TY - JOUR
T1 - Safety and efficacy of durvalumab with R-CHOP or R2-CHOP in untreated, high-risk DLBCL
T2 - a phase 2, open-label trial
AU - Nowakowski, Grzegorz S.
AU - Willenbacher, Wolfgang
AU - Greil, Richard
AU - Larsen, Thomas S.
AU - Patel, Krish
AU - Jäger, Ulrich
AU - Manges, Robert F.
AU - Trümper, Lorenz
AU - Everaus, Hele
AU - Kalakonda, Nagesh
AU - Brown, Peter
AU - Jørgensen, Judit Meszaros
AU - Cunningham, David
AU - Dell’Aringa, Justine
AU - Fox, Brian
AU - Rubio, Neus Domper
AU - Kilavuz, Nurgul
AU - Casadebaig, Marie Laure
AU - Manzke, Oliver
AU - Munoz, Javier
N1 - Publisher Copyright:
© 2021, Japanese Society of Hematology.
PY - 2022/2
Y1 - 2022/2
N2 - Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have poor outcomes following first-line cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). Evidence shows chemotherapy and immune checkpoint blockade can increase antitumor efficacy. This study investigated durvalumab, a programmed death-ligand 1 inhibitor, combined with R-CHOP or lenalidomide + R-CHOP (R2-CHOP) in newly diagnosed high-risk DLBCL. Patients received durvalumab 1125 mg every 21 days for 2–8 cycles + R-CHOP (non-activated B-cell [ABC] subtype) or R2-CHOP (ABC), then durvalumab consolidation (1500 mg every 28 days). Of 46 patients, 43 received R-CHOP and three R2-CHOP. All patients had the high-risk disease; 14 (30.4%) and eight (17.4%) had double- or triple-hit DLBCL, respectively. Following induction, 20/37 (54.1%) patients receiving durvalumab + R-CHOP achieved complete response (CR), and seven (18.9%) partial response (PR); 25 (67.6% [95% CI 50.2–82.0]) continued to consolidation and were progression-free at 12 months. Among efficacy-evaluable patients with double- or triple-hit DLBCL (n = 12), five achieved CR and five PR. Adverse events were generally consistent with R-CHOP. Correlative analyses did not identify conclusive biomarkers of response. Durvalumab + R-CHOP is feasible in DLBCL with no new safety signals, but the combination provided no greater benefit than R-CHOP.
AB - Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have poor outcomes following first-line cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). Evidence shows chemotherapy and immune checkpoint blockade can increase antitumor efficacy. This study investigated durvalumab, a programmed death-ligand 1 inhibitor, combined with R-CHOP or lenalidomide + R-CHOP (R2-CHOP) in newly diagnosed high-risk DLBCL. Patients received durvalumab 1125 mg every 21 days for 2–8 cycles + R-CHOP (non-activated B-cell [ABC] subtype) or R2-CHOP (ABC), then durvalumab consolidation (1500 mg every 28 days). Of 46 patients, 43 received R-CHOP and three R2-CHOP. All patients had the high-risk disease; 14 (30.4%) and eight (17.4%) had double- or triple-hit DLBCL, respectively. Following induction, 20/37 (54.1%) patients receiving durvalumab + R-CHOP achieved complete response (CR), and seven (18.9%) partial response (PR); 25 (67.6% [95% CI 50.2–82.0]) continued to consolidation and were progression-free at 12 months. Among efficacy-evaluable patients with double- or triple-hit DLBCL (n = 12), five achieved CR and five PR. Adverse events were generally consistent with R-CHOP. Correlative analyses did not identify conclusive biomarkers of response. Durvalumab + R-CHOP is feasible in DLBCL with no new safety signals, but the combination provided no greater benefit than R-CHOP.
KW - Diffuse large B-cell lymphoma
KW - Durvalumab
KW - High risk
KW - R-CHOP
UR - http://www.scopus.com/inward/record.url?scp=85119490206&partnerID=8YFLogxK
U2 - 10.1007/s12185-021-03241-4
DO - 10.1007/s12185-021-03241-4
M3 - Article
C2 - 34797531
AN - SCOPUS:85119490206
SN - 0925-5710
VL - 115
SP - 222
EP - 232
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 2
ER -