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Newly diagnosed follicular lymphoma during pembrolizumab treatment for lung cancer

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Abstract

Malignant lymphoma developing during anti-PD-1 antibody treatment is extremely rare. A 74-year-old female was admitted with left hypochondrial pain. She was diagnosed with squamous cell carcinoma of the right upper lobe of the lung, and had undergone surgery and postoperative chemotherapy three years prior. Needle biopsy of a mediastinal lymph node revealed recurrent lung cancer (LC). Pembrolizumab (PEM) monotherapy was started as salvage treatment. Although her lymphadenopathy improved, thrombocytopenia and splenomegaly developed during treatment with nine doses of PEM. Laboratory findings included anemia, increased lactate dehydrogenase, and soluble interleukin-2 receptor levels of 6379 U/mL. Flow cytometry of peripheral blood and bone marrow showed CD20+, κ ≪  λ cell populations. IGH-BCL2 fusion was detected by fluorescence in situ hybridization in bone marrow. Positron emission tomography showed abnormal uptake in tonsils, both cervical lymph nodes, mediastinum (different location from the recurrent LC), spleen, and abdominal cavity. Follicular lymphoma (FL) grade 1/2 was histologically diagnosed by tonsillar biopsy. She achieved a complete metabolic response (CMR) after rituximab monotherapy on PEM discontinuation. Relapsed FL was diagnosed by submandibular gland biopsy four months after restarting PEM and she achieved a second CMR after rituximab-containing chemotherapy. We describe the first case of newly diagnosed FL during PEM treatment.

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Abbreviations

FL:

Follicular lymphoma

LC:

Lung cancer

PEM:

Pembrolizumab

CMR:

Complete metabolic response

PD-1:

Programmed cell death protein 1

ICIs:

Immune checkpoint inhibitors

PD-L1:

Programmed death-ligand 1

HL:

Hodgkin lymphoma

ATL:

Adult T-cell leukemia/lymphoma

FDG-PET/CT:

Fluorodeoxyglucose positron emission tomography–computed tomography

CR:

Complete response

R-CVP:

Rituximab, cyclophosphamide, vincristine, and prednisolone

CCL22:

Chemokine ligand 22

CTLs:

Cytotoxic T cells

eTregs:

Effector regulatory T cells

FL:

Follicular lymphoma

ICOS:

Inducible T-cell co-stimulator

ICOSL:

Ligand of inducible T-cell co-stimulator

IL-4:

Interleukin 4

IL-21:

Interleukin 21

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed cell death protein ligand 1

TFH :

Follicular helper T cells

TFR :

Follicular regulatory T cells

TIM3:

T cell immunoglobulin and mucin domain containing protein 3

References

  1. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–9.

    Article  Google Scholar 

  2. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–33.

    Article  CAS  Google Scholar 

  3. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.

    Article  CAS  Google Scholar 

  4. Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro JG, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394:1915–28.

    Article  CAS  Google Scholar 

  5. Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017;129:2437–42.

    Article  CAS  Google Scholar 

  6. Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018;131:68–83.

    Article  CAS  Google Scholar 

  7. Ratner L, Waldmann TA, Janakiram M, Brammer JE. Rapid progression of adult T-cell leukemia-lymphoma after PD-1 inhibitor therapy. N Engl J Med. 2018;378:1947–8.

    Article  Google Scholar 

  8. Zheng YJ, Lee A, Pincus L, Ho W, Vujic M, Ortiz-Urda S. Cutaneous CD56(+) T-cell lymphoma developing during pembrolizumab treatment for metastatic melanoma. JAAD Case Rep. 2018;4:540–2.

    Article  Google Scholar 

  9. Sengul Samanci N, Yilmaz U, Bedir S, Ozgur Yurttas N, Oruc K, Durak Sahin Z, et al. Follicular lymphoma generating in a patient with non-small cell lung cancer following nivolumab discontinuation. J Oncol Pharm Pract. 2020;26:2042–6.

    Article  Google Scholar 

  10. Champiat S, Ferrara R, Massard C, Besse B, Marabelle A, Soria JC, et al. Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat Rev Clin Oncol. 2018;15:748–62.

    Article  CAS  Google Scholar 

  11. Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, et al. PD-1(+) regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci USA. 2019;116:9999–10008.

    Article  CAS  Google Scholar 

  12. Rauch DA, Conlon KC, Janakiram M, Brammer JE, Harding JC, Ye BH, et al. Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade. Blood. 2019;134:1406–14.

    Article  Google Scholar 

  13. Kus T, Aktas G, Kalender ME, Sari I, Ulker E, Camci C. Collision tumor consisting of primary follicular lymphoma and adenocarcinoma in the cecum: a case report and literature review. Oncol Lett. 2016;11:2801–5.

    Article  Google Scholar 

  14. Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM. Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011;17:4232–44.

    Article  CAS  Google Scholar 

  15. Pangault C, Ame-Thomas P, Ruminy P, Rossille D, Caron G, Baia M, et al. Follicular lymphoma cell niche: identification of a preeminent IL-4-dependent T(FH)-B cell axis. Leukemia. 2010;24:2080–9.

    Article  CAS  Google Scholar 

  16. Ai WZ, Hou JZ, Zeiser R, Czerwinski D, Negrin RS, Levy R. Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells. Int J Cancer. 2009;124:239–44.

    Article  CAS  Google Scholar 

  17. Ame-Thomas P, Le Priol J, Yssel H, Caron G, Pangault C, Jean R, et al. Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells. Leukemia. 2012;26:1053–63.

    Article  CAS  Google Scholar 

  18. Le KS, Thibult ML, Just-Landi S, Pastor S, Gondois-Rey F, Granjeaud S, et al. Follicular B lymphomas generate regulatory T cells via the ICOS/ICOSL pathway and are susceptible to treatment by anti-ICOS/ICOSL therapy. Cancer Res. 2016;76:4648–60.

    Article  CAS  Google Scholar 

  19. Yang ZZ, Grote DM, Ziesmer SC, Xiu B, Novak AJ, Ansell SM. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 2015;5:e281.

    Article  Google Scholar 

  20. Armand P, Janssens A, Gritti G, Radford J, Timmerman J, Pinto A, et al. Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma. Blood. 2021;137:637–45.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Nagoya City West Medical Center Hematology and Oncology, Nagoya, Japan

    Yoshiaki Marumo, Takahiro Nakashima, Takaki Kikuchi, Fumiko Mori & Atsushi Inagaki

  2. Department of Clinical Oncology, Nagoya Memorial Hospital, Nagoya, Japan

    Yoshiaki Marumo

  3. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Shigeru Kusumoto, Hirokazu Komatsu & Shinsuke Iida

  4. Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Ayako Masaki & Hiroshi Inagaki

Authors
  1. Yoshiaki Marumo
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  2. Shigeru Kusumoto
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  3. Ayako Masaki
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  4. Takahiro Nakashima
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  7. Hirokazu Komatsu
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  8. Hiroshi Inagaki
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  10. Atsushi Inagaki
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Correspondence to Shigeru Kusumoto.

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Conflict of interest

Shigeru Kusumoto received personal fees from Chugai Pharmaceutical Co., Ltd., outside the submitted work. Shisuke Iida received grants and personal fees from Celgene, grants and personal fees from Janssen, grants and personal fees from Ono, grants and personal fees from Takeda, grants and personal fees from Bristol-Myers Squibb, grants from Chugai, grants from Kyowa Kirin, grants and personal fees from Sanofi, grants from Abbvie, grants and personal fees from Daiichi Sankyo, outside the submitted work.

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Marumo, Y., Kusumoto, S., Masaki, A. et al. Newly diagnosed follicular lymphoma during pembrolizumab treatment for lung cancer. Int J Hematol 114, 280–285 (2021). https://doi.org/10.1007/s12185-021-03135-5

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  • DOI: https://doi.org/10.1007/s12185-021-03135-5

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