Blood Res (2024) 59:36
Published online October 30, 2024
https://doi.org/10.1007/s44313-024-00042-6
© The Korean Society of Hematology
Correspondence to : *Correspondence:
Junning Cao
cao_junning@126.com
Fangfang Lv
lvff80@163.com
Guang‑Liang Chen
guangliang_chen@fudan.edu.cn
Full list of author information is available at the end of the article
†Youli Li, Yonghe Wu and Sufen Cao are equal contributors to this work and designated as co-first authors.
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Background Immunochemotherapy has demonstrated a promising efficacy for a variety of B-cell lymphoma but has limited efficacy for Epstein–Barr virus-positive (EBV +) diffuse large B-cell lymphoma (DLBCL) that is refractory or relapsed to conventional chemotherapy regimens. Considering higher programmed death-ligand 1 (PD-L1) expression in the subset of patients with DLBCL with positive EBV, we speculated that PD-1 inhibitors plus chemotherapy may be an alternative regimen in patients with refractory/relapsed EBV + DLBCL.
Methods This retrospective study included six adult patients diagnosed with refractory EBV + DLBCL resistant to first-line immunochemotherapy regimens (R-CHOP). These patients received PD-1 inhibitors plus chemotherapy as second-line treatment.
Results The final analysis included six patients (four men and two women (median age, 50 years; range, 39–83 years)). Four patients were diagnosed with Epstein–Barr virus (EBV) + DLBCL, and two had DLBCL associated with chronic inflammation. Over a median follow-up of 20 months (range, 2–31 months), the objective response rate was 83% (5/6) and the complete remission rate was 67% (4/6). No severe immune-related adverse reactions occurred, and only a mild rash was reported, which did not necessitate the discontinuation of therapy.
Conclusion The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treatment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.
Keywords Epstein–Barr virus, Diffuse large B-cell lymphoma, Chemotherapy, PD-1 inhibitors, Treatment resistance, Immunotherapy
Blood Res 2024; 59():
Published online October 30, 2024 https://doi.org/10.1007/s44313-024-00042-6
Copyright © The Korean Society of Hematology.
Youli Li1,3† , Yonghe Wu4†, Sufen Cao1,6†, Baohua Yu5, Qunling Zhang1,2, Zuguang Xia1,2, Junning Cao1,2*, Fangfang Lv1,2* and Guang‑Liang Chen1,2*
1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China. 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China. 3 Department of Medical Oncology, Fudan University Shanghai Cancer Center Xiamen Hospital, Xiamen 361026, P.R. China. 4 Department of Pathology, Fujian Province, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, P.R. China. 5 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China. 6 Present Address: Department of Nursing, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Correspondence to:*Correspondence:
Junning Cao
cao_junning@126.com
Fangfang Lv
lvff80@163.com
Guang‑Liang Chen
guangliang_chen@fudan.edu.cn
Full list of author information is available at the end of the article
†Youli Li, Yonghe Wu and Sufen Cao are equal contributors to this work and designated as co-first authors.
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Background Immunochemotherapy has demonstrated a promising efficacy for a variety of B-cell lymphoma but has limited efficacy for Epstein–Barr virus-positive (EBV +) diffuse large B-cell lymphoma (DLBCL) that is refractory or relapsed to conventional chemotherapy regimens. Considering higher programmed death-ligand 1 (PD-L1) expression in the subset of patients with DLBCL with positive EBV, we speculated that PD-1 inhibitors plus chemotherapy may be an alternative regimen in patients with refractory/relapsed EBV + DLBCL.
Methods This retrospective study included six adult patients diagnosed with refractory EBV + DLBCL resistant to first-line immunochemotherapy regimens (R-CHOP). These patients received PD-1 inhibitors plus chemotherapy as second-line treatment.
Results The final analysis included six patients (four men and two women (median age, 50 years; range, 39–83 years)). Four patients were diagnosed with Epstein–Barr virus (EBV) + DLBCL, and two had DLBCL associated with chronic inflammation. Over a median follow-up of 20 months (range, 2–31 months), the objective response rate was 83% (5/6) and the complete remission rate was 67% (4/6). No severe immune-related adverse reactions occurred, and only a mild rash was reported, which did not necessitate the discontinuation of therapy.
Conclusion The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treatment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.
Keywords: Epstein&ndash,Barr virus, Diffuse large B-cell lymphoma, Chemotherapy, PD-1 inhibitors, Treatment resistance, Immunotherapy
Table 1 . Baseline characteristics, first-line immunochemotherapy regimens and response of patients with refractory Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma.
Patient no | 1 | 2 | 3 | 4 | 5 | 6 |
---|---|---|---|---|---|---|
Age, years | 46 | 60 | 83 | 48 | 51 | 39 |
Sex | Male | Female | Male | Male | Male | Female |
Stage | II | III | IV | IV | IV | II |
ECOG PS | 1 | 1 | 1 | 3 | 2 | 1 |
Elevated LDH | No | Yes | Yes | Yes | Yes | Yes |
IPI score | 0 | 3 | 4 | 4 | 3 | 1 |
Bulky disease | Yes | No | No | No | No | Yes |
Cell of origin | NA | Non-GCB | Non-GCB | Non-GCB | Non-GCB | Non-GCB |
Immunochemotherapy(cycles) | R-CHOP (6) | R-CHOP (8) | R-miniCDOP (3) | R-miniCHOP (3) | R-CHOP (6) | R-CHOP(3), CHOP(2) |
Response | PR | PD | PD | PD | PD | PR |
ECOG PS Eastern Cooperative Oncology Group Performance Status, LDH lactate dehydrogenase, IPI International Prognostic Index, GCB germinal center B cell, NA not applicable, R-CHOP rituximab, cyclophosphamide, vindesine, doxorubicin, prednisone, PR partial response, PD progressive disease.
Table 2 . The outcomes of PD-1 inhibitors plus chemotherapy in patients with refractory EBV-positive diffuse large B-cell lymphoma.
Patient no | 1 | 2 | 3 | 4 | 5 | 6 |
---|---|---|---|---|---|---|
PD-1 inhibitors (cycles) | Tislelizumab (32) | Tislelizumab (5) | Sintilimab (8) | Sintilimab (16) | Sintilimab (18) | Camrelizumab (3) |
Combined chemotherapy regimens | R-CHOP × 2 | R-GP × 5 | G × 6 | R-ICE × 6 | P × 8; G × 6 | R-CHOP × 3 |
Response | CR | CR | CR | CR | PR | PD |
Final response | CR | CR | CR | CR | PD | PD |
PFS (months) | 19 + | 20 + | 22 + | 31 + | 10 | 2 |
OS (months) | 19 + | 20 + | 22 + | 31 + | 20 | 2 + |
irADRs (grade) | None | None | None | None | Skin rash (1) | None |
R-CHOP rituximab, cyclophosphamide, vindesine, doxorubicin, prednisone, R-GP rituximab, gemcitabine, cisplatinum, R-ICE rituximab, ifosfamide, carboplatin, and etoposide, G gemcitabine, P cisplatinum, CR complete response, PR partial response, PD progressive disease, OS Overall Survival, PFS progression-free survival, irADRs immune-related adverse drug reactions.
Shuku Sato, Shun Tsunoda, Wataru Kamata, Tomiteru Togano and Yotaro Tamai
Blood Res 2025; 60():Christian Omar Ramos Peñafiel, Daniela Pérez Sámano, Adán Germán Gallardo Rodríguez, Camila Terreros Palacio, Irma Olarte Carrillo, Carlos Martínez Murillo, Gilberto Barranco Lampón, Álvaro Cabrera García and Adolfo Martínez Tovar
Blood Res 2025; 60():Alireza Mohseni, Gholamreza Toogeh, Shahrbano Rostami, Mohammad Faranoush and Mohammad Jafar Sharifi
Blood Res 2024; 59():