Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD.
Phillip A ThompsonMichael J KeatingAlessandra FerrajoliNitin JainChristine B PetersonNaveen GargSa A WangJeffrey L JorgensenTapan Mahendra KadiaPrithviraj BoseNaveen PemmarajuNicholas James ShortWilliam G WierdaPublished in: Leukemia (2023)
Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53 mutation and/or deletion, ATM deletion, complex karyotype or persistently elevated β 2 -microglobulin). The primary endpoint was U-MRD with 10 -4 sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were in MRD + CR at venetoclax initiation). U-MRD4 at 12mo was 57%. 32/45 (71%) had U-MRD at the completion of venetoclax: 22/32 stopped ibrutinib; 10 continued ibrutinib. At a median of 41 months from venetoclax initiation, 5/45 patients have progressed; none have died from CLL or Richter Transformation. In 32 patients with BM U-MRD4, peripheral blood (PB) MRD4 was analyzed every 6 months; 10/32 have had PB MRD re-emergence at a median of 13 months post-venetoclax. In summary, the addition of venetoclax in patients treated with ≥12mo of ibrutinib achieved high rate of BM U-MRD4 and may achieve durable treatment-free remission.
Keyphrases
- chronic lymphocytic leukemia
- end stage renal disease
- newly diagnosed
- bone marrow
- chronic kidney disease
- ejection fraction
- peripheral blood
- peritoneal dialysis
- stem cells
- dna damage
- machine learning
- heavy metals
- oxidative stress
- deep learning
- systemic lupus erythematosus
- rheumatoid arthritis
- risk assessment
- smoking cessation
- dna repair