Severe Central Nervous System Fungal Infection Following Tirabrutinib Administration in a Patient with Refractory Primary Central Nervous System Lymphoma: A Case Report

Abstract

Tirabrutinib, an inhibitor of Bruton's tyrosine kinase—a hub gene for primary central nervous system lymphoma proliferation—is a novel therapeutic agent for relapsed and refractory primary central nervous system lymphoma. We report a case of severe Aspergillus encephalitis following tirabrutinib administration. A man in his 50s suddenly presented with left sided hemiparesis, and neuroimaging suggested a primary central nervous system lymphoma in the right parietal lobe. The results of the tissue biopsy revealed a diagnosis of CD20-positive diffuse large B-cell lymphoma. Despite treatment with high-dose methotrexate combined with rituximab, neurological symptoms rapidly deteriorated. We suspected that the growth of the tumor led to an impending brain herniation, so we planned radiation therapy. However, the patient contracted coronavirus disease 2019. Therefore, we decided to administer tirabrutinib, which can be administered orally. The tumor shrank dramatically, and improvement in neurological symptoms was observed. However, due to onset of liver dysfunction, tirabrutinib was discontinued. Immediately thereafter, the primary central nervous system lymphoma began to progress again, necessitating the re-administration of tirabrutinib. Concurrently, a cerebral abscess developed in the basal ganglia. Subsequently, a fatal subcortical hemorrhage occurred. Brain tissue obtained during hematoma evacuation led to a histological diagnosis of Aspergillus cerebral vasculitis. We started treatment with voriconazole first, and then added amphotericin B, but multiple cerebral abscesses developed and progressed to encephalitis, resulting in death. Burton's tyrosine kinase is a gene crucial for the general antifungal immunity, and when using Burton's tyrosine kinase inhibitors, physician should always be mindful of preventing, detecting early, and addressing fungal infections to avoid fatal adverse events like in this case.

Introduction

The prognosis for primary central nervous system lymphoma (PCNSL) has improved significantly over the past 20 years. Advances in chemotherapy beginning with the high-dose methotrexate (HD-MTX) therapy reported by Glass in 1994 have reliably led to improved prognosis for PCNSL.¹⁾ In recent years, the dramatic efficacy of R-MPV therapy—a multi-agent combination based on HD-MTX (methotrexate, procarbazine, vincristine) with the addition of rituximab has been demonstrated.²⁾ According to the latest NCCN guidelines for central nervous system cancer 2025³⁾ and EHA-ESMO guideline for PCNSL,⁴⁾ R-MPV therapy is listed as the preferred initial therapy for PCNSL. Furthermore, adding consolidation therapy with whole brain irradiation, high-dose cytarabine, or autologous stem cell transplantation is considered optimal.^3,4) However, the preferred therapy for relapsed or refractory PCNSL (r/r PCNSL) cases resistant to recommended treatment is listed as "none".^3,4) As an additional recommendation beyond the guidelines, rechallenging with R-MPV therapy is considered optimal.^3,4) Other options include the Burton's type tyrosine kinase (BTK) inhibitor Ibrutinib.^3,4) BTK, a tyrosine kinase, is a hub gene involved in both B-cell receptor pathway and Toll-like receptor pathway, a signaling system involved in the proliferation of B-cell lymphoma. Inhibiting BTK enables the inhibition of both the downstream PI3K/AKT/mTOR pathway and the NF-κB pathway that leads to tumor shrinkage.⁵⁾

Recently, we had the opportunity to administer a BTK inhibitor, tirabrutinib (TIR) to a PCNSL case that demonstrated resistance to initial R-MTX therapy. Although we observed a dramatic reduction in tumor size following TIR in this case, we are reporting it because the patient experienced a severe central nervous system fungal infection, which is a likely adverse event associated with TIR therapy.

Case Report

A man in his 50s suddenly presented with left-sided hemiparesis and hemi-numbness. Brain imaging revealed an intra-parenchymal mass homogeneously enhanced in the right parietal lobe (Figure 1 A-C). Biopsy under craniotomy was performed, resulting in a diagnosis of CD20-positive diffuse large B cell lymphoma. Two cycles of high-dose MTX therapy combined with rituximab were administered, but the patient showed rapid worsening of hemiparesis with impaired consciousness. Based on neuroimaging findings, the rapid growth of the tumor and worsening of surrounding edema led us to conclude that the patient is experiencing impending brain herniation (Figure 1 D-F). While undergoing steroid pulse therapy and considering a transition to radiation therapy, the patient developed coronavirus disease 2019 infection, and favipiravir therapy was started. Since it was essential to reduce the tumor size by any means necessary, we attempted to use TIR; as a result, the patient's level of consciousness and neurological deficits improved rapidly, and rapid tumor shrinkage was also observed on neuroimaging (Figure 1 J-L). However, TIR administration was discontinued after 5 weeks due to liver dysfunction. Subsequently, the tumor began to grow again, and small abscess lesions appeared and scattered throughout both cerebral hemispheres. (Figure 1 M-R) A chest computed tomography (CT) scan revealed left pulmonary fungal infection, prompting initiation of voriconazole (VCZ) administration concurrently with brain focal radiotherapy (Figure 2 A-D). However, on the 12th day, after VCZ administration, the patient fell into a coma and CT scan revealed a massive subcortical hemorrhage, necessitating emergency hematoma evacuation. A biopsy of the brain tissue surrounding the hematoma revealed PAS-positive Aspergillus hyphae in the small vessels of the brain parenchyma (Figure 2 G-J). While continuing VCZ administration, TIR was restarted at 75% dose for a total of 27 weeks. Although brain lymphoma achieved radiographic complete remission, no therapeutic effect was observed for the multiple brain abscesses, therefore, we added amphotericin B to the VCZ in an effort to bring the abscess under control (Figure 2 K-P). Continuation of TIR administration prevented the worsening of the patient's neurological symptoms, and imaging findings continued to show a trend toward resolution of the PCNSL. However, findings consistent with multiple brain abscesses gradually worsened, and extensive inflammation in the brain parenchyma, consistent with aspergillus encephalitis, was observed (Figure 2 Q-V). Although TIR and VCZ with amphotericin B administration continued thereafter, the patient's general condition gradually deteriorated, leading to death from multiple organ failure. The survival period was 20 months from the time of histological diagnosis of PCNSL.

Figure 1

Changes in axial MRI findings from onset to the first TIR administration.

A, D, G, J, M, N: Axial FLAIR images.

B, E, H, K, O, P: Axial diffusion-weighted images (DWI).

C, F, I, L, Q, R: Axial gadolinium enhanced T1-weighted images.

A-C: The initial MRI revealed a tumor in the right parietal lobe white matter that showed homogeneous enhancement and high signal intensity on DWI, with mild surrounding edema.

D-F: Although the patient had undergone two cycles of high-dose MTX therapy in combination with rituximab, significant tumor enlargement and worsening of surrounding edema were observed, suggesting a state of impending brain herniation.

G-L: One week after TIR administration, a marked tumor shrinkage was observed (G-I), and after 4 weeks, further tumor shrinkage and improvement in surrounding edema were demonstrated (I-L).

M-R: Immediately after discontinuing TIR due to onset of liver dysfunction, the tumor enhancement had almost completely disappeared, and the surrounding edema had become minimal. However, a spot (yellow arrow) showing high signal intensity on DWI has appeared in the right caudate nucleus.

FLAIR: fluid attenuated inversion recovery, MRI: magnetic resonance imaging, MTX: methotrexate, TIR: tirabrutinib

Figure 2

Changes in lung and brain lesions following COVID-19 infection.

A-D: Axial CT images of lung.

E, F: Axial diffusion-weighted images (DWI).

G, H: Axial CT images of brain.

I, J: Histological findings of biopsied brain tissue (I: H&E staining, ×100, J: PAS staining, ×100).

K-V: Changes in axial brain MRI images during treatment for PCNSL and cerebral mycosis.

A-D: The patient presented with left-sided pneumonia following COVID-19 infection, but showed improvement in pneumonia with favipiravir therapy. However, around the third week after TIR administration, a purulent lesion (indicated by the yellow dashed circle) accompanied by a cavity suggestive of fungal infection appeared in the left lung field; this showed improvement with administration of VCZ.

E-F: During the TIR interval, the number of lesions showing high signal intensity on DWI has increased, and at the same time, findings suggestive of abscesses have begun to appear in the right basal ganglia and subcortical regions.

G-H: On the 12th day after the re-administration of TIR, the patient developed fatal subcortical hemorrhage in right parietal lobe.

I-J: In the brain tissue surrounding the hematoma, there was a marked infiltration of inflammatory cells, primarily neutrophils, along with clusters of Aspergillus fungi with PAS-positive branches, which had infiltrated the walls of the cerebral micro-vessels.

K-V: Since no improvement in the multiple brain abscesses was observed 1 month after the start of VCZ administration (K-M), amphotericin B was added to the regimen; however, no improvement was seen thereafter, and the condition continued to deteriorate, progressing to encephalitis at 2 months (N-P), 3 months (Q-S), and 4 months (T-V) after the start of anti-fungal drugs administration. However, as TIR was also being administered, the growth of the lymphoma was suppressed.

COVID-19: coronavirus disease 2019, CT: computed tomography, H&E: hematoxylin and eosin, PAS: periodic acid-schiff, MRI: magnetic resonance imaging, PCNSL: primary central nervous system lymphoma, TIR: tirabrutinib, VCZ: voriconazole

Discussion

The 2024 Japanese Guidelines for the Diagnosis and Treatment of Brain Tumors recommend the following three treatment options for r/r PCNSL with a lower level of evidence.⁶⁾

(1) For patients achieving long-term response with initial HD-MTX therapy, propose treatment including HD-MTX therapy (recommendation Level 2C).

(2) Weakly recommend TIR monotherapy (recommendation Level 2B).

(3) If whole brain irradiation was not administered during initial treatment, or if additional irradiation is feasible, weakly recommend whole-brain irradiation at recurrence (recommendation Level 2B).

Level 2B recommendations indicate that while the level of evidence supporting the treatment is low, the benefits of the treatment may outweigh the harms, and therefore its implementation is proposed.

Regarding the administration of TIR, a BTK inhibitor for r/r PCNSL, it received insurance approval in Japan in March 2020. The proof of concept for its efficacy and safety came from the results of the domestic Phase I/II trial (ONO-4059-02).^5,7) In addition to demonstrating clear efficacy—including the advantages of being an oral medication, marked tumor shrinkage effects observed early in this treatment and rapid, multifaceted improvements in quality of life—it also revealed the actual nature of its adverse events (AEs).^5,7) Specifically, in a clinical trial involving 44 patients with r/r-PCNSL and a Karnofsky performance status of 70 or higher, the overall response rate was 64%, with a high complete response rate of 60% among these responses.⁵⁾ The median progression-free survival in the 480 mg fasting dose group was 5.8 months, and the median overall survival was not reached during the median follow-up period of 9.1 months (range, 1.4-19.4).⁵⁾ Furthermore, according to quality of life assessment using the QOQ-C30, improvement was observed and maintained through cycles 3-17 of TIR administration (1 cycle: 28 days).⁷⁾ This improvement encompassed not only global health status but also emotional functioning, with both showing sustained improvement.⁷⁾ AEs were generally mild to moderate, with the most common ones being skin disorders (54.5%), primarily rash (31.8%), neutropenia (22.7%), and lymphopenia (15.9%).⁵⁾ One case developed hematuria and pulmonary aspergillosis, and one case died from severe pneumonia (Pneumocystis jirovecii pneumonia).⁵⁾ Therefore, adequate prophylactic treatment for rash and pneumonia should be considered during TIR administration.⁵⁾

This case involved PCNSL occurring in a healthy man in his 50s, who showed complete resistance to two cycles of HD-MTX based chemotherapy and experienced rapid neurological deterioration. Whole brain radiation therapy was planned, but the patient developed COVID-19 infection. From a rescue perspective, we started with TIR administration. Though TIR ultimately demonstrated dramatic efficacy, however, severe pulmonary aspergillosis and severe intracerebral hemorrhage due to Aspergillus cerebral vasculitis developed after TIR administration. Upon immediate administration of antifungal agents, the findings of the lung abscess showed a trend toward improvement, however, no improvement was achieved in the multiple brain abscesses. It cannot be denied that the patient had immune-compromised conditions, such as prior MTX-based chemotherapy, steroid pulse therapy, and the onset and treatment of COVID-19 infection. We believe that administering TIR to patients in such an immune-compromised state led to severe central nervous system infections.

From the March 2020 insurance approval through the end of 2025, the TIR marketing company reported AEs in cases of TIR administration for r/r PCNSL.⁸⁾ A total of 584 cases and 1,146 AEs were recorded, of which 274 cases and 394 events were classified as serious AEs. Examining the breakdown of severe infectious diseases, particularly pneumonia, revealed that the primary diagnoses were: 15 cases of pneumonia, nine cases of Pneumocystis jirovecii pneumonia, five cases of pulmonary aspergillosis, and four cases of COVID-19 pneumonia.⁸⁾ The presented case involved concurrent pulmonary aspergillosis and Aspergillus cerebral vasculitis, but this AE report includes one case of fungal encephalitis.⁸⁾ Indications for TIR beyond r/r PCNSL include primary macroglobulinemia and lymphoplasmacytic lymphoma.⁸⁾ Among the 182 cases reporting serious AEs following TIR administration in these conditions, there were two reports of pulmonary aspergillosis and two reports of cerebral aspergillosis.⁸⁾ These two cases are highly likely to have been concurrent.

A search for cases of Aspergillus infection as an AEs associated with BTK inhibitors identified 11 cases, including this presented case^9-17) (Table 1). Chronic lymphocytic leukemia (CLL) was the most common underlying condition, with eight cases receiving BTK inhibitors, four cases receiving ibrutinib, five receiving acalabrutinib, and one receiving obinutuzumab. Only two cases from Japan had received TIR for PCNSL,¹⁵⁾ and there had been no previous cases of severe intracerebral hemorrhage resulting from cerebral vasculitis. The primary site of Aspergillus infection was pulmonary lesions in nine cases, and cerebral lesions developed as a complication in six cases. Though many reports indicate that BTK inhibitors were discontinued once aspergillosis was confirmed, in this case, discontinuing TIR would have led to immediate progression of PCNSL, so we had no choice but to continue treatment regimen. The time interval between BTK inhibitor administration and the onset of Aspergillus infection ranged from 14 days to 1.5 years, varying from case to case. According to a review by Gilbert et al¹⁸⁾ among 25,215 patients treated with BTK inhibitors for malignant tumors, primarily CLL, 736 (2.9%) developed invasive fungal infections (IFI), of which 227 (30.8%) were Aspergillus infections. Among the 211 case reports of IFI, Aspergillus infection was the most common, accounting for 107 cases (50.7%), followed by Cryptococcus, which accounted for 33 cases (15.6%). The time from BTK inhibitor administration to confirmation of Aspergillus infection was 2.3 months, suggesting that discontinuation of BTK inhibitors early improves survival rates. Moreal et al¹⁹⁾ have published an excellent review on the management of IFI, emphasizing the importance of assessing IFI risk—particularly by evaluating recent viral infections and immunosuppressive states such as lymphocytopenia and elevated Interleukin-10 levels. For actual treatment, VCZ or isavuconazole is selected as first-line option, however, the authors states that isavuconazole is more strongly recommended because it does not cause renal toxicity or QT prolongation. For rapidly progressing or refractory cases, posaconazole or liposomal amphotericin B are recommended as second-line treatments. Moreal et al¹⁹⁾ argue that IFI should be effectively managed through proper risk assessment and therapeutic drug monitoring. In fact, a review of reported cases (Table 1) shows that VCZ monotherapy or amphotericin B had not demonstrated efficacy, whereas second- and third-generation antifungal agents have been shown to be effective.

Table 1

Reports of Cases of Fungal Infections Occurring after BTK Administration in Patients with Various Types of Cancer

Author (year)	BTK- inhibitor	Age/Gender	Primary pathology	Administration of corticosteroids	Period until IFI	IFI site	BTK inhibitor	Treatment of IFI	Suvival periods
* Chronic lymphocytic leukemia
Arthurs (2017)	Ibrutinib	62/M	CLL*	(-)	6 weeks	Lung	Discontinued	Voriconazole	Died, 5 months
Kreiniz (2018)	Ibrutinib	67/M	CLL	(-)	7 months	Lung	Not described	Voriconazole	Died, not described
Beresford (2019)	Ibrutinib	66/M	CLL	(-)	1 year	Brain	Discontinued	Voriconazole	Improved, alive
Nyga(2020)	Iburutinib	69/M	CLL	(-)	1 year	Lung and Brain	Discontinued	Amphotericin B and voriconazole to Isavuconazole	Improved, alive
Dunbar (2020)	Iburutinib	75/M	CLL	(-)	Not described	Lung and Liver	Discontinued	Amphotericin B and Posaconazole	Improved, alive
Alkharabsheh (2021)	Acalabrutinib with Obinutuzumab	62/M	CLL	(-)	3 months	Brain	Only obinutuzumab was discontinued	Amphotericin B and Isavuconazole	Improved, alive
Kitamura (2022)	Tirabrutinib	69/F	Primary CNS lymphoma	(-)	1.5 years	Paranasal sinus	Discontinued	Voriconazole	Not described
Walsh (2023)	Iburutinib to Zanubrutunib	76/M	Marginal zone lymphoma	(+), 6 months	6 months	Lung and Brain	Continued	Voriconazole	Died, several days
Blaize (2024)	Acalabrutinib	80/M	CLL	(+), 1 month	14 days	Lung and Brain	Discontinued	Voriconazole	Died, 61 days
Blaize (2024)	Acalabrutinib	68/F	CLL	(+), 2 weeks	33 days	Lung + Pneumocystic jirovecci	Discontinued	Sulfamethoxazol/Trimethoprim and Voriconazole	Died, 48 days
Blaize (2024)	Acalabrutinib	77/M	CLL	(-)	50 days	Lung	Discontinued	Isavuconazole	Died, 71 days
Akimoto (2026)	Tirabrutinib	55/M	Refractory CNS lymphoma	(+), Pulse therapy ×2	7 weeks	Lung and Brain	Continued	Voriconazole and Amphotericin B	Died, 20 months

In recent years, the importance of BTK in the immune response has been highlighted, and it has become clear that BTK plays a significant role in signal transduction in response to bacterial infections not only in neutrophils, macrophages, and platelets but also in microglia.^20,21) In particular, it has been demonstrated that BTK activates pattern recognition receptors on neutrophils, TLR9 signaling in macrophages, and the phagocytic capacity of microglia in the brain, particularly in response to fungal infections (primarily Aspergillus).^20-22) In other words, using BTK inhibitors in patients whose immune function has been compromised by prior chemotherapy or steroid therapy significantly increase the risk of fungal infections, particularly those caused by Aspergillus.²¹⁾ Therefore, monitoring β-D-glucan levels during treatment, conducting frequent imaging of the lungs and brain, ensuring immune function through early administration of GM-Colony-Stimulating Factor, and considering prophylactic antifungal therapy, such as isavuconazole (CRESEMBA^®) or posaconazole (NOXAFIL^®) should all be part of the treatment strategy.

The number of reports related to the efficacy and safety of administering TIR, a BTK inhibitor, for r/r PCNSL has been increasing in recent year. However, neuro-oncologists who routinely manage PCNSL should be aware that it can potentially cause severe fungal infections, as seen in this case. We aim to raise awareness about the reduced antifungal activity associated with BTK inhibitors to prevent fatal AEs as in this case.

Conflicts of Interest Disclosure

All authors have no conflict of interest. The authors have registered online self-reported COI Disclosure Statement Forms through the website of Japan Neurosurgical Society members.

References

• 1)  Glass J, Gruber ML, Cher L, et al. Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg. 1994; 81 (2): 188-95. doi.10.3171/jns.1994.81.2.0188
• 2)  Morris PG, Correa DG, Yahalom J, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013; 31 (31): 3971-3979. doi:10.1200/JCO.2013.50.4910
• 3)  Central nervous system cancers, version 3. J Natl Compr Canc Netw. 2025, NCCN Clinical Practice Guidelines in Oncology: 2025.
• 4)  Ferreri AJM, Illerhaus G, Doorduijin JK, et al. Primary central nervous system lymphomas: EHA-ESMO clinical practice guideline for diagnosis, treatment and follow up. Ann Oncol. 2024; 35 (6): 491-507. doi: 10.1016/j.amnonc.2013.11.010
• 5)  Narita Y, Nagane M, Mishima K, et al. Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. Neurol Oncol 2021; 23 (1): 122-33. doi: 10.1093/neuonc/noaa145
• 6)  Nagane M. Practical guidelines for Neuro-Oncology Adult Edition 2024. The Japan Society for Neuro-Oncology; Kanehara Shuppan, 2024. Chapter 3, Primary Central Nervous System Lymphoma; p. 175-8.
• 7)  Arakawa Y, Narita Y, Nagane M, et al. Karnofsky Performance Status and quality of life in patients with relapsed or refractory primary CNS lymphoma from a phase I/II study of tirabrutinib. Neuro-Oncol Adv 2023; 5 (1): vdad109. doi: 10.1093/noajnl/vdad109.
• 8)  ONO MEDICAL NAVI. https://www.ononavi1717.jp/system/files/2026-02/side_effect_VLX_indication_0.pdf
• 9)  Arthurs B, Wunderle K, Hsu M, et al. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia. Respir Med Case Rep. 2017; 21: 27-29. doi:10.1016/j-rmcr.2017.03.011
• 10)  Kreiniz N, Bejar J, Polliack A, et al. Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma. Hematol Oncol 2018: 36 (1); 349-54. DOI:10.1002/hon.2387.
• 11)  Beresford R, Dolot V, Foo H. Cranial aspergillosis in a patient receiving ibrutinib for chronic lymphocytic leukemia. Med Mycol Case Rep. 2019; 24: 27-9. doi:10/1016/j.mmcr.2019.02.005.
• 12)  Nyga R, Delette C, Mabille C, et al. Ibrutinib related cerebral aspergillosis successful treated with isavuconazole: a case report. Leuk Lymphoma. 2020; 61 (7): 1760-2. doi:10.1080/10428194.2020/1728749
• 13)  Dunbar A, Joose ME, de Bore F, at al. Invasive fungal infections in patient with treated with Burton's tyrosine kinase inhibitors. Neth J Med. 2020; 78 (5): 294-296.
• 14)  Alkharabsheh O, Alsayed A, Morlote DM, et al. Cerebral invasive aspergillosis in a case of chronic lymphocytic leukemia with Bruton tyrosine kinase inhibitor. Curr Oncol. 2021; 28: 837-41. doi:10.3390/curroncol28010081
• 15)  Kitamura W, Kuyama S. Paranasal sinus aspergillosis in a patient treated with tirabrutinib. Int J Hematol. 2022; 116: 645-6. doi:10.1007/s12185-022-03460-3
• 16)  Walsh M, Xu A, Ballas Z, at al. Disseminated fungal infection in a patient receiving zanubrutinib. Clin Case Rep. 2023; 11: e7564. doi:10.1002/ccr3.7564
• 17)  Blaize M, Thizy G, Boissonnas A, et al. Invasive aspergillosis with impaired neutrophil response against Aspergillus fumigatus in patient treated with acalabrutinib-findings from three cases. Int J Infect Dis. 2024;142: 107000. doi:10.1016/j.ijid.2024.107000
• 18)  Gilbert C, Blaize M, Fekkar A. Fungal infection in patient treated with Bruton tyrosine kinase inhibitor – from epidemiology to clinical outcome: a systematic review. Clin Microbiol Infect. 2025; 31 (5): 731-9. doi:10.1016/j.cmi.2024.12.032.
• 19)  Moreal C, Angelini J, Venturini S, et al. Management of invasive fungal infection: clinical strategies in Critical care from a multidisciplinary consensus. New Microbiol. 2025; 48: 211-4.
• 20)  Vargas-Blanco DA, Hepworth OW, et al. BTK inhibitor-induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-α. JCI Insight 2024: 9 (12); e176162. doi: 10.1172/jci.insight.176162
• 21)  Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary Central Nervous System Lymphoma. Cancer Cell 2017: 31 (6); 833-843. E5. Doi: 10.1016/j.ccell. 2017.04.012.
• 22)  Keany J, Gasser J, Gillet G, et al. Inhibition of Bruton's tyrosine kinase modulates microglial phagocytosis: therapeutic implications for Alzheimer's disease. J Neuroimmune Pharmacol. 2019; 14 (3): 448-461. doi:10.1007/s11481-019-09839-0