
==== Front
J Med Case Rep
J Med Case Rep
Journal of Medical Case Reports
1752-1947
BioMed Central London

39256774
4757
10.1186/s13256-024-04757-z
Case Report
Ibrutinib as treatment for Bing–Neel syndrome reclassified as glioblastoma: a case report
Gravesen Charlotte Dahl charlotte@gravesen.us

1
Chanchiri Imanl 2
Kristensen Ida Bruun 2
Jensen Martin Bang 3
Harbo Frederik Severin Gråe 4
Dahlrot Rikke Hedegaard 15
1 https://ror.org/00ey0ed83 grid.7143.1 0000 0004 0512 5013 Department of Oncology, Odense University Hospital, Odense, Denmark
2 https://ror.org/00ey0ed83 grid.7143.1 0000 0004 0512 5013 Department of Hematology, Odense University Hospital, Odense, Denmark
3 https://ror.org/00ey0ed83 grid.7143.1 0000 0004 0512 5013 Department of Neurosurgery, Odense University Hospital, Odense, Denmark
4 https://ror.org/00ey0ed83 grid.7143.1 0000 0004 0512 5013 Department of Radiology, Odense University Hospital, Odense, Denmark
5 https://ror.org/03yrrjy16 grid.10825.3e 0000 0001 0728 0170 Department of Clinical Research, University of Southern Denmark, Odense, Denmark
11 9 2024
11 9 2024
2024
18 42428 3 2023
3 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Glioblastoma is a highly malignant disease with limited treatment options. Ibrutinib, a covalent Bruton tyrosine kinase inhibitor, is an oral agent with manageable side effects used for hematological diseases including Waldenström macroglobulinemia. We present the case of a 69-year-old Caucasian male patient treated with ibrutinib for suspected Bing–Neel syndrome (BNS), which following a biopsy, was reclassified as glioblastoma.

Case presentation

In December 2018, a 69-year-old Caucasian male patient was diagnosed with Waldenström macroglobulinemia. As the patient was asymptomatic, without bone marrow failure or high M-component count, watchful waiting was initiated. Due to increasing neurological symptoms, the patient, based on magnetic resonance imaging, was diagnosed with Bing–Neel syndrome in May 2019. The patient received different treatments before starting ibrutinib monotherapy in August 2019 due to disease progression, both on magnetic resonance imaging and clinically. The patient remained clinically stable for 7 months. In March 2020, the patient developed headaches, and both magnetic resonance imaging and a biopsy revealed glioblastoma IDH-wildtype. Treatment was changed in line with the new diagnosis, but the patient died at the end of 2020.

Conclusion

We present a case in which a patient with glioblastoma IDH-wildtype remained clinically stable for 7 months when treated with ibrutinib monotherapy, which is similar to what would be expected for the standard treatment for glioblastoma. To our knowledge, this is the first patient receiving ibrutinib for a glioblastoma IDH-wildtype with a meaningful clinical outcome. Our case may therefore support previous nonclinical findings, indicating a therapeutic value of ibrutinib in patients with glioblastoma and support for further investigation of ibrutinib as a possible treatment for glioblastoma.

Keywords

Glioma
Glioblastoma
Bing–Neel syndrome
Ibrutinib
Case report
issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
==== Body
pmcIntroduction

Glioblastoma IDH-wildtype (GBM) is a highly malignant World Health Organization (WHO) grade four brain tumor, with limited treatment options. Despite aggressive treatment, consisting of maximal safe surgery and radiotherapy with concomitant and adjuvant temozolomide (TMZ), prognosis remains poor [1]. Besides TMZ, only a few drugs have shown a clinical effect in either the primary or recurrent setting, primarily due to limited penetration of the blood–brain barrier. Here we present a case, with a patient treated with ibrutinib for suspected Bing–Neel syndrome (BNS), which following a biopsy, was reclassified as GBM.

Case

In December 2018, a 69-year-old Caucasian male patient was referred to the department of hematology from his general practitioner due to the abnormal presence of serum immunoglobulin (Ig) G lambda and IgM kappa M-component. According to the WHO classification, the patient was diagnosed with Waldenström macroglobulinemia (WM) after a bone morrow biopsy with 20% kappa-clonal lymphoplasmacytic cells and the presence of IgM M-components in the blood [2]. As the patient was asymptomatic, without bone marrow failure or high M-component count, watchful waiting was initiated [2].

In February 2019, the patient was admitted to the hospital with episodes of confusion, epigastric aura, and shivers. Several neurologic tests were conducted, including a head computed tomography (CT) and MRI. The CT scan showed nonspecific hypodense areas in the medial right temporal lobe with a suspicion of edema, while magnetic resonance imaging (MRI) found cerebral abnormalities in both temporal lobes. Several diagnoses, including gliomatosis cerebri and neoplasm, were possible based on the scans. Upon cytospin analysis and flow cytometry of the patient’s cerebrospinal fluid, high levels of CD19 and CD20 kappa-clonal B-cells with lymphoplasmacytic morphology were found, leading to the diagnosis of WM involvement of the central nervous system, known as BNS. The patient immediately started treatment with ibrutinib. The first month of treatment resulted in a significant reduction of clonal B-cells in the spinal tap from 180 cells/ml to 100 cells/ml estimated by flowcytometry.

In May 2019, the patient experienced confusion and fatigue. A new spinal tap showed a minor reduction of clonal B-cells (75 cells/ml), and a brain MRI confirmed progression of the patient’s disease. The treatment was changed to rituximab, methotrexate, procarbazine and vincristine (R-MPV). The patient had intolerable toxicity of R-MPV and ibrutinib was reintroduced in August 2019. The patients continued treatment with ibrutinib monotherapy and remained clinically stable for 7 months.

In March 2020 the patient developed persistent headache, and a brain MRI was performed, revealing increasing contrast enhancement in the right hemisphere (see Fig. 1). As the parenchymatic changes did not resemble those normally associated with BNS, a biopsy was performed. Surprisingly, the histology was glioblastoma, IDH wild-type, MGMT methylated. The patient was referred to the department of oncology for further treatment. Due to extensive tumor distribution in both hemispheres, radiotherapy was refrained, and the patient started treatment with TMZ as monotherapy. The patient remained clinically and radiologically stable for 6 months. In October 2020 the MRI showed mixed response, and different treatment strategies were discussed with the patient and his relatives, including continuing TMZ, starting lomustin, or awaiting the result of a new scan after a few weeks. The shared decision was to reevaluate with a new MRI after 4 weeks. Within the next month the patient had considerable symptomatic progression, which was in accordance with the follow-up MRI that showed severe progression. Due to the patient's rapidly declining condition, further treatment was abandoned. The patient died shortly after.Fig. 1 From left to right, each column illustrating the patient’s magnetic resonance imaging showing T2 weighted and T1 with gadolinium from May 2019, August 2019, and March 2020, respectively

Discussion

BNS is a rare complication of WM, characterized by clonal lymphoplasmacytic cells infiltrating the central nervous system. Patients often exhibit neurological symptoms, including balance disorders, gait abnormalities, cranial nerve deficits, cognitive impairment, and headaches [3], resembling symptoms seen in patients with GBM [4]. BNS is seen in 1–2% of patients with WM, and it is associated with great morbidity and mortality [3, 5, 6]. In addition to imaging, the gold standard for diagnosis of BNS is a spinal tap with WM cells or a brain tissue biopsy in cases where the diagnosis is uncertain [7, 8]. As our patient presented with high levels of B-cells in the cerebrospinal fluid, and responded to the initial treatment, a biopsy was not indicated.

GBM is a highly aggressive disease with a median overall survival of around 15 months [9, 10] despite multimodal treatment. It is well known that one of the treatment obstacles is the presence of the blood–brain barrier, allowing only a few small lipid soluble drugs to enter the brain parenchyma [11]. Due to the small molecular weight, ibrutinib, a covalent Bruton tyrosine kinase (BTK) inhibitor that reduces the NF-кB pathway activity, possesses the ability to pass the blood–brain barrier [8, 12, 13]. It has been widely investigated in hematological cancers and is currently recommended as first-line treatment in patients with BNS [2, 8, 14].

Due to the ability of penetrating the blood–brain barrier, the antitumoral effect of ibrutinib in glioblastomas was investigated in a laboratory setting, revealing a profound antitumor effect and induction of autophagy in GBM cells [15]. Shi et al. [16] demonstrated suppression of GBM tumor growth due to the inactivation of bone marrow and X-linked non-receptor tyrosine kinase caused by ibrutinib. To our knowledge, information on other patients with GBM treated with ibrutinib monotherapy has not been published previously. However, in the study by Lewis et al. [17], three patients developed GBM after treatment for IgM paraproteinaemic neuropathy. We are not able to evaluate whether there was a connection between development of WM and GBM in our case.

In the present case, the patient remained clinically stable for 12 months when treated with ibrutinib and R-MPV. This is unusually long for a patient with GBM, as it is a very aggressive tumor, with survival rates of only approximately 3–6 months without relevant treatment [1]. For the first 5 months, the patient received treatment with ibrutinib or R-MPV. Although procarbazine is part of the procarbazine, lomustine, vincristine (PCV) regimen often used as adjuvant treatment in patients with oligodendrogliomas, the effect in patients with GBM has been limited [18]. Therefore, we do not expect that this treatment contributed significantly to the outcome for our patient. Interestingly, the patient remained clinically stable for 7 months when ibrutinib was reintroduced. This is in line with median progression-free survival reported for patients with GBM treated with surgery, radiotherapy, and chemotherapy [1]. Therefore, this case could support the need for clinical trials for treatment with ibrutinib for patients with GBM. Currently, a study for pediatric patients with brain cancer is recruiting. [19].

We acknowledge that regular MRIs are usually used to evaluate response in patients with GBM and that an earlier MRI may have revealed progression before the patient experienced clinical worsening. As the patient did not present with symptoms, and the main goal was to keep the patient clinically stable, scans were not indicated. This was in line with the treatment and assessment strategy presented by Castillo and Treon [3].

Currently, the most clinical use of tyrosine kinase inhibitors in patients with GBM has been in a recurrent setting and with limited success [20]. Intriguingly, Wei et al. [21] investigated ibrutinib in combination with TMZ for GBM using a patient-derived xenograft mouse model, reporting that the anti-tumorigenic effect increased with a combination of ibrutinib and TMZ. A recent phase 1 study reported that daily ibrutinib in combination with TMZ and radiation is safe and feasible, indicating a clinical effect of ibrutinib, as seen in our case [22].

Conclusion

To our knowledge, this is the first patient to receive ibrutinib for GBM with a meaningful clinical outcome. Our case may support previous preclinical findings showing a therapeutic value in patients with GBM. Furthermore, as ibrutinib is an oral agent with manageable side effects, the use in an out-patient setting seems beneficial. However, no recommendations regarding ibrutinib as treatment for GBM in general can be made without further studies, including animal tests and functional studies, to reveal the true clinical effect.

Abbreviations

GBM Glioblastoma IDH-wildtype

WHO World Health Organization

TMZ Temozolomide

BNS Bing–Neel syndrome

WM Waldenström macroglobulinemia

R-MPV Rituximab, Methotrexate, Procarbazine and Vincristine

BTK Bruton tyrosine kinase

Acknowledgements

Not applicable.

Author contributions

CDG was primary manuscript author and general editor; IC was primary editor of sections regarding hematology; IBK was primary editor of sections regarding hematology and provided relevant citations; MBJ was editor with neurosurgical perspective; FSGH was editor with radiology perspective and provided images; and RHD was primary editor of sections regarding oncology and provided relevant citations. All authors approved final version of manuscript.

Funding

None.

Availability of data and materials

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Stupp R Hegi ME European organisation for research and treatment of cancer brain tumour and radiation oncology groups; national cancer institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial Lancet Oncol 2009 10 5 459 466 10.1016/S1470-2045(09)70025-7 19269895
Stupp R, Hegi ME, et al. European organisation for research and treatment of cancer brain tumour and radiation oncology groups; national cancer institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66. 10.1016/S1470-2045(09)70025-7.19269895 10.1016/S1470-2045(09)70025-7
2. Diagnostik, udredning og behandling af Lymfoplasmacystisk lymfom/ Waldenström’s macroglobulinæmi, Danske Multidisciplinære Cancer Grupper. 2020. https://www.dmcg.dk/siteassets/kliniske-retningslinjer---skabeloner-og-vejledninger/kliniske-retningslinjer-opdelt-pa-dmcg/dlg/dlg_diag_udr_beh_waldenstroms-macro_admgodk260421.pdf. Accessed on 20 Dec 2020.
3. Castillo JJ Treon SP How we manage Bing-Neel syndrome Br J Haematol 2019 187 3 277 285 10.1111/bjh.16167 31430829
Castillo JJ, Treon SP. How we manage Bing-Neel syndrome. Br J Haematol. 2019;187(3):277–85. 10.1111/bjh.16167.31430829 10.1111/bjh.16167
4. McKinnon C Nandhabalan M Glioblastoma: clinical presentation, diagnosis, and management BMJ 2021 14 374 n1560 10.1136/bmj.n1560
McKinnon C, Nandhabalan M, et al. Glioblastoma: clinical presentation, diagnosis, and management. BMJ. 2021;14(374): n1560. 10.1136/bmj.n1560.10.1136/bmj.n1560
5. Simon L Fitsiori A Lema R Bing-Neel syndrome, a rare complication of Waldenström macroglobulinemia: analysis of 44 cases and review of the literature. A study on behalf of the French Innovative Leukemia Organization (FILO) Haematologica 2015 100 12 1587 1594 10.3324/haematol.2015.133744 26385211
Simon L, Fitsiori A, Lema R, et al. Bing-Neel syndrome, a rare complication of Waldenström macroglobulinemia: analysis of 44 cases and review of the literature. A study on behalf of the French Innovative Leukemia Organization (FILO). Haematologica. 2015;100(12):1587–94. 10.3324/haematol.2015.133744.26385211 10.3324/haematol.2015.133744
6. Castillo JJ D'Sa S Lunn MP Central nervous system involvement by Waldenström macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study Br J Haematol 2016 172 5 709 715 10.1111/bjh.13883 26686858
Castillo JJ, D’Sa S, Lunn MP, et al. Central nervous system involvement by Waldenström macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study. Br J Haematol. 2016;172(5):709–15. 10.1111/bjh.13883.26686858 10.1111/bjh.13883
7. CNS-lymfom–diagnostik, behandling, rehabilitering, Dansk Lymfromgruppe. 2020. http://www.lymphoma.dk/wp-content/uploads/2020/09/DLG_CNS-Lymfom_AdmGodk180920.pdf. Accessed on 6 Feb 2020.
8. Kastritis E Leblond V ESMO guidelines committee. Waldenström's macroglobulinaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up Ann Oncol 2018 29 4 iv41 iv50 10.1093/annonc/mdy146 29982402
Kastritis E, Leblond V, et al. ESMO guidelines committee. Waldenström’s macroglobulinaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(4):iv41–50. 10.1093/annonc/mdy146. (Erratum in: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv270. Erratum in: Ann Oncol. 2019 May 1;30(5):860-862).29982402 10.1093/annonc/mdy146
9. Bjorland LS Fluge O Treatment approach and survival from glioblastoma: results from a population-based retrospective cohort study from Western Norway BMJ Open 2021 11 3 e043208 10.1136/bmjopen-2020-043208 33712524
Bjorland LS, Fluge O, et al. Treatment approach and survival from glioblastoma: results from a population-based retrospective cohort study from Western Norway. BMJ Open. 2021;11(3): e043208. 10.1136/bmjopen-2020-043208.33712524 10.1136/bmjopen-2020-043208
10. Brown NF Ottaviani D Survival outcomes and prognostic factors in glioblastoma Cancers (Basel) 2022 14 13 3161 10.3390/cancers14133161 35804940
Brown NF, Ottaviani D, et al. Survival outcomes and prognostic factors in glioblastoma. Cancers (Basel). 2022;14(13):3161. 10.3390/cancers14133161.35804940 10.3390/cancers14133161
11. Mathew EN Berry BC Delivering therapeutics to glioblastoma: overcoming biological constraints Int J Mol Sci 2022 23 3 1711 10.3390/ijms23031711 35163633
Mathew EN, Berry BC, et al. Delivering therapeutics to glioblastoma: overcoming biological constraints. Int J Mol Sci. 2022;23(3):1711. 10.3390/ijms23031711.35163633 10.3390/ijms23031711
12. Lewis KL Chin CK Manos K Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma alliance/MD Anderson Cancer Center experience Br J Haematol 2021 192 6 1049 1053 10.1111/bjh.16946 32677095
Lewis KL, Chin CK, Manos K, et al. Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma alliance/MD Anderson Cancer Center experience. Br J Haematol. 2021;192(6):1049–53. 10.1111/bjh.16946.32677095 10.1111/bjh.16946
13. Mason C Savona S Rini JN Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome Br J Haematol 2017 179 2 339 341 10.1111/bjh.14218 27409073
Mason C, Savona S, Rini JN, et al. Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome. Br J Haematol. 2017;179(2):339–41. 10.1111/bjh.14218.27409073 10.1111/bjh.14218
14. Pratt G El-Sharkawi D Kothari J Guidelines on the diagnosis and management of Waldenström macroglobulinaemia—a British society for haematology guideline Br J Haematol 2022 00 1 17 10.1111/bjh.18036
Pratt G, El-Sharkawi D, Kothari J, et al. Guidelines on the diagnosis and management of Waldenström macroglobulinaemia—a British society for haematology guideline. Br J Haematol. 2022;00:1–17. 10.1111/bjh.18036.10.1111/bjh.18036
15. Wang J Liu X Hong Y Ibrutinib, a Bruton’s tyrosine kinase inhibitor, exhibits antitumoral activity and induces autophagy in glioblastoma J Exp Clin Cancer Res 2017 36 1 96 10.1186/s13046-017-0549-6 28716053
Wang J, Liu X, Hong Y, et al. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, exhibits antitumoral activity and induces autophagy in glioblastoma. J Exp Clin Cancer Res. 2017;36(1):96. 10.1186/s13046-017-0549-6.28716053 10.1186/s13046-017-0549-6
16. Shi Y Guryanova OA Zhou W Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance Sci Transl Med. 2018 10 443 eaah6816 10.1126/scitranslmed.aah6816 29848664
Shi Y, Guryanova OA, Zhou W, et al. Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance. Sci Transl Med. 2018;10(443):eaah6816. 10.1126/scitranslmed.aah6816.29848664 10.1126/scitranslmed.aah6816
17. Lewis DM Colchester NTH Allen D Nicoll JAR Katifi HA Duncombe AS Glioblastoma, IDH-wildtype: a new association with IgM paraproteinaemic neuropathy? Case Rep Neurol. 2022 14 1 213 222 10.1159/000522239 35702059
Lewis DM, Colchester NTH, Allen D, Nicoll JAR, Katifi HA, Duncombe AS. Glioblastoma, IDH-wildtype: a new association with IgM paraproteinaemic neuropathy? Case Rep Neurol. 2022;14(1):213–22. 10.1159/000522239.35702059 10.1159/000522239
18. van den Bent MJ Brandes AA Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951 J Clin Oncol 2013 31 3 344 350 10.1200/JCO.2012.43.2229 23071237
van den Bent MJ, Brandes AA, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–50. 10.1200/JCO.2012.43.2229.23071237 10.1200/JCO.2012.43.2229
19. Kappelle AC Postma TJ PCV chemotherapy for recurrent glioblastoma multiforme Neurology 2001 56 1 118 120 10.1212/wnl.56.1.118 11148250
Kappelle AC, Postma TJ, et al. PCV chemotherapy for recurrent glioblastoma multiforme. Neurology. 2001;56(1):118–20. 10.1212/wnl.56.1.118.11148250 10.1212/wnl.56.1.118
20. TrialX. Chemo-immunotherapy using ibrutinib plus indoximod for patients with pediatric brain cancer, clinical research trial listing (medulloblastoma, primary brain tumor, glioblastoma, ependymoma) (NCT05106296 ) (trialx.com). Accessed 21 June 2024.
21. Brar HK Jose J Tyrosine kinase inhibitors for glioblastoma multiforme: challenges and opportunities for drug delivery Pharmaceutics 2022 15 1 59 10.3390/pharmaceutics15010059 36678688
Brar HK, Jose J, et al. Tyrosine kinase inhibitors for glioblastoma multiforme: challenges and opportunities for drug delivery. Pharmaceutics. 2022;15(1):59. 10.3390/pharmaceutics15010059.36678688 10.3390/pharmaceutics15010059
22. Wei L Su YK Preclinical investigation of ibrutinib, a Bruton’s kinase tyrosine (Btk) inhibitor, in suppressing glioma tumorigenesis and stem cell phenotypes Oncotarget 2016 7 43 69961 69975 10.18632/oncotarget.11572 27564106
Wei L, Su YK, et al. Preclinical investigation of ibrutinib, a Bruton’s kinase tyrosine (Btk) inhibitor, in suppressing glioma tumorigenesis and stem cell phenotypes. Oncotarget. 2016;7(43):69961–75. 10.18632/oncotarget.11572.27564106 10.18632/oncotarget.11572
23. Ahluwalia MS Phase I study of BTK inhibitor ibrutinib with temozolomide and radiation in newly-diagnosed glioblastoma (EQUILIBRIUM): final trial report J Clinic Oncol. 2023 41 2067 2067 10.1200/JCO.2023.41.16_suppl.2067
Ahluwalia MS, et al. Phase I study of BTK inhibitor ibrutinib with temozolomide and radiation in newly-diagnosed glioblastoma (EQUILIBRIUM): final trial report. J Clinic Oncol. 2023;41:2067–2067. 10.1200/JCO.2023.41.16_suppl.2067.10.1200/JCO.2023.41.16_suppl.2067
