Cancer Research and Treatment

Original Articles

Nivolumab in Relapsed or Refractory Primary Central Nervous System Lymphoma: Multicenter, Retrospective Study: Jun Ho Yi, Seok Jin Kim, Sang-A Kim, Jongheon Jung, Dok Hyun Yoon; Received June 5, 2024 Accepted August 14, 2024 Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.531 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Given that 40%-50% of primary central nervous system lymphoma (PCNSL) tissues exhibit aberrancy on 9p24.1, immune checkpoint inhibitors (ICI) may work for the disease.
Materials and Methods
To define the role of ICIs in PCNSL, we carried out a nationwide retrospect analysis for 22 patients who had been treated with nivolumab monotherapy for relapsed or refractory PCNSL.
Results
The median age at diagnosis was 66, and male: female ratio was 1:1. Patients received nivolumab after a median of 3 lines (range, 2 to 6) of therapy and at the median age of 67 years (range, 37 to 82 years). Eleven patients (50%) were refractory to the last treatment prior to nivolumab. With a median follow-up duration of 22.3 months (95% confidence interval [CI], 13.1 to 31.5), nine patients (41%) had an objective response (6 complete responses, 3 partial responses), and the median duration of response was 20.9 months (95% CI, 1.7 to 40.0). The median progression-free survival and overall survival were 2.1 months (95% CI, 0.2 to 4.0) and 18.9 months (95% CI, 5.0 to 32.8), respectively. Nivolumab was generally well-tolerated as no patients required dose reduction and only two patients required delay of treatment.
Conclusion
Our study suggests that nivolumab can be a reasonable option with the durable response for RR PCNSL.

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Lung cancer

Sequential Treatment with an Immune Checkpoint Inhibitor Followed by a Small-Molecule Targeted Agent Increases Drug-Induced Pneumonitis: Jongheon Jung, Hyae Young Kim, Dong-Gil Kim, Seog Yun Park, A Ra Ko, Ji-Youn Han, Heung Tae Kim, Jin Soo Lee, Youngjoo Lee; Cancer Res Treat. 2021;53(1):77-86. Published online August 6, 2020; DOI: https://doi.org/10.4143/crt.2020.543

Abstract PDF Supplementary Material PubReader ePub

Purpose
Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis.
Materials and Methods
In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated.
Results
Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).
Conclusion
Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.

Citations

Citations to this article as recorded by

Toxicities associated with sequential or combined use of immune checkpoint inhibitors and small targeted therapies in non-small cell lung cancer: A critical review of the literature
Anne-Laure Désage, Michael Duruisseaux, Claire Lafitte, Sophie Bayle-Bleuez, Christos Chouaid, Pierre Fournel, Thomas Pierret
Cancer Treatment Reviews.2024; 129: 102805. CrossRef
Deep learning for predicting the risk of immune checkpoint inhibitor-related pneumonitis in lung cancer
M. Cheng, R. Lin, N. Bai, Y. Zhang, H. Wang, M. Guo, X. Duan, J. Zheng, Z. Qiu, Y. Zhao
Clinical Radiology.2023; 78(5): e377. CrossRef
Evaluating Pneumonitis Incidence in Patients with Non–small Cell Lung Cancer Treated with Immunotherapy and/or Chemotherapy Using Real-world and Clinical Trial Data
Qi Liu, Chenan Zhang, Yue Huang, Ruihao Huang, Shiew-Mei Huang, Erin Larkins, Liza Stapleford, Donna R. Rivera, Paul G. Kluetz, Shenggang Wang, Hao Zhu, James Weese, Elizabeth Cromartie, Mahder Teka, Sheetal Walters, Frank Wolf, Thomas D. Brown
Cancer Research Communications.2023; 3(2): 258. CrossRef
Pulmonary toxicity in driver gene positive non-small cell lung cancer therapy
Yi-Pu Zhao, Yong Long
Current Medical Research and Opinion.2022; 38(8): 1369. CrossRef
Immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer: A review
Yuxuan Hao, Xiaoye Zhang, Li Yu
Frontiers in Oncology.2022;[Epub] CrossRef
Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster Single Gene EGFR Testing Using the Idylla™ EGFR Testing Platform
Norbert Banyi, Deepu Alex, Curtis Hughesman, Kelly McNeil, Diana N. Ionescu, Carmen Ma, Stephen Yip, Barbara Melosky
Current Oncology.2022; 29(10): 7900. CrossRef
Sequential or combined immune checkpoint inhibitors and targeted therapy: Navigating uncharted waters
K. El Husseini, M. Wislez
Respiratory Medicine and Research.2021; 79: 100820. CrossRef
Multiple drugs

Reactions Weekly.2021; 1863(1): 255. CrossRef
Deep learning model enables the discovery of a novel immunotherapeutic agent regulating the kynurenine pathway
Jeong Hun Kim, Won Suk Lee, Hye Jin Lee, Hannah Yang, Seung Joon Lee, So Jung Kong, Soyeon Je, Hyun-Jin Yang, Jongsun Jung, Jaekyung Cheon, Beodeul Kang, Hong Jae Chon, Chan Kim
OncoImmunology.2021;[Epub] CrossRef

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Hematologic malignancy

Cyclophosphamide, Bortezomib, and Dexamethasone Consolidation in Patients with Multiple Myeloma after Stem Cell Transplantation: The KMM130 Study: Jongheon Jung, Kihyun Kim, Sung-Hoon Jung, Sung-Soo Yoon, Jae Hoon Lee, Jin Seok Kim, Ho-Jin Shin, Soo-Mee Bang, Sang Kyun Sohn, Cheolwon Suh, Dok Hyun Yoon, Sun-Young Kong, Chang-Ki Min, Hyeon-Seok Eom, The Korean Multiple Myeloma Working Party; Cancer Res Treat. 2023;55(2):693-703.; DOI: https://doi.org/10.4143/crt.2022.952

Abstract PDF Supplementary Material PubReader ePub

Purpose
A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma.
Materials and Methods
In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m² orally on days 1, 8, and 15, and bortezomib 1.3 mg/m² subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23.
Results
At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade ≥ 3 neuropathy observed.
Conclusion
These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327).

Citations

Citations to this article as recorded by

Is There Still a Role for Stem Cell Transplantation in Multiple Myeloma?
Morie A. Gertz
Hematology/Oncology Clinics of North America.2024; 38(2): 407. CrossRef
Ginsenoside Rg1 inhibits multiple myeloma and overcomes bortezomib resistance through AMPK-mTOR pathway
Li Lin, Dong Chen, Shuangyue Li, Tiantian Wang
Heliyon.2024; 10(13): e33935. CrossRef

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