Upadacitinib as Novel Treatment for Rheumatoid Arthritis with T-Cell Granular Lymphocytic Leukemia: A Case Report and Narrative Review

T-cell large granular lymphocyte (T-LGL) leukemia is a rare and indolent clonal disorder of LGLs, associated with rheumatoid arthritis and neutropenia. The authors present a case of a 62-year-old male with rheumatoid arthritis (RA) who was diagnosed with T-LGL leukemia, with predominant neutropenia, and a poor response to conventional treatment. Subsequently, tofacitinib (a Janus Kinase 1 and 3 inhibitor, [JAK1/3 inhibitor]) resulted in improvement of the patient’s RA symptoms and temporary improvement of the neutropenia. Ultimately, upadacitinib (a specific JAK1 inhibitor) resulted in further improvement of the neutropenia and control of his RA. To the best of our knowledge, this is the first case report of coexisting RA and LGL leukemia that was treated with upadacitinib and showed clinical improvement.

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T-Cell Large Granular Lymphocytic Leukemia: A First Case Report Diagnosed by Flow Cytometry in Vietnam

Cureus ◽

10.7759/cureus.20249 ◽

2021 ◽

Author(s):

Do T Vinh An ◽

Le Lan Anh ◽

Nguyen Tuan Tung

Keyword(s):

Flow Cytometry ◽

Case Report ◽

T Cell ◽

Lymphocytic Leukemia ◽

Large Granular Lymphocytic Leukemia ◽

First Case

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Complete remission of aggressive T-cell LGL leukemia with pentostatin therapy: first case report

Stem Cell Investigation ◽

10.21037/sci-2020-035 ◽

2020 ◽

Vol 7 ◽

pp. 24-24

Author(s):

Margaret Li Krackeler ◽

Catherine Broome ◽

Catherine Lai

Keyword(s):

Case Report ◽

T Cell ◽

Complete Remission ◽

First Case ◽

Lgl Leukemia

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FRI0136 PERIPHERAL PROTEIN BIOMARKER CHANGES FOLLOWING SELECTIVE INHIBITION OF JANUS KINASE 1 (JAK1) BY FILGOTINIB IN ADULTS WITH MODERATELY-TO-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH PRIOR INADEQUATE RESPONSE TO METHOTREXATE (FINCH1)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4704 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 650.2-651

Author(s):

P. C. Taylor ◽

E. Elboudwarej ◽

B. Downie ◽

J. Liu ◽

R. E. Hawtin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cell Migration ◽

Active Rheumatoid Arthritis ◽

Immune Cell ◽

Janus Kinase ◽

Inadequate Response ◽

Bone Biology ◽

Janus Kinase 1 ◽

Immune Cell Migration ◽

Dose Dependent

Background:Filgotinib (FIL), an oral selective Janus kinase 1 (JAK1) inhibitor has shown efficacy and safety in multiple phase 3 studies in adults with moderately-to-severely active rheumatoid arthritis (RA), including those with prior inadequate response to methotrexate (MTX) therapy (FINCH1;NCT02889796).Objectives:A longitudinal study of protein biomarkers related to JAK signaling1, bone biology2, immune cell migration2, and inflammation2was conducted to identify RA-associated markers altered by FIL vs MTX or adalimumab (ADA).Methods:FINCH1 RA patients (pts) were randomized to receive either a stable dose of MTX with placebo (PBO+MTX), ADA+MTX, and either FIL100mg+MTX or FIL200mg+MTX, once daily. Plasma, serum, and urine samples were taken from a subset of pts (~548) at baseline (BL) and weeks (wks) 4 and 12. Twenty-six pre-defined cytokines (biomarkers) were evaluated using ELISA. BL correlation between biomarkers and clinical response measures (DAS28CRP, SJC28, TJC28, CDAI, Patient Assessment and FACIT), were analyzed by Spearman Rank. Multiscale bootstrap resampling evaluated significant intra-cluster biomarker membership. Mean changes in biomarker levels from BL to wks 4 and 12 were compared between arms using PBO-adjusted estimates from a linear mixed effects model. A 5% false-discovery rate was applied for all analyses.Results:At BL, distinct biomarker-based pt clusters (CL) were identified. The strongest intra-group correlations were in bone-cartilage resorption/inflammation (CL1; Rho range 0.37–0.88) and JAK activity (CL2; Rho range 0.41–0.71). Individual BL cytokine levels were significantly associated with DAS28CRP, with unique biomarkers specific to various subcomponents of the score. Eleven biomarkers were associated with DAS28CRP, while 5, 3, and 2 were associated with CDAI, SJC28, and TJC28, respectively. The magnitude of FIL-associated treatment effects was time- and dose-dependent. Significant biomarker changes from BL were observed in FIL pts, relative to PBO+MTX pts. FIL100mg+MTX led to a significant change in 8 biomarkers by either 4 or 12 wks of treatment; FIL200mg+MTX significantly changed these and an additional 4 biomarkers by either time point. The greatest effect of FIL200mg+MTX was at 12 wks for CXCL13 (-38.4%) and IL6 (-53.7%). All treatment arms led to significant reductions in TNFα relative to PBO+MTX. FIL200mg+MTX treatment led to larger reductions of TNFα than ADA+MTX treatment at both wk4 (-24.7% vs -17.9%) and wk12 (-20.5% vs -12.2%), although the differences were not statistically significant.FIL and ADA caused differential patterns of cytokine response at either wks 4 or 12. Of 12 biomarkers with a significant FIL200mg+MTX treatment effect, there was a significantly larger reduction in TNFSF13B and CTX1 relative to ADA+MTX at 12 wks. Of 8 biomarkers with FIL100mg+MTX effects, only 2 (CXCL10 at wk 4; CXCL13 at wks 4 and 12) had significant differences from ADA+MTX. Relative either to FIL200mg+MTX or FIL100mg+MTX, and despite the same direction of effect, ADA+MTX led to a significantly larger reduction in CCL2, CXCL10, CCL4, and CXCL13.Conclusion:Compared with PBO, 12 wks of FIL treatment significantly reduced cytokines associated with JAK activity1, bone biology2, inflammation2, and immune cell migration2in MTX-IR pts. The effects were largely FIL dose-dependent; most cytokines exhibited similar effects regardless of treatment arms, but differential changes between FIL+MTX and ADA+MTX were observed, supportive of the different mechanisms of action of these therapies.References:[1]Majoros A, et al. Front Immunol. 2017;8:29[2]Brennan F, and McInnes I. J Clin Invest. 2008;118:3537-45Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Emon Elboudwarej Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Bryan Downie Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc.

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T-Cell Large Granular Lymphocytic Leukemia – Case Report

Acta Clinica Croatica ◽

10.20471/acc.2018.57.02.18 ◽

2018 ◽

Vol 57 (2) ◽

Author(s):

Sandra Kojić Katović

Keyword(s):

Case Report ◽

T Cell ◽

Lymphocytic Leukemia ◽

Large Granular Lymphocytic Leukemia

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T-Cell Large Granular Lymphocytic Leukemia with Extremely Rare Immunophenotype (CD4/CD8 Double-Positive) Followed by Multiple Myeloma Diagnosis

Case Reports in Hematology ◽

10.1155/2020/8839144 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Dina Soliman ◽

Sherin Sallam ◽

Susanna Akiki ◽

Deena Mudawi ◽

Feryal Ibrahim

Keyword(s):

Multiple Myeloma ◽

T Cells ◽

T Cell ◽

Viral Infections ◽

Cytotoxic T Cells ◽

Flow Cytometric Analysis ◽

Lymphocytic Leukemia ◽

Double Positive ◽

Large Granular Lymphocytic Leukemia ◽

First Case

T-cell large granular lymphocytic leukemia is characterized by clonal expansion of a CD3+/CD57+ subpopulation, which are typically CD8+ positive cytotoxic T- cells, and can only be diagnosed if there is a persistent, greater than 6 months, elevation of LGL in the blood (usually 2–20 × 109/L), in the absence of an identifiable cause. T-LGLL has been associated with reactive conditions such as autoimmune diseases and viral infections and has also been reported in association with hematologic and non-hematologic malignancies. We report a case of asymptomatic CD4/CD8 double-positive T-LGLL. Flow cytometry on peripheral blood revealed a subpopulation of CD4/CD8 double-positive T cells expressing CD57 and cTIA. Clonality was established by flow cytometric analysis of T-cell receptor V(â) region repertoire which showed that >70% of the cells failed to express any of the tested V(â) regions. Clonality was further confirmed by PCR with the detection of clonal TCR beta and TCR gamma gene rearrangements. Six months later, she presented with persistent lower back pain and diagnosed with IgG kappa multiple myeloma. CD4/CD8 double-positive T-large granular leukemia is the first case reported in the literature. This rare phenotype is either underreported or a truly rare clinical entity. More studies are warranted to characterize the pathogenesis and clinical characteristics of this group of patients and to further assess the relationship between multiple myeloma and T-LGLL as a cause-and-effect relationship or simply related to the time at which diagnosis has been made.

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Chronic Myeloid Leukemia in a Patient Receiving Tofacitinib: A Case Report and Literature Review

Case Reports in Rheumatology ◽

10.1155/2019/2814504 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Georgio Medawar ◽

Joseph Chahrouri ◽

Rabih Said

Keyword(s):

Rheumatoid Arthritis ◽

Case Report ◽

Myeloid Leukemia ◽

Kinase Inhibitor ◽

Janus Kinase ◽

Myelogenous Leukemia ◽

Janus Kinase Inhibitor ◽

Case Presentation ◽

Rheumatologic Diseases ◽

Refractory Rheumatoid Arthritis

Background. Tofacitinib is a new oral Janus kinase inhibitor that has shown promising clinical benefit in various rheumatologic diseases. However, many concerns related to the development of malignancies have been reported with its use. Case Presentation. A 43-year-old female patient received tofacitinib for refractory rheumatoid arthritis (RA). Two years after 5 mg bid daily dosing, the patient developed chronic myelogenous leukemia (CML), for which she received imatinib and tofacitinib was discontinued. She then remained in remission for rheumatoid arthritis and within the expected milestone outcome for her CML. Conclusion. This is the first reported case of CML after the use of tofacitinib. This event is of particular interest knowing the possible benefits tofacitinib carries in the treatment of CML demonstrated in a few studies.

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