TY - JOUR
T1 - Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD
AU - Thompson, Philip A.
AU - Keating, Michael J.
AU - Ferrajoli, Alessandra
AU - Jain, Nitin
AU - Peterson, Christine B.
AU - Garg, Naveen
AU - Wang, Sa A.
AU - Jorgensen, Jeffrey L.
AU - Kadia, Tapan M.
AU - Bose, Prithviraj
AU - Pemmaraju, Naveen
AU - Short, Nicholas J.
AU - Wierda, William G.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/7
Y1 - 2023/7
N2 - 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 β2-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.
AB - 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 β2-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.
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U2 - 10.1038/s41375-023-01901-4
DO - 10.1038/s41375-023-01901-4
M3 - Article
C2 - 37138019
AN - SCOPUS:85156193966
SN - 0887-6924
VL - 37
SP - 1444
EP - 1453
JO - Leukemia
JF - Leukemia
IS - 7
ER -