TY - JOUR
T1 - High-grade B-cell lymphoma, not otherwise specified
T2 - a multi-institutional retrospective study
AU - Zayac, Adam S.
AU - Landsburg, Daniel J.
AU - Hughes, Mitchell E.
AU - Bock, Allison M.
AU - Nowakowski, Grzegorz S.
AU - Ayers, Emily C.
AU - Girton, Mark
AU - Hu, Marie
AU - Beckman, Amy K.
AU - Li, Shaoying
AU - Medeiros, L. Jeffrey
AU - Chang, Julie E.
AU - Stepanovic, Adam
AU - Kurt, Habibe
AU - Sandoval-Sus, Jose
AU - Ansari-Lari, M. Ali
AU - Kothari, Shalin K.
AU - Kress, Anna
AU - Xu, Mina L.
AU - Torka, Pallawi
AU - Sundaram, Suchitra
AU - Smith, Stephen D.
AU - Naresh, Kikkeri N.
AU - Karimi, Yasmin H.
AU - Epperla, Narendranath
AU - Bond, David A.
AU - Farooq, Umar
AU - Saad, Mahak
AU - Evens, Andrew M.
AU - Pandya, Karan
AU - Naik, Seema G.
AU - Kamdar, Manali
AU - Haverkos, Bradley
AU - Karmali, Reem
AU - Oh, Timothy S.
AU - Vose, Julie M.
AU - Nutsch, Heather
AU - Rubinstein, Paul G.
AU - Chaudhry, Amina
AU - Olszewski, Adam J.
N1 - Publisher Copyright:
© 2023 by The American Society of Hematology.
PY - 2023
Y1 - 2023
N2 - In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)—a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.
AB - In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)—a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.
KW - A dual-expressor (MYC and BCL2) immunophenotype and TP53 alterations, but not MYC alterations, were significantly associated with worse PFS.
KW - HGBL-NOS is a highly heterogeneous category; PFS (55% at 2 years) did not significantly differ between R-CHOP and intensified regimens.
UR - http://www.scopus.com/inward/record.url?scp=85177207937&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85177207937&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2023009731
DO - 10.1182/bloodadvances.2023009731
M3 - Article
C2 - 37171397
AN - SCOPUS:85177207937
SN - 2473-9529
VL - 7
SP - 6381
EP - 6394
JO - Blood Advances
JF - Blood Advances
IS - 21
ER -