Skip to main content
Erschienen in:

12.08.2024 | Rapid Communication

Pathological landscape of tumor flare reaction to epcoritamab treatment

verfasst von: Osamu Imataki, Makiko Uemura, Haruyuki Fujita, Norimitsu Kadowaki

Erschienen in: International Journal of Hematology | Ausgabe 4/2024

Einloggen, um Zugang zu erhalten

Abstract

Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed “tumor pseudoprogression.” The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. The third injection, scheduled for day 15, was delayed by 1 week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20+ large atypical lymphocytes forming residual nodules, encircled by CD4+ and CD8+ lymphocytes, with a predominance of CD8+ T cells over CD4+ T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.
Literatur
1.
Zurück zum Zitat Taleb BA. Tumour flare reaction in cancer treatments: a comprehensive literature review. Anticancer Drugs. 2019;30:953–8.CrossRef Taleb BA. Tumour flare reaction in cancer treatments: a comprehensive literature review. Anticancer Drugs. 2019;30:953–8.CrossRef
2.
Zurück zum Zitat Ramos-Casals M, Brahmer JR, Callahan MK, Flores-Chávez A, Keegan N, Khamashta MA, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers. 2020;6:38.CrossRefPubMedPubMedCentral Ramos-Casals M, Brahmer JR, Callahan MK, Flores-Chávez A, Keegan N, Khamashta MA, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers. 2020;6:38.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Billan S, Kaidar-Person O, Gil Z. Treatment after progression in the era of immunotherapy. Lancet Oncol. 2020;21:e463–76.CrossRefPubMed Billan S, Kaidar-Person O, Gil Z. Treatment after progression in the era of immunotherapy. Lancet Oncol. 2020;21:e463–76.CrossRefPubMed
4.
Zurück zum Zitat Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, et al. Management of immunotherapy-related toxicities. J Natl Compr Canc Netw. 2019;17:255–89.CrossRefPubMed Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, et al. Management of immunotherapy-related toxicities. J Natl Compr Canc Netw. 2019;17:255–89.CrossRefPubMed
5.
Zurück zum Zitat Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–38.CrossRefPubMed Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–38.CrossRefPubMed
6.
Zurück zum Zitat Crombie JL, Graff T, Falchi L, Karimi YH, Bannerji R, Nastoupil LJ, et al. Consensus recommendations on the management of toxicity associated with CD3 × CD20 bispecific antibody therapy. Blood. 2024;143:1565–75.CrossRefPubMed Crombie JL, Graff T, Falchi L, Karimi YH, Bannerji R, Nastoupil LJ, et al. Consensus recommendations on the management of toxicity associated with CD3 × CD20 bispecific antibody therapy. Blood. 2024;143:1565–75.CrossRefPubMed
7.
Zurück zum Zitat de Miguel M, Calvo E. Clinical challenges of immune checkpoint inhibitors. Cancer Cell. 2020;38:326–33.CrossRefPubMed de Miguel M, Calvo E. Clinical challenges of immune checkpoint inhibitors. Cancer Cell. 2020;38:326–33.CrossRefPubMed
8.
Zurück zum Zitat Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3 × CD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a Phase I/II trial. J Clin Oncol. 2023;41:2238–47.CrossRefPubMed Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3 × CD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a Phase I/II trial. J Clin Oncol. 2023;41:2238–47.CrossRefPubMed
9.
Zurück zum Zitat Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021;398:1157–69.CrossRefPubMed Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021;398:1157–69.CrossRefPubMed
10.
Zurück zum Zitat Izutsu K, Kumode T, Yuda J, Nagai H, Mishima Y, Suehiro Y, et al. Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. Cancer Sci. 2023;114:4643–53.CrossRefPubMedPubMedCentral Izutsu K, Kumode T, Yuda J, Nagai H, Mishima Y, Suehiro Y, et al. Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. Cancer Sci. 2023;114:4643–53.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol. 2021;39:1959–70.CrossRefPubMedPubMedCentral Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol. 2021;39:1959–70.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Sortais C, Cordeil S, Bourbon E, Idlhaj M, Ferrant E, Safar V, et al. Flare-up phenomenon or pseudoprogression after CAR T-cell infusion in non-Hodgkin aggressive lymphomas. Leuk Lymphoma. 2023;64:707–11.CrossRefPubMed Sortais C, Cordeil S, Bourbon E, Idlhaj M, Ferrant E, Safar V, et al. Flare-up phenomenon or pseudoprogression after CAR T-cell infusion in non-Hodgkin aggressive lymphomas. Leuk Lymphoma. 2023;64:707–11.CrossRefPubMed
13.
Zurück zum Zitat Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2022;33:259–75.CrossRefPubMed Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2022;33:259–75.CrossRefPubMed
14.
Zurück zum Zitat Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128:2489–96.CrossRefPubMed Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128:2489–96.CrossRefPubMed
15.
Zurück zum Zitat Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–20.CrossRefPubMed Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–20.CrossRefPubMed
16.
Zurück zum Zitat Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16:356–71.CrossRefPubMed Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16:356–71.CrossRefPubMed
Metadaten
Titel
Pathological landscape of tumor flare reaction to epcoritamab treatment
verfasst von
Osamu Imataki
Makiko Uemura
Haruyuki Fujita
Norimitsu Kadowaki
Publikationsdatum
12.08.2024
Verlag
Springer Nature Singapore
Erschienen in
International Journal of Hematology / Ausgabe 4/2024
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-024-03833-w

Neu im Fachgebiet Onkologie

Fünf Faktoren sagen Lymphödeme nach Brustkrebs voraus

Ob nach der operativen Behandlung von Brustkrebs ein Lymphödem droht, lässt sich anhand eines Risikomodells abschätzen, das auf fünf leicht verfügbaren klinischen Parametern beruht.

Genügt die biparametrische MRT für die Prostatadiagnostik?

Die multiparametrische Magnetresonanztomografie hat einen festen Platz im Screening auf klinisch signifikante Prostatakarzinome. Ob auch ein biparametrisches Vorgehen ausreicht, ist in einer Metaanalyse untersucht worden.

Metastasiertes CRC: besser Checkpointhemmer im Doppelpack!

Die Kombination von Nivolumab plus Ipilimumab ist beim metastasierten Kolorektalkarzinom mit MSI-H- oder dMMR klar im Vorteil gegenüber einer Nivolumab-Monotherapie: Das Progressionsrisiko war damit in einer Phase-3-Studie um 38% reduziert.

Große Trinkmengen bei Blasentumoren möglicherweise von Nachteil

Beim nicht-muskelinvasiven Blasenkrebs scheint eine hohe Flüssigkeitszufuhr keinen schützenden Effekt in Bezug auf das Risiko eines Rezidivs oder einer Krankheitsprogression zu haben. Eine niederländische Studie legt sogar nahe, dass große Trinkmengen das Fortschreiten der Erkrankung begünstigen könnten.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.