1.Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy
Jii Bum LEE ; Hye Ryun KIM ; Sang-Jun HA
Immune Network 2022;22(1):e2-
Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers.The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.
2.Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia
Yundeok KIM ; Tae-Hwa GO ; Jaeyeon JANG ; Jii Bum LEE ; Seung Taek LIM ; Kwang Yong SHIM ; Jong In LEE ; Jee Hyun KONG
The Korean Journal of Internal Medicine 2021;36(6):1450-1458
Background/Aims:
Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database.
Methods:
This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]).
Results:
The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS.
Conclusions
Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.
3.Characteristics and treatment patterns in older patients with locally advanced head and neck cancer (KCSG HN13-01)
Eun Joo KANG ; Yun-Gyoo LEE ; Bhumsuk KEAM ; Jin-Hyuk CHOI ; Jin-Soo KIM ; Keon Uk PARK ; Kyoung Eun LEE ; Hyo Jung KIM ; Keun-Wook LEE ; Min Kyoung KIM ; Hee Kyung AHN ; Seong Hoon SHIN ; Jii Bum LEE ; Jung Hye KWON ; Hye Ryun KIM ; Sung-Bae KIM ; Hwan Jung YUN
The Korean Journal of Internal Medicine 2022;37(1):190-200
Background/Aims:
Treatment decisions for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are complicated, and multi-modal treatments are usually indicated. However, it is challenging for older patients to complete treatments. Thus, we investigated disease characteristics, real-world treatment, and outcomes in older LA-HNSCC patients.
Methods:
Older patients (aged ≥ 70 years) were selected from a large nationwide cohort that included 445 patients with stage III–IVB LA-HNSCC from January 2005 to December 2015. Their data were retrospectively analyzed and compared with those of younger patients.
Results:
Older patients accounted for 18.7% (83/445) of all patients with median age was 73 years (range, 70 to 89). Proportions of primary tumors in the hypopharynx and larynx were higher in older patients and older patients had a more advanced T stage and worse performance status. Regarding treatment strategies of older patients, 44.5% of patients received concurrent chemoradiotherapy (CCRT), 41.0% underwent surgery, and 14.5% did not complete the planned treatment. Induction chemotherapy (IC) was administered to 27.7% (23/83) of older patients; the preferred regimen for IC was fluorouracil and cisplatin (47.9%). For CCRT, weekly cisplatin was prescribed 3.3 times more often than 3-weekly cisplatin (62.2% vs. 18.9%). Older patients had a 60% higher risk of death than younger patients (hazard ratio, 1.6; p = 0.035). Oral cavity cancer patients had the worst survival probability.
Conclusions
Older LA-HNSCC patients had aggressive tumor characteristics and received less intensive treatment, resulting in poor survival. Further research focusing on the older population is necessary.
4.Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma
Jii Bum LEE ; Hyung Soon PARK ; Sejung PARK ; Hyo Jin LEE ; Kyung A KWON ; Young Jin CHOI ; Yu Jung KIM ; Chung Mo NAM ; Nam Hoon CHO ; Beodeul KANG ; Hyun Cheol CHUNG ; Sun Young RHA
Cancer Research and Treatment 2019;51(4):1578-1588
PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.
Asian Continental Ancestry Group
;
Carcinoma, Renal Cell
;
Disease-Free Survival
;
Humans
;
Nephrectomy
;
Prognosis
;
Prospective Studies
;
Retrospective Studies
5.First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer
Minkyu JUNG ; Jii Bum LEE ; Hyo Song KIM ; Woo Sun KWON ; Hyun Ok KIM ; Sinyoung KIM ; Myunghwan PARK ; Wuhyun KIM ; Ki-Young CHOI ; Taegwon OH ; Chang-Yuil KANG ; Hyun Cheol CHUNG ; Sun Young RHA
Cancer Research and Treatment 2024;56(1):208-218
Purpose:
BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials and Methods:
Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses.
Results:
Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients.
Conclusion
BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.
6.Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea
Jii Bum LEE ; Minkyu JUNG ; June Hyuk KIM ; Bo Hyun KIM ; Yeol KIM ; Young Seok KIM ; Byung Chang KIM ; Jin KIM ; Sung Ho MOON ; Keon-Uk PARK ; Meerim PARK ; Hyeon Jin PARK ; Sung Hoon SIM ; Hong Man YOON ; Soo Jung LEE ; Eunyoung LEE ; June Young CHUN ; Youn Kyung CHUNG ; So-Youn JUNG ; Jinsoo CHUNG ; Eun Sook LEE ; Hyun Cheol CHUNG ; Tak YUN ; Sun Young RHA
Cancer Research and Treatment 2021;53(2):323-329
At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.
7.Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea
Jii Bum LEE ; Minkyu JUNG ; June Hyuk KIM ; Bo Hyun KIM ; Yeol KIM ; Young Seok KIM ; Byung Chang KIM ; Jin KIM ; Sung Ho MOON ; Keon-Uk PARK ; Meerim PARK ; Hyeon Jin PARK ; Sung Hoon SIM ; Hong Man YOON ; Soo Jung LEE ; Eunyoung LEE ; June Young CHUN ; Youn Kyung CHUNG ; So-Youn JUNG ; Jinsoo CHUNG ; Eun Sook LEE ; Hyun Cheol CHUNG ; Tak YUN ; Sun Young RHA
Cancer Research and Treatment 2021;53(2):323-329
At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.