Evidence map›Paper›PMID 40269592›Full record

ArticleNeuro-oncology2025

Phase Ib study with expansion of ibrutinib, lenalidomide, and rituximab in patients with relapsed/refractory central nervous system lymphoma.

Lauren R Schaff, Anna F Piotrowski, Elena Pentsova, Igor T Gavrilovic, Andrew Lin, Thomas J Kaley, Venissala Wongchai, Laleh Emadi-Paramkouhi, Juli Madzsar, Lillian Quinn and 14 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03703167 (Phase Ib Trial With Dose Expansion of the Bruton"s Tyrosine Kinase), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03703167 phase1completednot on this map

Phase Ib Trial With Dose Expansion of the Bruton"s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Rituximab and Lenalidomide in Patients With Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)

TypeinterventionalSponsorMemorial Sloan Kettering Cancer CenterRan2019 to 2026Enrolled25ConditionsPrimary Central Nervous System Lymphoma (PCNSL), Secondary Central Nervous System Lymphoma (SCNSL)ArmsIbrutinib, Lenalidomide, Rituximab
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Lauren R SchaffDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.ORCID 0000-0002-4664-670X
Anna F PiotrowskiDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Elena PentsovaDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.ORCID 0000-0001-5854-0251
Igor T GavrilovicDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Andrew LinDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Thomas J KaleyDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Venissala WongchaiDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Laleh Emadi-ParamkouhiDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Juli MadzsarDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Lillian QuinnDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ashley GonzalezDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Laura BreakeyDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Sarah S TangDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Joe S MendezDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Rachna MalaniDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Craig NolanDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Vaios HatzoglouDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Robert J YoungDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Lisa M DeAngelisDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Anne S ReinerDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID 0000-0002-1258-6112
Katherine S PanageasDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Jasmine H FrancisDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ingo K MellinghoffDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.
Christian GrommesDepartment of Neurology, Weill Cornell Medical College, New York, New York, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748NCI NIH HHS P30-CA008748NINDS NIH HHS NS105109-01
6 · The paper itself

Abstract

backgroundTreatment options for recurrent/refractory central nervous system (CNS) lymphoma are limited but Bruton's tyrosine kinase inhibitor ibrutinib has shown promise. To increase efficacy and reduce resistance, ibrutinib was combined with lenalidomide in a preclinical study and rituximab (R2I) in a phase Ib trial with expansion.

methodsIbrutinib 560 mg (dose level 1) or 840 mg (levels 2-4) was administered daily; lenalidomide was dosed on days 1-21 at 10 mg (level 1 + 2), 15 mg (level 3), or 20 mg (level 4) daily; rituximab 500 mg/m2 was administered every 28 days. Rituximab was given for 6 cycles, lenalidomide for 12 cycles, and ibrutinib ongoing.

results25 patients were enrolled (3 each into dose levels 1-3; 6 into level 4; and 10 into the expansion cohort at level 4). The median age was 67 years (range 41-85) and the median Eastern Cooperative Oncology Group 1 (range 0-2). Patients had a median of 2 prior regimens (range 1-5). Common adverse events were thrombocytopenia, rash, and lymphopenia. No aspergillosis or grade 5 toxicities were observed. After 12.8 months of median follow-up, 20/25 (80%) showed a response with a median time to best response of 60 days (range, 25-615). Median progression-free survival (PFS) was 4.3 months (95% CI: 2.4-not reached) with a PFS12m of 37% (95% CI: 22%-63%). Median overall survival has not been reached. Patients with rash during treatment had improved PFS (HR: 0.17, 95% CI: 0.05-0.55, P-value = .003).

conclusionsR2I was tolerated well with high response rates and a short time to best respond. Median PFS was limited but 1/3 of patients had durable responses >12 months. This trial was registered at www.clinicaltrials.gov (NCT03703167).

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsLymphomaNeoplasm Recurrence, LocalAdenineAdultAgedAged, 80 and overDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLenalidomideMaleMiddle AgedPiperidinesAdenineibrutinibLenalidomidePiperidinesPyrazolesPyrimidinesRituximabcentral nervous system lymphomaCNS lymphomaibrutiniblenalidomide

Identifiers

PMID40269592
PMCPMC12448882

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.