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An official publication of the Middle-Eastern Association for Cancer Research
Clinical Cancer Investigation Journal
ISSN Print: 2278-1668, Online: 2278-0513
ARTICLE
Year: 2022   |   Volume: 11   |   Issue: 3   |   Page: 15-20     View issue

Gemcitabine, Dexamethasone, Cisplatin with Rituximab in Treatment Transplant- Ineligible Relapsed Non-Hodgkin B-cell Lymphoma Patients

Tuan Tung Nguyen1, Van Hung Nguyen1, Minh Phuong Vu1,2*

1Center of Hematology and Blood Transfusion, Bach Mai Hospital, Hanoi, Vietnam. 2Department of Hematology, Hanoi Medical University, Hanoi, Vietnam.


Abstract

We conducted this study to find out the effectiveness of treatment as well as some prognostic factors when using R-GDP (Rituximab- Gemcitabine, Dexamethasone, and Cisplatin) regimen to treat transplant-ineligible relapsed non-Hodgkin B-cell lymphoma patients. 49 patients diagnosed with relapsed non-Hodgkin B-cell lymphoma treated with R-GDP (Rituximab- Gemcitabine, Dexamethasone, and Cisplatin) regimen were retrospectively analyzed. Patients who subsequently underwent autologous stem cell transplantation were excluded. After 2 cycles, ORR was 71.4%: CR: 12 patients (24.5%), PR: 23 patients (46.9%). 14 patients (28.6%) who did not achieve at least PR would be treated with another regimen. After 6 cycles, CR was 38.8% (19 patients). Median OS and PFS were 36 and 32 months; respectively. The 5-year rates were 36.4 % and 18.1% for OS and PFS; respectively. No serious side effects were reported. Neutrophilia and thrombocytopenia were grade 3, and grade 2; respectively. Univariate and multivariate analysis showed that LDH ≥237 U/L was an independent adverse prognostic factor for OS (P=0.003, HR: 6.256, 95% CI: 1.900- 20.602), BCL6 positive and LDH ≥ 237 U/L were an independent adverse prognostic factors for PFS (P=0.047, HR: 3.651, 95% CI: 1.020- 13.074; P=0.049; HR: 3.707, 95% CI: 1.004- 13.678; respectively). R-GDP is effective and has less toxicity in the treatment of transplant-ineligible relapsed non-Hodgkin B cell lymphoma patients, LDH ≥237 U/L is an independent adverse prognostic factor for OS and PFS, while BCL6 positive are independent adverse prognostic factors for PFS.

Keywords: Relapsed lymphoma, Non-Hodgkin B cell lymphoma, Gemcitabine, R-GDP, Transplant-ineligible


Introduction

Relapsed non-Hodgkin lymphoma treatment remains challenging.[1, 2] The most recognized standard regimen for the treatment of relapsed lymphoma is stem cell transplantation after high-dose chemotherapy such as ICE (ifosphamid, carboplatin, and etoposide), DHAP (dexamethasone, high-dose cytarabine, and cisplatin), ESHAP (etoposide, methylprednisolon, cytarabine, and cisplatin), in combination with rituximab if the patient has positive CD20.[3, 4] These regimens have a relatively high response rate but have limitations due to high toxicity, especially with high-dose cytarabine-containing regimens.[3-6] In general, it is probably only suitable for patients who have subsequently received an autologous stem cell transplant. For patients who are not eligible for stem cell transplantation, treatment after relapse is quite difficult. There is some research focusing on new active agents such as new antibodies, selinexor, ADC (antibody-drug conjugates), or CAR T cells.[7-9] Some clinical studies have shown that combinations of novel antibodies as atezolizumab with obinutuzumab, or a combination of new antibodies with targeted drugs as obinutuzumab with ibrutinib, or alone as blitunamumab, are also effective.[10-12] However, they are quite difficult to apply in developing countries due to the high cost.  Other studies seek directions in the combination of available drugs. Gemcitabine is one of those directions. Gemcitabine has excellent antitumor activity against a wide spectrum of solid human tumors.[13] Gemcitabine alone or in combination, and how to get the most effectiveness is a question that requires more research to answer. Ahn et al. suggested that gemcitabine alone was effective even in relapsed/refractory T/NK lymphoma.[14] According to several randomized trials, no salvage regimen was superior, in comparison with R-GDP (rituximab plus gemcitabine, dexamethasone, and cisplatin). Mi et al. compared the efficacy and toxicity of GDP

 

with ICE and showed that they were equivalent in efficiency.[15] Crump et al., and Hafez et al. showed that the patients with relapsed/refractory lymphoma treated with GDP had non-inferior survival, less toxicity, and better quality of life than those treated with DHAP.[16, 17] However, there is still controversy. Zlonick et al. showed the limited effectiveness of gemcitabine in the treatment of relapsed lymphoma.[18] Smith suggested that it is early to eliminate gemcitabine.[19] Gutierrez also agreed that there should be more gemcitabine-based regimens for non-Hodgkin lymphoma relapsed.[20]

Therefore, we conducted this study to find out the effectiveness of treatment as well as some prognostic factors when using an R-GDP regimen to treat transplant-ineligible relapsed non-Hodgkin B-cell lymphoma patients.

Materials and Methods

Patients

From March 2013 to September 2019, at the Center of Hematology and Blood Transfusion, in Bach Mai Hospital, Hanoi, Vietnam, 49 patients diagnosed with relapsed non-Hodgkin B-cell lymphoma treated with the R-GDP (Rituximab- Gemcitabine, Dexamethasone, and Cisplatin) regimen were retrospectively analyzed. The diagnosis was based on the HE stain and immunohistochemical stain with the marker: CD20, CD19, CD79a, CD3, CD5, CD23, CD10, MUM1, BCL6, and BCL2. Patients who subsequently underwent autologous stem cell transplantation were excluded.

Treatment

R-GDP consistent with gemcitabine (1,000 mg/m2) intravenous (IV) on days 1 and 8; cisplatin (75 mg/m2) IV on day 1; rituximab 375 mg/m2 IV on day 2; dexamethasone 40 mg IV on days 1-4; a cycle was administered every 3 weeks, for a total of six cycles. The response to chemotherapy was evaluated after 2 cycles; patients who did not achieve at least partial remission would be treated with another regimen.

Definition

The diagnosis was defined according to the WHO 2008 classification of hematopoietic and lymphoid tumors.[21] The stage was classified according to the Ann Arbor Stage. Response to chemotherapy was determined according to the criteria of the International Working Group (RECIL 2017).[22] Toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria.[23]

Statistics analysis

OS (Overall survival) was defined as the time from diagnosis of relapse to the last follow-up, or death. PFS (Progressing free survival) was defined as the time from the beginning of treatment to further progression of the disease, or death. The ROC curve (receiver operating characteristic) was used to separate for the LDH level to achieve a predictive value for OS and PFS. The cutoff value of the LDH level was 237 U/L. Univariate (using the Kaplan-Meyer method) and multivariate (using the Cox proportional hazards model) survival analyses were evaluated in OS and PFS for variables such as risk factors: age >65, time of relapse (≤12 months), type of lymphoma, non-GCB (non- germinal center B cell) type, BCL2 positive, BCL6 positive and LDH ≥237 U/L. P<0.05 was considered a significant statistical difference.

Results and Discussion

Patients characteristic

49 patients included 38 men (77.6%). The median age was 59 years (from 29 to 80). The laboratory indices and characteristics of the patients are shown in Tables 1 and 2. 61.2 % of the patients with a diagnosis of diffuse large B cell lymphoma (DLBCL) represent the highest percentage. In the group of patients with DLBCL, the non-GCB type was 20.4%, GCB type was 40.8%.

Table 1. Laboratory Indices of Patients

 

N

Minimum

Maximum

Mean

Std. Deviation

HGB (g/L)

49

69

160

117.00

21.495

WBC (x109 /L)

49

1.74

17.20

6.8994

2.98717

Platelet (x109 /L)

49

31

510

230.69

102.827

Ferritin (ng/mL)

49

8.40

4033.00

769.8735

781.93884

LDH (U/L)

49

118

1183

284.59

182.595

Ure (mmol/L)

49

2.80

22.10

6.2673

2.94593

Creatinin (mmol/L)

49

48

213

85.88

27.404

GOT (U/L)

49

2

99

33.06

18.873

GPT (U/L)

49

7

186

33.22

34.431

Valid N (listwise)

49

 

 

 

 

Treatment outcome

After 2 cycles, ORR (included CR and PR) was 71.4% with 35 patients:  CR: 12 patients (24.5%), PR: 23 patients (46.9%). 14 patients (28.6%) who did not achieve at least PR (included SD and relapse) would be treated with another regimen, (Table 3). After 6 cycles, the CR was 38.8% (19 patients), (Table 3). The median OS and PFS were 36 and 32 months, respectively (Table 4). The 5-year rates were 36.4 % and 18.1% for OS and PFS; respectively (Table 4).

Unvariate and multivariate analysis showed that LDH 237≥ U/L was an independent adverse prognostic factor for OS (P=0.003, HR: 6.256, 95% CI: 1.900- 20.602); BCL6 positive, and LDH ≥ 237 were independent adverse prognostic factors for PFS (P=0.047, HR: 3.651, 95% CI: 1.020- 13.074; P=0.049; HR: 3.707, 95% CI: 1.004- 13.678; respectively) (Table 5, Figures 1 and 2).

 

 

 

Table 2. Characteristics of Patients

 

Frequency

Percent

Valid Percent

Cumulative Percent

Sex

Male

38

77.6

77.6

77.6

Female

11

22.4

22.4

100.0

Total

49

100.0

100.0

 

Type

DLBCL

30

61.2

61.2

61.2

SLL

6

12.2

12.2

73.5

FL

2

4.1

4.1

77.6

Mantle cell lymphoma

6

12.2

12.2

89.8

Marginal zone lymphoma

2

4.1

4.1

93.9

MALT lymphoma

2

4.1

4.1

98.0

Lymphocyticplasmacytoid

1

2.0

2.0

100.0

Total

49

100.0

100.0

 

Time of relapse

≤12 months

5

10.2

10.2

10.2

>12 months

44

89.8

89.8

100.0

Total

49

100.0

100.0

 

B syndromes

No

14

28.6

28.6

28.6

Yes

35

71.4

71.4

100.0

Total

49

100.0

100.0

 

Lymphadenopathy

No

5

10.2

10.2

10.2

Yes

44

89.8

89.8

100.0

Total

49

100.0

100.0

 

Extranodal Involvement

No

27

55.1

55.1

55.1

Yes

22

44.9

44.9

100.0

Total

49

100.0

100.0

 

Hepatomegaly

No

42

85.7

85.7

85.7

Yes

7

14.3

14.3

100.0

Total

49

100.0

100.0

 

Splenomegaly

No

34

69.4

69.4

69.4

Yes

15

30.6

30.6

100.0

Total

49

100.0

100.0

 

Bone Marrow Involvement

No

34

69.4

69.4

69.4

Yes

15

30.6

30.6

100.0

Total

49

100.0

100.0

 

Ann Arbor Stage

II

4

8.2

8.2

8.2

III

6

12.2

12.2

20.4

IV

39

79.6

79.6

100.0

Total

49

100.0

100.0

 

GCB (germinal centre B-cell)

Yes

10

20.4

33.3

33.3

No

20

40.8

66.7

100.0

Total

30

61.2

100.0

 

Previous Protocol

R-CHOP

45

91.8

91.8

91.8

CHOP

3

6.1

6.1

98.0

COP

1

2.0

2.0

100.0

Total

49

100.0

100.0

 

Note: DLBCL: diffuse large B cell lymphoma, SLL: small lymphocytic lymphoma, FL: follicular lymphoma, MALT: mucosa-associated lymphoma tissue

Table 3. Response to chemotherapy

Cycles

Response Rate

Frequency

Percent

Valid Percent

Cumulative Percent

After 2 cycles

ORR

CR

12

24.5

24.5

24.5

PR

23

46.9

46.9

71.4

SD

7

14.3

14.3

85.7

Relapse

7

14.3

14.3

100.0

Total

49

100.0

100.0

 

After 6 cycles

ORR

CR

19

38.8

54.3

54.3

PR

16

32.7

45.7

100.0

Total

35

71.4

100.0

 

Note: ORR: overall response rate, CR: complete response, PR: partial response, SD: stable disease

 

Table 4. Overall survival (OS) and Progressing – free survival (PFS) follow in 5 years

Survival Time

Mean (95% Confidence Interval)

Median (95% Confidence Interval)

5 year rate

Estimate

Std. Error

Lower Bound

Upper Bound

Estimate

Std. Error

Lower Bound

Upper Bound

 

PFS (months)

32.761

3.728

25.453

40.069

32.000

6.835

18.603

45.397

18.1%

OS (months)

42.832

4.570

33.874

51.790

36.000

10.145

16.115

55.885

36.4%

 

Table 5. Prognostic factor for Overall survival (OS) and Progressing – free survival (PFS)

Factors

Univariate analysis (OS)

Multivariate analysis (OS)

P Log-rank value

HR

95%CI

P Cox value

Age >65 years

0.104

 

 

 

Time of relapse 12 months

0.113

 

 

 

Type of lymphoma

0.047

 

 

0.831

Non- GCB

0.675

 

 

 

Bcl2 positive

0.467

 

 

 

Bcl6 positive

0.057

 

 

 

LDH≥237 U/L

0.003

6.256

1.900- 20.602

0.003

Factors

Univariate analysis (PFS)

Multivariate analysis (PFS)

P Log-rank value

HR

95% CI

P Cox value

Age >65 years

0.606

 

 

 

Time of relapse 12 months

0.272

 

 

 

Type of lymphoma

0.082

 

 

 

Non- GCB

0.636

 

 

 

Bcl2 positive

0.233

 

 

 

Bcl6 positive

0.026

3.651

1.020- 13.074

0.047

LDH≥237 U/L

0.001

3.707

1.004- 13.678

0.049

 

 

Figure 1. OS (Overall survival) according to the LDH level (≥237 U/L vs <237 U/L)

 

 

Figure 2. PFS (Progressing free survival) according to the presence of BCL6 (positive vs negative)

 

Toxicity

No serious side effects were reported. Toxicity was mainly in the hematologic system. Neutropenia grades 1, 2, 3, and 4 were recorded in 16.2%, 10.3%, 38.8% and 24.5%; respectively. Thrombocytopenia grades 1, 2, and 3 were reported in 14.3%, 30.6%, 22.4%; respectively. No neurotoxicity was observed. No patient had to delay chemotherapy and no dose was reduced due to toxicity.

It is difficult to provide specific and uniform guidelines in the treatment of patients with relapsed cancer in general, as well as relapsed lymphoma in particular. The guidelines only offer several solutions to choose from. Even choosing a pretransplant regimen for eligible transplantation patients has been difficult, let alone ineligible transplantation patients.

Recent modern studies support the use of new drugs in patients with relapsed lymphoma who are ineligible for transplantation.[24-26] These studies show positive results but are difficult to apply in developing countries.

Gemcitabine is an analog of cytidine with a structure similar to cytarabine, but it has advantages over cytarabine.[13] Studies have shown that cytarabine needs to be replaced with gemcitabine to achieve efficiency and have yielded positive results.[15-17] Gemcitabine alone or in combination with other cytotoxic agents such as R-GDP (rituximab- gemcitabine, cisplatin, and dexamethasone) has a role in the treatment of relapsed lymphoma. Crump et al., Rybka et al., and Moccia et al. showed a gemcitabine-based regimen as R-GDP was effective and well tolerated in patients with relapsed/refractory lymphoma.[15, 27, 28] Therefore, an equally effective regimen with less toxicity than R-GDP may be appropriate for transplant-ineligible patients.

Hou et al. evaluated the efficacy of R-GDP in relapsed/ refractory aggressive B-cell Non-Hodgkin Lymphoma and showed after two cycles that ORR was 72.0%, 2-year OS and PFS were 70.0% and 48.0%, respectively.[29] Chiu et al. retrospectively analyzed transplant-ineligible patients treated with a gemcitabin-based regimen and showed ORR was 33%, EFS was 4.0 months, and OS was 18 months.[30] In our study, after 2 cycles, ORR was 71,4%, after 6 cycles, CR was 38.8%. On the other hand, the results for OS and PFS were positive. The median OS and median PFS were 32 months and 36 months; respectively. The 5-year rates were 36.4 % and 18.1% for OS and PFS; respectively.

Our study also showed that the R-GDP regimen has less toxicity. No serious advents were reported. Neutrophilia and thrombocytopenia were almost 3 or 2 grade. This result is similar to studies by Batgi et al., and Ghio et al.[31, 32]

We were also interested in prognostic factors. The prognosis of newly diagnosed lymphoma has been determined for each subtype. IPI (International Prognostic Index) for DLBCL, FILPI (Follicular Lymphoma International Prognostic Index) for FL (Follicular Lymphoma), and MIPI (Mantle Cell Lymphoma International Prognostic Index) for mantle cell lymphoma. However, for relapsed status, new prognostic factors must be evaluated. However, prognostic factors also change depending on the treatment regimen. For example, for FL, after the rituximab era, the prognostic system changed from FLIPI to FLIPI2.[33] Therefore, we try to understand some more prognostic factors in the group of patients treated with R-GDP. The results of the univariate and multivariate analysis showed that LDH 237 ≥ U/L is an adverse factor for both OS and PFS, while BCL6 is an adverse factor for PFS. We also tried to find out if the time of relapse ≤12 months and the types of lymphoma were significant, but so far no association was found.

Our study has some limitations. The number of patients is not much, the type of lymphoma is not homogeneous, nor can it be divided into groups to evaluate the difference because the number of each group is small.

Conclusion

R-GDP is effective and has less toxicity in the treatment of transplant-ineligible relapsed non-Hodgkin B cell lymphoma patients, LDH ≥237 U/L is an independent adverse prognostic factor for OS and PFS, while BCL6 positive are independent adverse prognostic factors for PFS.

Acknowledgments

The authors thank Prof. Quang Vinh Pham- Former Director of the Center of Hematology and Blood Transfusion for his efforts in supporting research.

Conflict of interest

None.

Financial support

None.

Ethics statement

The study protocol was approved by the Ethical Committee at Hanoi Medical University (no.187). Patient consent was waived by the committee as this study was a retrospective observational study.

References

1.        Nandagopal L, Mehta A. Treatment approaches of hard-to-treat non-Hodgkin lymphomas. Expert Rev Hematol. 2017;10(3):259-73. doi:10.1080/17474086.2017.1283214

2.        Goldfinger M, Cooper DL. Refractory DLBCL: Challenges and Treatment. Clin Lymphoma Myeloma Leuk. 2022;22(3):140-8. doi:10.1016/j.clml.2021.09.011

3.        Hashmi H, Hamadani M, Awan FT. Choosing the appropriate salvage therapy for B-cell non-Hodgkin lymphoma. Expert Opin Pharmacother. 2018;19(15):1631-4. doi:10.1080/14656566.2018.1518430

4.        Gopal AK, Press OW, Shustov AR, Petersdorf SH, Gooley TA, Daniels JT, et al. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010;51(8):1523-9. doi:10.3109/10428194.2010.491137

5.        Gisselbrecht C, Glass B, Mounier N, Gill DS, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-90. doi:10.1200/JCO.2010.28.1618

6.        Choi CW, Paek CW, Seo JH, Kim BS, Shin SW, Kim YH, et al. ESHAP salvage therapy for relapsed or refractory non-Hodgkin's lymphoma. J Korean Med Sci. 2002;17(5):621-4. doi:10.3346/jkms.2002.17.5.621

7.        Frontzek F, Karsten I, Schmitz N, Lenz G. Current options and future perspectives in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma. Ther Adv Hematol. 2022;13:20406207221103321. doi:10.1177/20406207221103321

8.        Moore DC, Peery MR, Tobon KA, Raheem F, Hwang GS, Alhennawi L, et al. New and emerging therapies for the treatment of relapsed/refractory diffuse large B-cell lymphoma. J Oncol Pharm Pract. 2022;10781552221096165. doi:10.1177/10781552221096165

9.        Wang L, Qin W, Huo YJ, Li X, Shi Q, Rasko JE, et al. Advances in targeted therapy for malignant lymphoma. Signal Transduct Target Ther. 2020;5(1):15. doi:10.1038/s41392-020-0113-2

10.      Palomba ML, Till BG, Park SI, Morschhauser F, Cartron G, Marks R, et al. Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B‐Cell Lymphoma: Results from a Phase 1b Study. Clin Lymphoma Myeloma Leuk. 2022;22(7):e443-51. doi:10.1016/j.clml.2021.12.010

11.      Kim MS, Banerjee T, Chen A, Danilov A, MacKinnon R, Thurlow B, et al. A phase II study of obinutuzumab in combination with ibrutinib for treatment of relapsed mantle cell lymphoma. Leuk Lymphoma. 2022:1-3. doi:10.1080/10428194.2022.2045598

12.      Coyle L, Morley NJ, Rambaldi A, Mason KD, Verhoef G, Furness CL, et al. Open-Label, phase 2 study of blinatumomab as second salvage therapy in adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Leuk Lymphoma. 2020;61(9):2103-12. doi:10.1080/10428194.2020.1759055

13.      Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E. Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016;78(1):1-2. doi:10.1007/s00280-016-3003-0

14.      Ahn HK, Kim SJ, Hwang DW, Ko YH, Tang T, Lim ST, et al. Gemcitabine alone and/or containing chemotherapy is efficient in refractory or relapsed NK/T-cell lymphoma. Invest New Drugs. 2013;31(2):469-72. doi:10.1007/s10637-012-9889-4

15.      Mi M, Zhang C, Liu Z, Wang Y, Li J, Zhang L. Gemcitabine, cisplatin, and dexamethasone and ifosfamide, carboplatin, and etoposide regimens have similar efficacy as salvage treatment for relapsed/refractory aggressive lymphoma: A retrospectively comparative study. Medicine. 2020;99(49):e23412. doi:10.1097/MD.0000000000023412

16.      Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32(31):3490-6. doi:10.1200/JCO.2013.53.9593

17.      Hafez R, Hussein S, Ismail M. Definitive salvage chemotherapy for the treatment of refractory/relapsed non-Hodgkin lymphoma, a single center experience. Alex J Med. 2018;54(4):679-83. doi:10.1016/j.ajme.2018.07.006

18.      Zlotnick M, Avigdor A, Ribakovsky E, Nagler A, Kedmi M. Efficacy of gemcitabine as salvage therapy for relapsed and refractory aggressive Non-Hodgkin lymphoma. Acta Haematol. 2019;141(2):84-90. doi:10.1159/000495283

19.      Smith SD. Gemcitabine: End of a Chemotherapy’s Era?. Acta Haematol. 2019;141(2):91-2. doi:10.1159/000496098

20.      Gutierrez A. Current real-life results and future options of gemcitabine-based salvage therapy for relapsed or refractory non-Hodgkin lymphoma. Acta Haematol. 2019;141(3):187-8. doi:10.1159/000496915

21.      Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019-32. doi:10.1182/blood-2011-01-293050

22.      Younes A, Hilden P, Coiffier B, Hagenbeek A, Salles G, Wilson W, et al. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol. 2017;28(7):1436-47. doi:10.1093/annonc/mdx097

23.      Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-65. doi:10.1200/JCO.2011.34.7625

24.      Thuresson PO, Vander Velde N, Gupta P, Talbot J. A systematic review of the clinical efficacy of treatments in relapsed or refractory diffuse large B cell lymphoma. Adv Ther. 2020;37(12):4877-93. doi:10.1007/s12325-020-01507-7

25.      Kasamon YL, Price LS, Okusanya OO, Richardson NC, Li RJ, Ma L, et al. FDA approval summary: selinexor for relapsed or refractory diffuse large B-cell lymphoma. Oncologist. 2021;26(10):879-86. doi:10.1002/onco.13859

26.      Davids MS, Roberts AW, Kenkre VP, Wierda WG, Kumar A, Kipps TJ, et al. Long-term follow-up of patients with relapsed or refractory non–hodgkin lymphoma treated with Venetoclax in a phase I, first-in-human study. Clin Cancer Res. 2021;27(17):4690-5.  doi:10.1158/1078-0432.CCR-20-4842

27.      Rybka J, Jurczak W, Giza A, Paszkiewicz-Kozik E, Kumiega B, Drozd-Sokołowska J, et al. Gemcitabine-based treatment in poor-prognosis patients with relapsed and refractory Hodgkin lymphoma and non-Hodgkin lymphoma: a multicenter Polish experience. Adv Clin Exp Med. 2015;24(5):783-9. doi:10.17219/acem/34795

28.      Moccia AA, Hitz F, Hoskins P, Klasa R, Power MM, Savage KJ, et al. Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma. Leuk Lymphoma. 2017;58(2):324-32. doi:10.1080/10428194.2016.1193852

29.      Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012;29(4):2409-16. doi:10.1007/s12032-012-0211-2

30.      Chiu M, Hague S, Elinder-Camburn A, Merriman E, Chan H. Retrospective Analysis of the Efficacy and Tolerability of Gemcitabine-Based Chemotherapy in Relapsed/Refractory Lymphoma Patients Not Eligible for Stem Cell Transplant. Clin Lymphoma Myeloma Leuk. 2022. doi:10.1016/j.clml.2022.06.010

31.      Batgi H, Merdin A, Dal MS, Kızıl Çakar M, Yıldız J, Başçı S, et. al. The effect of gemcitabine, dexamethasone, and cisplatin chemotherapy in relapsed/refractory NHL and HL patients: A single center experience. J Oncol Pharm Pract. 2020;26(8):1857-63. doi:10.1177/1078155220905654

32.      Ghio F, Cervetti G, Cecconi N, Pelosini M, Galimberti S, Morganti R, et al. Prognostic factors and efficacy of GDP-R therapy in refractory/relapsed diffuse large B-cell lymphomas not eligible for high-dose therapy. J Cancer Metastasis Treat. 2016;2:59-63. doi:10.4103/2394-4722.172291

33.      Liu Q, Silva A, Kridel R. Predicting early progression in follicular lymphoma. Ann Lymphoma. 2021;5(11).

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