Cancer Research and Treatment

Original Articles

Real-World Experience of Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Multiple Myeloma Relapsed/Refractory to Bortezomib and Lenalidomide: Cheongin Yang, Changgon Kim, Kunye Kwak, Ka-Won Kang, Yong Park, Byung Soo Kim, Seong Hyun Jeong, Joon Seong Park, Yoon Seok Choi; Received April 17, 2025 Accepted April 24, 2025 Published online April 25, 2025; DOI: https://doi.org/10.4143/crt.2025.418 [Accepted]

Abstract PDF: Purpose
This retrospective study evaluated the efficacy and safety of a weekly carfilzomib, cyclophosphamide, and dexamethasone (KCd) regimen in patients with relapsed or refractory multiple myeloma (RRMM) who had been previously treated with both bortezomib- and lenalidomide-containing regimens.
Materials and Methods
We conducted a retrospective analysis of 33 patients with RRMM who received the KCd regimen between March 2020 and February 2024. All patients had prior exposure to both bortezomib and lenalidomide, and the majority (93.9%) were refractory to lenalidomide. Carfilzomib was administered once weekly at 70 mg/m² (after a step-up dose), along with oral cyclophosphamide and dexamethasone. Treatment response was assessed according to the International Myeloma Working Group (IMWG) criteria, and survival outcomes were analyzed.
Results
The overall response rate was 66.7%, including a complete response or better in 15.1% of patients and a very good partial response or better in 42.4%. With a median follow-up of 31.7 months, the median progression-free survival (PFS) was 13.5 months (95% CI, 11.47–15.53), while the median overall survival (OS) was not reached. The most common grade ≥3 adverse event was neutropenia (15.2%). Non-hematologic grade ≥3 toxicities were infrequent and manageable.
Conclusion
The weekly KCd regimen demonstrated encouraging efficacy and tolerability in a heavily pretreated RRMM population. These findings support its use as a feasible treatment option, particularly in patients refractory to lenalidomide.

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Hematologic malignancy

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study: Yoon Seok Choi, Joonho Shim, Ka-Won Kang, Sang Eun Yoon, Jun Sik Hong, Sung Nam Lim, Ho-Young Yhim, Jung Hye Kwon, Gyeong-Won Lee, Deok-Hwan Yang, Sung Yong Oh, Ho-Jin Shin, Hyeon-Seok Eom, Dok Hyun Yoon, Hong Ghi Lee, Seong Hyun Jeong, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2025;57(1):267-279. Published online July 16, 2024; DOI: https://doi.org/10.4143/crt.2024.479

Abstract PDF Supplementary Material PubReader ePub: Purpose
This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea.
Materials and Methods
Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response.
Results
Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression.
Conclusion
This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

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Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts: Jun Ho Yi, Seong Hyun Jeong, Seok Jin Kim, Dok Hyun Yoon, Hye Jin Kang, Youngil Koh, Jin Seok Kim, Won-Sik Lee, Deok-Hwan Yang, Young Rok Do, Min Kyoung Kim, Kwai Han Yoo, Yoon Seok Choi, Whan Jung Yun, Yong Park, Jae-Cheol Jo, Hyeon-Seok Eom, Jae-Yong Kwak, Ho-Jin Shin, Byeong Bae Park, Seong Yoon Yi, Ji-Hyun Kwon, Sung Yong Oh, Hyo Jung Kim, Byeong Seok Sohn, Jong Ho Won, Dae-Sik Hong, Ho-Sup Lee, Gyeong-Won Lee, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2023;55(1):325-333. Published online April 22, 2022; DOI: https://doi.org/10.4143/crt.2022.008

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Purpose
Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal.
Materials and Methods
We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation.
Results
Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529).
Conclusion
In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Citations

Citations to this article as recorded by

PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial
Peng Sun, Hong Cen, Haiyan Yang, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu, Zhi-Ming Li
Cancer Cell International.2025;[Epub] CrossRef
Improving access to chimeric antigen receptor T-cells for refractory or relapsing diffuse large B cell lymphoma therapy in Asia
Ya Hwee Tan, Dok Hyun Yoon, Andrew J. Davies, Christian Buske, Yang Liang Boo, Nagavalli Somasundaram, Francesca Lim, Shin Yeu Ong, Anand Jeyasekharan, Koji Izutsu, Won Seog Kim, Jason Yongsheng Chan
Discover Oncology.2025;[Epub] CrossRef
Recent advances in cellular immunotherapy for lymphoid malignancies
Haerim Chung, Hyunsoo Cho
Blood Research.2023; 58(4): 166. CrossRef
Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases
Hongyu Chen, Junmin Wang, Caiyun Zhang, Peilun Ding, Shuxia Tian, Junming Chen, Guang Ji, Tao Wu
Biomedicine & Pharmacotherapy.2022; 153: 113341. CrossRef

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Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study: Seong Hyun Jeong, Seok Jin Kim, Dok Hyun Yoon, Yong Park, Hye Jin Kang, Youngil Koh, Gyeong-Won Lee, Won-Sik Lee, Deok-Hwan Yang, Young Rok Do, Min Kyoung Kim, Kwai Han Yoo, Yoon Seok Choi, Hwan Jung Yun, Jun Ho Yi, Jae-Cheol Jo, Hyeon-Seok Eom, Jae-Yong Kwak, Ho-Jin Shin, Byeong Bae Park, Shin Young Hyun, Seong Yoon Yi, Ji-Hyun Kwon, Sung Yong Oh, Hyo Jung Kim, Byeong Seok Sohn, Jong Ho Won, Se-Hyung Kim, Ho-Sup Lee, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2022;54(4):1268-1277. Published online December 30, 2021; DOI: https://doi.org/10.4143/crt.2021.1168

Abstract PDF Supplementary Material PubReader ePub

Purpose
Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).
Materials and methods
We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485).
Results
Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047).
Conclusion
Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Citations

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Sarcopenia attenuates the efficacy of PEGylated granulocyte colony-stimulating factor in preventing febrile neutropenia
Se-Il Go, Eun-Jeong Jeong, Woo Je Lee, Sungwoo Park, Mi Jung Park, Gyeong-Won Lee
Supportive Care in Cancer.2025;[Epub] CrossRef

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Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue: Yoon Seok Choi, Seok Jin Kim, Dae Sik Kim, Seh Jong Park, Yong Park, Hye Jin Shin, Kwang-Yoon Jung, Seung-Kuk Baek, Bong Kyung Shin, Jung Woo Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; Cancer Res Treat. 2007;39(3):109-115. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.109

Abstract PDF PubReader ePub

Purpose

Tumor cells are known to express hypoxia-related proteins such as glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor cells to survive under sustained hypoxic microenvironments, and the surviving tumor cell under hypoxia may develop a more aggressive phenotype and so result in a poor prognosis.

Materials and Methods

The Glut-1 expression was analyzed by immunohistochemistry, and its association with the prognosis was assessed in 60 patients with squamous cell carcinoma of the tongue.

Results

The Glut-1 expression was diffuse with a membranous pattern, and the median percentage of Glut-1 positive tumor cells was 60% (range: 0.0~90.0%). A high Glut-1 expression (the percentage of positive tumor cells ≥ the median value, 60%) was associated with the location of primary lesion, lymph node metastasis status and disease stage (p<0.05). The expression of Glut-1 was correlated with the Ki-67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31 staining, was also correlated with the Glut-1 expression although its significance is weak (r=0.267, p=0.039). On the univariate analysis, the group with a high Glut-1 expression showed poorer overall survival than the group with a low Glut-1 expression (p<0.05). However, the Glut-1 expression failed to show any independent prognostic significance on the multivariate analysis.

Conclusion

The expression of Glut-1 may be useful for predicting the prognosis and determining the treatment strategy for the management of squamous cell carcinoma of the tongue.

Citations

Citations to this article as recorded by

Study of expression of GLUT-1 in oral potentially malignant disorders and oral squamous cell carcinoma: An immuno-histochemical analysis
Shylaja K. Attur, Anil Patel, Kailash M. Attur
Journal of Oral and Maxillofacial Pathology.2024; 28(1): 70. CrossRef
Prognostic value of glycolysis markers in head and neck squamous cell carcinoma: a meta-analysis
Yanting Wang, Yuanyuan Li, Laibo Jiang, Xianyue Ren, Bin Cheng, Juan Xia
Aging.2021; 13(5): 7284. CrossRef
The Role of Glucose Transporters in Oral Squamous Cell Carcinoma
Heinrich Botha, Camile S. Farah, Kendrick Koo, Nicola Cirillo, Michael McCullough, Rita Paolini, Antonio Celentano
Biomolecules.2021; 11(8): 1070. CrossRef
Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy
Angara Zambrano, Matías Molt, Elena Uribe, Mónica Salas
International Journal of Molecular Sciences.2019; 20(13): 3374. CrossRef
Can increased metabolic status be a grading tool for oral squamous cell carcinoma? A glucose transporter 1 immunoexpression study
Abikshyeet Panda, Alokenath Bandyopadhyay, Gouse Mohiddin, Malvika Raghuvanshi, SanjayKumar Sahoo, Lipsa Bhuyan
Nigerian Journal of Surgery.2019; 25(2): 203. CrossRef
Plumbagin‐mediating GLUT1 suppresses the growth of human tongue squamous cell carcinoma
S Na, J Zhang, X Zhou, A Tang, D Huang, Q Xu, D Xue, J Qiu
Oral Diseases.2018; 24(6): 920. CrossRef
Expression of GLUT-1 in oral squamous cell carcinoma in tobacco and non-tobacco users
Neha Azad, Malti Kumari Maurya, Meenakshi Kar, Madhu Mati Goel, Ajay Kumar Singh, Mala Sagar, Divya Mehrotra, Vijay Kumar
Journal of Oral Biology and Craniofacial Research.2016; 6(1): 25. CrossRef
Distribution of Hypoxia-Inducible Factor-1α and Glucose Transporter-1 in Human Tongue Cancers
Marcelo Gadelha Vasconcelos, Rodrigo Gadelha Vasconcelos, Denise Hélen Imaculada Pereira de Oliveira, Edilmar de Moura Santos, Leão Pereira Pinto, Éricka Janine Dantas da Silveira, Lélia Maria Guedes Queiroz
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Expression of glucose transporters in cancers
Leszek Szablewski
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2013; 1835(2): 164. CrossRef
T-Type Ca2+Channels in Normal and Abnormal Brain Functions
Eunji Cheong, Hee-Sup Shin
Physiological Reviews.2013; 93(3): 961. CrossRef
Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars
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Hypoxia-related protein expression and its clinicopathologic implication in carcinoma of unknown primary
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