TY - JOUR
T1 - Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure
AU - Ayers, Emily C.
AU - Li, Shaoying
AU - Medeiros, L. Jeffrey
AU - Bond, David A.
AU - Maddocks, Kami J.
AU - Torka, Pallawi
AU - Mier Hicks, Angel
AU - Curry, Madeira
AU - Wagner-Johnston, Nina D.
AU - Karmali, Reem
AU - Behdad, Amir
AU - Fakhri, Bita
AU - Kahl, Brad S.
AU - Churnetski, Michael C.
AU - Cohen, Jonathon B.
AU - Reddy, Nishitha M.
AU - Modi, Dipenkumar
AU - Ramchandren, Radhakrishnan
AU - Howlett, Christina
AU - Leslie, Lori A.
AU - Cytryn, Samuel
AU - Diefenbach, Catherine S.
AU - Faramand, Rawan
AU - Chavez, Julio C.
AU - Olszewski, Adam J.
AU - Liu, Yang
AU - Barta, Stefan K.
AU - Mukhija, Dhruvika
AU - Hill, Brian T.
AU - Ma, Helen
AU - Amengual, Jennifer E.
AU - Nathan, Sunita
AU - Assouline, Sarit E.
AU - Orellana-Noia, Victor M.
AU - Portell, Craig A.
AU - Chandar, Ashwin
AU - David, Kevin A.
AU - Giri, Anshu
AU - Hess, Brian T.
AU - Landsburg, Daniel J.
N1 - Funding Information:
Maki J. Maddocks reports personal fees from Pharmacyclics, Celgene, Teva, and Sandoz outside the submitted work. Nina D. Wagner‐Johnston reports personal fees from Bayer, Gilead, Juno, ADC Therapeutics, and Janssen Pharmaceuticals outside the submitted work. Bita Fakhri reports institutional research support from Bristol‐Myers Squibb and Takeda and personal fees from Gilead/Kite Pharmaceuticals, Juno/Kite Pharmaceuticals, and AstraZeneca outside the submitted work. Amir Behdad reports personal fees from Thermo Fisher Scientific, Bayer HealthCare Pharmaceuticals, and Pfizer Pharmaceuticals outside the submitted work. Jonathon B. Cohen reports grants from Takeda, Bristol‐Myers Squibb, Novartis, LAM Therapeutics (LAM), BioInvent, Genentech, Lympoma Research Fund (LRF), American Society of Hematology (ASH), Seattle Genetics, and AstraZeneca and personal fees from Seattle Genetics and Gilead outside the submitted work. Nishitha M. Reddy reports grants from Merck, grants and personal fees from Bristol‐Myers Squibb, and personal fees from Gilead, Celgene, AbbVie, and Genentech outside the submitted work. Lori A. Leslie reports personal fees from Celgene, Seattle Genetics, and Kite Pharmaceuticals outside the submitted work. Adam J. Olszewski reports institutional research funding from Spectrum Pharmaceuticals, Roche/Genentech, and TG Therapeutics outside the submitted work. Brian T. Hill reports grants and personal fees from Genentech during the conduct of the study. Stefan K. Barta reports grants from Celgene, Takeda, Merck, and Bayer; grants and personal fees from Seattle Genetics; and personal fees from Janssen Pharmaceutical and Mundipharma outside the submitted work. Sarit E. Assouline reports personal fees from Roche Canada, Pfizer, Janssen Pharmaceuticals, and AbbVie outside the submitted work. Craig A. Portell reports grants and personal fees from Kite Pharmaceuticals and Genentech outside the submitted work. Daniel J. Landsburg reports institutional research support from Triphase, Takeda, and Curis and personal fees from Curis outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2019 American Cancer Society
PY - 2020/1/15
Y1 - 2020/1/15
N2 - Background: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. Methods: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. Results: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P <.001) and OS (6 months vs not reached; P <.001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. Conclusions: Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.
AB - Background: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. Methods: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. Results: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P <.001) and OS (6 months vs not reached; P <.001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. Conclusions: Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.
KW - chemotherapy
KW - diffuse large B-cell lymphoma
KW - high-grade B-cell lymphoma
KW - relapsed/refractory
KW - salvage therapy
UR - http://www.scopus.com/inward/record.url?scp=85073980898&partnerID=8YFLogxK
U2 - 10.1002/cncr.32526
DO - 10.1002/cncr.32526
M3 - Article
C2 - 31568564
AN - SCOPUS:85073980898
SN - 0008-543X
VL - 126
SP - 293
EP - 303
JO - Cancer
JF - Cancer
IS - 2
ER -