most of the population received venetoclax alone; a single patient was treated with venetoclax in combination with obinutuzumab (Gazyva).

All patients with CLL were diagnosed between 2002 and 2016, and all received alloHSCT between 2006 and 2021. Investigators reported that all patients (n = 7/7) had disease progression following alloHSCT. Additionally, patients progressed following prior therapy with ibrutinib (Imbruvica; n = 5/7) and idelalisib (Zydelig; n = 1/7).

Most patients received a transplantation from a matched unrelated donor (n = 5/7) and were treated with a non-myeloablative conditioning combination (n = 5/7). Previous treatment with venetoclax was administered to 3 patients before alloHSCT.

Venetoclax following alloHSCT appeared to be safe, as toxicity was similar to those observed in other clinical trials. Adverse effects (AEs) included grade 3/4 neutropenia in 4 patients and grade 2 infection in 1. Among 4 patients with pre-existing graft-versus-host-disease (GVHD), treatment with venetoclax had no effect on these conditions, although a single patient developed GVHD while receiving study treatment. Two of 5 patients experienced an improvement in GVHD symptoms with venetoclax therapy; steroid therapy doses were decreased in 3 of 5 patients.

Investigators presented these findings in a poster at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting.

Venetoclax previously received FDA approval as a treatment for adult patients with CLL or small lymphocytic lymphoma in May 2019.2 Supporting data for the approval came from the phase 3 CLL4 trial (NCT02242942), in which investigators evaluated the efficacy and safety of venetoclax plus obinutuzumab compared with chlorambucil plus obinutuzumab in 432 patients who received no prior treatment for CLL.

Investigators of the CLL14 trial reported a statistically significant improvement in progression-free survival (PFS) among patients who received the venetoclax-based regimen (HR, 0.33; 95% CI, 0.22-0.51; P <.0001). After a median follow-up of 28 months, the median PFS was not reached in either treatment arm. Additionally, the objective response rate was 85% in patients receiving venetoclax compared with 71% of those who were treated with chlorambucil.

The most common AEs observed in the CLL14 trial included neutropenia, thrombocytopenia, anemia, diarrhea, nausea, cough, upper respiratory tract infection, musculoskeletal pain, fatigue, and edema.


  1. Perutelli F, Boccellato E, Catania G, et al. Venetoclax therapy in chronic lymphocytic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation. Presented at: 2023 Society of Hematologic Oncology (SOHO). Annual Meeting; September 6-9, 2023; Houston, TX; abstract CLL-347.
  2. FDA approves venetoclax for CLL and SLL. News release. FDA. May 15, 2019. Accessed December 4, 2023.
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