TY - JOUR
T1 - Venetoclax with azacitidine or decitabine in blast-phase myeloproliferative neoplasm
T2 - A multicenter series of 32 consecutive cases
AU - Gangat, Naseema
AU - Guglielmelli, Paola
AU - Szuber, Natasha
AU - Begna, Kebede H.
AU - Patnaik, Mrinal M.
AU - Litzow, Mark R.
AU - Al-Kali, Aref
AU - Foran, James M.
AU - Palmer, Jeanne M.
AU - Alkhateeb, Hassan
AU - Elliott, Michelle A.
AU - Hanson, Curtis A.
AU - Pardanani, Animesh
AU - Mannelli, Francesco
AU - Vannucchi, Alessandro M.
AU - Tefferi, Ayalew
N1 - Publisher Copyright:
© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - Venetoclax (Ven) combined with a hypomethylating agent (HMA) has now emerged as an effective treatment regimen for acute myeloid leukemia, in both de novo and relapsed/refractory setting. The current multicenter study retrospectively examined Ven + HMA treatment outcome among 32 patients (median age 69 years; 59% males) with blast-phase myeloproliferative neoplasm (MPN-BP). Pre-leukemic phenotype included essential thrombocythemia (ET)/post-ET myelofibrosis (34%), polycythemia vera (PV)/post-PV myelofibrosis (38%) and primary myelofibrosis (28%). Twenty-nine study patients were fully annotated cytogenetically and molecularly (NGS): 69% harbored complex karyotype and/or mutations, including TP53 (41%), IDH1/2 (21%), ASXL1 (21%), N/KRAS (14%), SRSF2 (10%), EZH2 (10%) and U2AF1 (7%). All patients received Ven combined with either azacitidine (n = 12) or decitabine (n = 20); either up front (n = 23) or after failing another induction therapy (n = 9). Complete remission with (CR) or without (CRi) count recovery was achieved in 14 (44%) patients and was more likely to occur in the absence of pre-leukemic PV/post-PV myelofibrosis phenotype (p <.01), complex karyotype (p <.01) or K/NRAS (p =.03) mutations; seven of eight patients (88%) without vs four of 21 (19%) with complex karyotype or K/NRAS mutation achieved CR/CRi (p <.01); all 11 informative patients with pre-leukemic PV/post-PV myelofibrosis phenotype displayed complex karyotype (p <.01). In contrast, neither TP53 (p =.45) nor IDH1/2 (p =.63) mutations affected response. Compared to historical controls treated with HMA alone (n = 26), the CR/CRi rate (44% vs 4%) and median survival (8 vs 5.5 months) were more favorable with Ven + HMA, but without significant difference in overall survival. Importantly, six patients with CR/CRi subsequently received allogeneic hematopoietic stem cell transplant (AHSCT). Note, Ven + HMA produces robust CR/CRi rates in MPN-BP, especially in the absence of RAS mutations and complex karyotype, thus enabling AHSCT, in some patients.
AB - Venetoclax (Ven) combined with a hypomethylating agent (HMA) has now emerged as an effective treatment regimen for acute myeloid leukemia, in both de novo and relapsed/refractory setting. The current multicenter study retrospectively examined Ven + HMA treatment outcome among 32 patients (median age 69 years; 59% males) with blast-phase myeloproliferative neoplasm (MPN-BP). Pre-leukemic phenotype included essential thrombocythemia (ET)/post-ET myelofibrosis (34%), polycythemia vera (PV)/post-PV myelofibrosis (38%) and primary myelofibrosis (28%). Twenty-nine study patients were fully annotated cytogenetically and molecularly (NGS): 69% harbored complex karyotype and/or mutations, including TP53 (41%), IDH1/2 (21%), ASXL1 (21%), N/KRAS (14%), SRSF2 (10%), EZH2 (10%) and U2AF1 (7%). All patients received Ven combined with either azacitidine (n = 12) or decitabine (n = 20); either up front (n = 23) or after failing another induction therapy (n = 9). Complete remission with (CR) or without (CRi) count recovery was achieved in 14 (44%) patients and was more likely to occur in the absence of pre-leukemic PV/post-PV myelofibrosis phenotype (p <.01), complex karyotype (p <.01) or K/NRAS (p =.03) mutations; seven of eight patients (88%) without vs four of 21 (19%) with complex karyotype or K/NRAS mutation achieved CR/CRi (p <.01); all 11 informative patients with pre-leukemic PV/post-PV myelofibrosis phenotype displayed complex karyotype (p <.01). In contrast, neither TP53 (p =.45) nor IDH1/2 (p =.63) mutations affected response. Compared to historical controls treated with HMA alone (n = 26), the CR/CRi rate (44% vs 4%) and median survival (8 vs 5.5 months) were more favorable with Ven + HMA, but without significant difference in overall survival. Importantly, six patients with CR/CRi subsequently received allogeneic hematopoietic stem cell transplant (AHSCT). Note, Ven + HMA produces robust CR/CRi rates in MPN-BP, especially in the absence of RAS mutations and complex karyotype, thus enabling AHSCT, in some patients.
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U2 - 10.1002/ajh.26186
DO - 10.1002/ajh.26186
M3 - Article
C2 - 33844862
AN - SCOPUS:85104873310
SN - 0361-8609
VL - 96
SP - 781
EP - 789
JO - American journal of hematology
JF - American journal of hematology
IS - 7
ER -