Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
- Study type(s): clinical trials, prospective, or retrospective studies published in the English language were considered eligible for this study;
- Study participant(s): patients of any age with R/R PCNSL, irrespective of subtypes, treated with ibrutinib monotherapy or combination therapy;
- Study outcome(s): reporting either efficacy or safety endpoints, including the Overall Response (ORR), Complete Response (CR), Partial Response (PR), Progression-Free Survival (PFS), Overall Survival (OS), and adverse events.
- Case reports and case series with ≤ 2 cases;
- Review articles;
- Studies that were published in a language other than English;
- Research that did not report the outcomes of interest listed above.
3. Results
3.1. Monotherapy
3.2. Combination Therapy
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Origin | Design | R/R Cases (n) | Median Age | Previous Treatment | Mono/Combined | Ibrutinib Dose | Median Follow-Up |
---|---|---|---|---|---|---|---|---|
Chamoun 2016 | France and Belgium | Retrospective study | 14 | 68 y (range 48–79) | High-dose methotrexate-based chemotherapy. The median number of previous therapies was 3 (range 2–9). | Monotherapy Four patients received steroids for cerebral edema | 560 mg once daily 1 patient received a 420 mg dose | N/A |
Lionakis 2017 | USA | Phase I clinical trial | 13 | 66 (range 49–87) | Median of 2 (range 1–6) prior treatments | Monotherapy window followed by DA-TEDDi-R combination therapy | 560–840 mg | N/A |
Grommes 2017 | USA | Phase I clinical trial | 13 | 69 (60–80) | All received high-dose methotrexate-based chemotherapy. Two received radiation. Median 2 (1–8) before treatment | Monotherapy | 560 and 840 mg | 479 days (range, 354–739) |
Grommes 2019 | USA | Phase I clinical trial | 9 | 62 y (range, 23–74) | High-dose methotrexate-based chemotherapy with a heterogeneous combination of rituximab, an alkylating agent, radiation therapy, and stem cell therapy | Ibrutinib-based combination therapy followed by ibrutinib monotherapy maintenance 2: HD-MTX plus ibrutinib 7: RTX-HD-MTX plus ibrutinib | 560 to 840 mg | 19.7 months (range, 12.7–27.1) |
Mao 2018 | China | Retrospective Study | 3 | N/A | High-dose methotrexate-based chemotherapy | Combined therapy | 560 mg once daily | N/A |
Soussain 2019 | France | Phase II clinical trial | 52 | 70 y (range, 52–81 y). | High-dose methotrexate-based chemotherapy | Monotherapy Steroids in initial four weeks for cerebral edema | 560 mg once daily | 25.7 months |
Lewis 2019 | Australia | Retrospective Study | 8 | 65 y | High-dose methotrexate-based chemotherapy with radiotherapy, rituximab, and other chemotherapy. Median 1 (0–3) before treatment | Monotherapy in some patients and combined therapy (radiation plus chemotherapy) in the rest. | Daily dose was 560 mg (range 420–840 mg); | 14 months |
Lauer 2020 | Germany | Retrospective Study | 5 | 63 y (range: 53–82) | All patients were heavily pretreated (median of two prior treatment regimens), with 100% of patients receiving high-dose cytarabine and/or HD-MTX. Some received high-dose chemotherapy and autologous stem cell transplantation. | Monotherapy in some patients and combined therapy (radiation plus chemotherapy) in the rest. | 560 mg once daily | 427 days (range: 75–711) |
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Nepal, G.; Khurana, M.; Bucheli, D.H.; Bhandari, S.; Joshi, U.; Bhagat, R.; Rehrig, J.H.; Pudasainee, P.; Shing, Y.K.; Ortiz, J.F.; et al. Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review. Neurol. Int. 2022, 14, 99-108. https://doi.org/10.3390/neurolint14010009
Nepal G, Khurana M, Bucheli DH, Bhandari S, Joshi U, Bhagat R, Rehrig JH, Pudasainee P, Shing YK, Ortiz JF, et al. Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review. Neurology International. 2022; 14(1):99-108. https://doi.org/10.3390/neurolint14010009
Chicago/Turabian StyleNepal, Gaurav, Mahika Khurana, Domenica Herrera Bucheli, Siddhartha Bhandari, Utsav Joshi, Riwaj Bhagat, Jessica Holly Rehrig, Prasun Pudasainee, Yow Ka Shing, Juan Fernando Ortiz, and et al. 2022. "Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review" Neurology International 14, no. 1: 99-108. https://doi.org/10.3390/neurolint14010009