Clinico-pathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax
- Author(s)
- Anderson, MA; Tam, C; Lew, TE; Juneja, S; Juneja, M; Westerman, D; Wall, M; Lade, S; Gorelik, A; Huang, DCS; Seymour, JF; Roberts, AW;
- Details
- Publication Year 2017,Volume 129,Issue #25,Page 3362-3370
- Journal Title
- Blood
- Publication Type
- Journal Article
- Abstract
- The BCL2 inhibitor venetoclax achieves responses in ~79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemo-immunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinico-pathological features of PD and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pre-treated patients on three early phase clinical trials. Investigations at progression included PET scan and biopsy. Twenty-five (37%) patients manifested PD on therapy: 17 with Richter transformation (RT) and eight with progressive CLL/SLL. RT occurred significantly earlier (median 7.9 months) than progressive CLL (median 23.4 months) (p = 0.003). Among patients who received the recommended phase II dose of venetoclax or higher (>/=400mg/day), fludarabine-refractoriness and complex karyotype were associated with progression (hazard ratio 7.01 (95%CI 1.7 - 28.5); p=0.002 and 6.6 [1.5 - 29.8]; p = 0.005, respectively); while del(17p) and/or TP53 mutation were not (p=0.75). Median post-progression survival was 13 (<1 - 49.9) months. BTK inhibitors were active in progressive CLL, but outcomes were mixed. Patients with disease that is fludarabine-refractory or has complex cytogenetics should have occult RT excluded before initiating venetoclax therapy.
- Research Division(s)
- Cancer And Haematology
- PubMed ID
- 28473407
- Publisher's Version
- https://doi.org/10.1182/blood-2017-01-763003
- NHMRC Grants
- NHMRC/1016647, NHMRC/1016701,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-05-30 09:30:46
Last Modified: 2018-05-04 02:08:57