1Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
2Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
3Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
6Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
7Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
8Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
9Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea
10Department of Internal Medicine, Dongsan Medical Center, Daegu, Korea
11Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
12Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea
13Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea
14Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
15Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
16Hematology-Oncology Clinic, National Cancer Center, Goyang, Korea
17Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
18Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
19Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
20Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
21Department of Internal Medicine, Chungbuk National University Hospital, Chungju, Korea
22Department of Internal Medicine, Dong-A University Medical Center, Busan, Korea
23Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
24Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, Korea
25Department of Hematology-Oncology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
26Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
27Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea
28Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
Copyright © 2023 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The protocol was reviewed and approved by the institutional review board of each participating center, and all patients provided written informed consent before treatment initiation; Gachon University Gil Medical Center: GCIRB2015-74, Gyeongsang National University Hospital: GNUH 2015-02-012, Dongsan Medical Center: DSMC 2015-03-015, Korea University Anam Hospital: ED15-024(AN15024-001), Kosin University Gospel Hospital: KUGH 2017-09-008, National Cancer Center: NCC 2015-0091, Dong-A University Medical Center: DMC 15-037, Pusan National University Hospital: H-1701-011-051, Samsung Medical Center: SMC 2014-07-181, Seoul National University Hospital: H-1504-119-667, Asan Medical Center: S2015-0302-0001, Soonchunhyang University Hospital: SCHUH 2015-05-007, Soonchunhyang University Bucheon Hospital: SCHBC 2015-07-008, Wonju Severance Christian Hospital: CR315002-002, Ajou University Hospital: AJIRB-MED-OBS-14-254, Yeungnam University Medical Center: YUMC 2015-03-016, Korea Cancer Center Hospital: K-1409-001-001, Ulsan University Hospital: UUH 2015-11-007, Inje University Sanggye Paik Hospital: SGPAIK 2015-06-002, Inje University Ilsan Paik Hospital: ISPAIK 2015-07-002, Inje University Busan Paik Hospital: BS 2015-0110, Jeonbuk National University Hospital: CUH 2015-02-034, Chonnam National University Hwasun Hospital: TMP-2015-023, Chung-Ang University Hospital: C2015048(1506), Chungnam National University Hospital: CNUH 2015-10-060, Chungbuk National University Hospital: CBNUH 2015-03-006, Hallym University Sacred Heart Hospital: HUH 2015-I043.
Author Contributions
Conceived and designed the analysis: Yi JH, Jeong SH, Kim SJ, Yoon DH, Koh Y, Kim JS.
Collected the data: Lee WS, Yang DH, Do YR, Kim MK, Yoo KH, Choi YS, Yun WJ, Park Y, Jo JC, Park BB, Kang HJ, Yun WJ, Kwon JH, Hong DS, Lee HS, Lee GW.
Contributed data or analysis tools: Eom HS, Kwak JY, Shin HJ, Yi SY, Oh SY, Kim HJ, Sohn BS, Won JH.
Performed the analysis: Yi JH, Suh C.
Wrote the paper: Yi JH, Kim WS.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Values are presented as number (%). Platinum-based regimens include ICE (ifosfamide, carboplatin, etoposide, and dexamethasone), DHAP (cytarabine, cisplatin, dexamethasone), GDP (gemcitabine, cisplatin, and dexamethasone) and ESHAP/Ox (etoposide, methyl-prednisone, cytarabine, cisplatin or oxaliplatin); Methotrexate-based regimens include IMVP16 (ifosfamide, methotrexate, etoposide, and prednisone), IVAM (ifosfamide, etoposide, cytarabine, and methotrexate), and high-dose methotrexate; bendamustine-based regimens include benda-mustine with or without rituximab; miscellaneous regimens included brentuximab-vedotin (n=1), CODOX-M/IVAC (n=1), HyperCVAD (n=2), ibrutinib (n=1), and tafasitamab (n=2). CR, complete response; PR, partial response.
No. (%) | Overall response rate (%) | Overall survival (95% CI, mo) | Overall survival rate (%) | |
---|---|---|---|---|
SCHOLAR-1 study [9] | 636 (100) | 26 | 6.3 (5.9–7.0) | 1-Year: 28, 2-Year: 20 |
Primary refractory | 178 (28.0) | 20 | 7.1 | |
Refractory to salvage treatment | 318 (50.0) | 26 | 6.1 | |
Relapse ≤ 12 mo post-ASCT | 140 (22.0) | 34 | 6.2 | |
REAL-TREND study [22] | 350 (100) | 30 | 5.9 (5.5–7.1) | 2-Year: 16 |
Primary refractory | 181 (51.7) | 39 | 5.9 (5.5–7.1) | |
Refractory to salvage treatment | 148 (42.3) | 18 | 5.9 (3.2-not reached) | |
Relapse ≤ 12 mo post-ASCT | 21 (6.0) | 24 | ||
The current study | 260 (100) | 26.4 | 7.5 (6.4–8.6) | 2-Year: 22.1 |
Primary refractory | 102 (39.2) | 27.5 | 7.5 (5.2–9.8) | |
Refractory to salvage treatment | 133 (51.2) | 19.5 | 7.6 (6.5–8.7) | |
Relapse ≤ 12 mo post-ASCT | 25 (9.6) | 28.0 | 7.0 (5.6–8.4) |
Baseline characteristics of the refractory cohort (n=260)
Characteristic | PROCESS cohort | GIRAFFE-B cohort | Total |
---|---|---|---|
Age (yr) | 59 (26–85) | 64 (22–85) | 63 (22–85) |
≤ 60 | 30 (52.6) | 87 (42.9) | 117 (45.0) |
> 60 | 27 (47.4) | 116 (57.1) | 143 (55.0) |
Sex | |||
Male | 42 (73.7) | 124 (61.1) | 166 (63.8) |
Female | 15 (26.3) | 79 (38.9) | 94 (56.2) |
ECOG performance scale | |||
0–1 | 45 (78.9) | 50 (24.6) | 95 (36.5) |
2–4 | 12 (21.1) | 153 (75.4) | 165 (63.5) |
Ann-Arbor stage | |||
I–II | 16 (28.1) | 51 (25.1) | 67 (25.8) |
III–IV | 41 (71.9) | 152 (74.9) | 193 (74.2) |
No. of extranodal involvement | |||
0–1 | 25 (43.9) | 96 (47.3) | 121 (46.5) |
2 or more | 32 (56.1) | 107 (52.7) | 139 (53.5) |
Serum LDH | |||
Within normal limit | 11 (19.3) | 55 (27.1) | 66 (25.4) |
Elevated | 46 (80.7) | 148 (72.9) | 194 (74.6) |
IPI risk group | |||
Low | 7 (12.3) | 34 (16.7) | 41 (15.8) |
Low-intermediate | 15 (26.3) | 51 (25.1) | 66 (25.4) |
High-intermediate | 29 (50.9) | 56 (27.6) | 85 (32.7) |
High | 6 (10.5) | 62 (30.5) | 68 (26.2) |
Bone marrow involvement | |||
Absent | 41 (71.9) | 166 (81.8) | 207 (79.6) |
Present | 16 (28.1) | 37 (18.2) | 53 (20.4) |
B symptoms | |||
Absent | 41 (71.9) | 156 (76.8) | 197 (75.8) |
Present | 16 (28.1) | 47 (23.2) | 63 (24.2) |
Cell-of-origin classification by Han’s criteria (n=204) | |||
GCB subtype | 13 (38.2) | 56 (32.9) | 69 (33.8) |
Non-GCB subtype | 21 (51.8) | 114 (67.1) | 135 (66.2) |
Refractory category | |||
Primary refractory | 31 (54.4) | 71 (35.0) | 102 (39.2) |
Refractory to salvage treatment | 23 (40.4) | 110 (54.2) | 133 (51.2) |
Relapse ≤ 12 mo post-ASCT | 3 (5.3) | 22 (10.8) | 25 (9.6) |
Values are presented as median (range) or number (%). ASCT, autologous stem cell transplantation; ECOG, Eastern Cooperative Oncology Group; GCB, germinal center B-cell; IPI, international prognostic index; LDH, lactate dehydrogenase.
Response to chemotherapy after refractory disease
PROCESS | GRAFFE-B | Pooled | |
---|---|---|---|
Evaluated patients | 50 | 181 | 231 |
CR | 7 (14.0) | 18 (9.9) | 25 (9.6) |
PR | 5 (10.0) | 31 (17.1) | 36 (13.8) |
Overall response | 12 (24.0) | 49 (27.1) | 61 (26.4) |
SD | 10 (20.0) | 24 (13.3) | 34 (14.7) |
PD | 28 (56.0) | 108 (59.7) | 136 (58.9) |
ORR by refractory category | |||
Primary refractory (n=102) | - | - | 28 (27.5) |
Refractory to salvage treatment (n=133) | - | - | 26 (19.5) |
Relapse ≤ 12 mo post-ASCT (n=25) | - | - | 7 (28.0) |
Values are presented as number (%). ASCT, autologous stem cell transplantation; CR, complete response; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Response according to salvage regimens
Total/Evaluable | CR | PR | |
---|---|---|---|
Platinum-based regimens | 202/179 | 17 (9.5) | 30 (16.8) |
Methotrexate-based regimens | 35/32 | 5 (15.6) | 5 (15.6) |
Bendamustine-rituximab | 16/14 | 1 (7.1) | 1 (7.1) |
Miscellaneous | 7/6 | 2 (33.3) | 0 |
With anti-CD20 monoclonal antibodies | 47/41 | 6 (14.6) | 5 (12.2) |
Without anti-CD20 monoclonal antibodies | 213/190 | 19 (10.0) | 31 (16.3) |
Values are presented as number (%). Platinum-based regimens include ICE (ifosfamide, carboplatin, etoposide, and dexamethasone), DHAP (cytarabine, cisplatin, dexamethasone), GDP (gemcitabine, cisplatin, and dexamethasone) and ESHAP/Ox (etoposide, methyl-prednisone, cytarabine, cisplatin or oxaliplatin); Methotrexate-based regimens include IMVP16 (ifosfamide, methotrexate, etoposide, and prednisone), IVAM (ifosfamide, etoposide, cytarabine, and methotrexate), and high-dose methotrexate; bendamustine-based regimens include benda-mustine with or without rituximab; miscellaneous regimens included brentuximab-vedotin (n=1), CODOX-M/IVAC (n=1), HyperCVAD (n=2), ibrutinib (n=1), and tafasitamab (n=2). CR, complete response; PR, partial response.
Outcomes of patients with refractory DLBCL who met the criteria of the SCHOLAR-1 study
No. (%) | Overall response rate (%) | Overall survival (95% CI, mo) | Overall survival rate (%) | |
---|---|---|---|---|
SCHOLAR-1 study [ |
636 (100) | 26 | 6.3 (5.9–7.0) | 1-Year: 28, 2-Year: 20 |
Primary refractory | 178 (28.0) | 20 | 7.1 | |
Refractory to salvage treatment | 318 (50.0) | 26 | 6.1 | |
Relapse ≤ 12 mo post-ASCT | 140 (22.0) | 34 | 6.2 | |
REAL-TREND study [22] | 350 (100) | 30 | 5.9 (5.5–7.1) | 2-Year: 16 |
Primary refractory | 181 (51.7) | 39 | 5.9 (5.5–7.1) | |
Refractory to salvage treatment | 148 (42.3) | 18 | 5.9 (3.2-not reached) | |
Relapse ≤ 12 mo post-ASCT | 21 (6.0) | 24 | ||
The current study | 260 (100) | 26.4 | 7.5 (6.4–8.6) | 2-Year: 22.1 |
Primary refractory | 102 (39.2) | 27.5 | 7.5 (5.2–9.8) | |
Refractory to salvage treatment | 133 (51.2) | 19.5 | 7.6 (6.5–8.7) | |
Relapse ≤ 12 mo post-ASCT | 25 (9.6) | 28.0 | 7.0 (5.6–8.4) |
ASCT, autologous stem cell transplantation; CI, confidence interval; DLBCL, diffuse large B-cell lymphoma.
Values are presented as median (range) or number (%). ASCT, autologous stem cell transplantation; ECOG, Eastern Cooperative Oncology Group; GCB, germinal center B-cell; IPI, international prognostic index; LDH, lactate dehydrogenase.
Values are presented as number (%). ASCT, autologous stem cell transplantation; CR, complete response; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Values are presented as number (%). Platinum-based regimens include ICE (ifosfamide, carboplatin, etoposide, and dexamethasone), DHAP (cytarabine, cisplatin, dexamethasone), GDP (gemcitabine, cisplatin, and dexamethasone) and ESHAP/Ox (etoposide, methyl-prednisone, cytarabine, cisplatin or oxaliplatin); Methotrexate-based regimens include IMVP16 (ifosfamide, methotrexate, etoposide, and prednisone), IVAM (ifosfamide, etoposide, cytarabine, and methotrexate), and high-dose methotrexate; bendamustine-based regimens include benda-mustine with or without rituximab; miscellaneous regimens included brentuximab-vedotin (n=1), CODOX-M/IVAC (n=1), HyperCVAD (n=2), ibrutinib (n=1), and tafasitamab (n=2). CR, complete response; PR, partial response.
ASCT, autologous stem cell transplantation; CI, confidence interval; DLBCL, diffuse large B-cell lymphoma.