Il trattamento terapeutico del Linfoma di Hodgkin

Hodgkin's lymphoma is a lymphoproliferative malignant neoplasm that mostly affects young adults and is characterized by the overgrowth of a particular type of immune system cell: B lymphocytes. Studies on this disease mainly focus on classic Hodgkin's lymphoma as it represents 95% of total cases. Clinically and histologically, its features are unusual for a lymphoma in that it comprises less than 1% of the cells of the affected tissue, but most are composed of inflammatory cells, which is why the new therapeutic regimens have to do with studies related to the immunotherapy (Schnitzer, 2009; Liu & Shipp, 2017). It has led to the successful use of molecularly targeted drugs among which of one the most studied and effective is certainly bretuximab vedotin which has significantly increased progression-free survival of affected patients. It has been studied in the first-line treatment of Hodgkin's lymphoma, both in the early and advanced stages and has also played a very important role in relapsed/refractory Hodgkin's lymphoma in young adults and older adults aged 60 years and over, in cases of the impossibility of stem cell transplantation, in monotherapy rather than in combination. The improvements compared to standard combination or monotherapy chemotherapy regimens are thus highlighted (Younes et al., 2012; Connors et al., 2018; Vassilakopoulos et al., 2019). Other drugs of relevance in this pathology were the immune checkpoint inhibitors nivolumab and pembrolizumab, rituximab and histone deacetylase inhibitors (Glimelius & Diepstra, 2017; Younes et al., 2003). • Schnitzer B. Hodgkin lymphoma.Hematol Oncol Clin North Am. 2009 Aug;23(4):747-68. doi: 10.1016/j.hoc.2009.04.013.PMID: 19577168 Review. • Liu WR, Shipp MA. Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma. Blood. 2017 Nov 23;130(21):2265-2270. doi: 10.1182/blood-2017-06-781989. PMID: 29167175; PMCID: PMC5701523. • Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. Epub 2013 Nov 15. PMID: 24239220. • Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. Epub 2017 Dec 10. Erratum in: N Engl J Med. 2018 Mar 1;378(9):878. PMID: 29224502; PMCID: PMC5819601. • Vassilakopoulos TP, Chatzidimitriou C, Asimakopoulos JV, Arapaki M, Tzoras E, Angelopoulou MK, Konstantopoulos K. Immunotherapy in Hodgkin Lymphoma: Present Status and Future Strategies. Cancers (Basel). 2019 Jul 29;11(8):1071. doi: 10.3390/cancers11081071. PMID: 31362369; PMCID: PMC6721364. • Glimelius I, Diepstra A. Novel treatment concepts in Hodgkin lymphoma. J Intern Med. 2017 Mar;281(3):247-260. doi: 10.1111/joim.12582. Epub 2016 Dec 19. PMID: 27991731

Il linfoma di Hodgkin è una neoplasia maligna linfoproliferativa che colpisce in maggioranza i giovani adulti ed è caratterizzata dalla crescita eccessiva di un particolare tipo di cellule del sistema immunitario: i linfociti B. Gli studi effettuati su tale patologia si concentrano principalmente sul linfoma di Hodgkin classico in quanto rappresenta il 95% dei casi totali. Clinicamente e istologicamente le sue caratteristiche sono insolite per un linfoma in quanto comprende meno dell'1 % delle cellule del tessuto interessato, per la maggior parte da cellule infiammatorie, motivo per cui i nuovi regimi terapeutici utilizzano farmaci che sono correlati all'immunoterapia (Schnitzer, 2009; Liu & Shipp, 2017). Tra i farmaci a bersaglio molecolare uno tra i più studiati ed efficace è il bretuximab vedotin che ha aumentato la sopravvivenza libera da progressione dei pazienti affetti da linfoma di Hodgkin. Bretuximab vedotin è stato studiato nel trattamento di prima linea del linfoma di Hodgkin, sia negli stadi iniziali che avanzati della malattia e ha ricoperto un ruolo molto importante anche nel linfoma di Hodgkin recidivante/refrattario in giovani adulti e anziani con età pari o superiore ai 60 anni, nei casi di impossibilità di trapianto di cellule staminali , in monoterapia piuttosto che in combinazione (Younes et al., 2012; Connors et al., 2018; Vassilakopoulos et al., 2019). Altri farmaci di rilievo nel trattamento del linfoma di Hodgkin sono gli inibitori del checkpoint immunitario nivolumab e pembrolizumab, il rituximab e gli inibitori dell'istone deacetilasi (Glimelius & Diepstra, 2017; Younes et al., 2003). • Schnitzer B. Hodgkin lymphoma.Hematol Oncol Clin North Am. 2009 Aug;23(4):747-68. doi: 10.1016/j.hoc.2009.04.013.PMID: 19577168 Review . • Liu WR, Shipp MA. Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma. Blood. 2017 Nov 23;130(21):2265-2270. doi: 10.1182/blood-2017-06-781989. PMID: 29167175; PMCID: PMC5701523. • Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. Epub 2013 Nov 15. PMID: 24239220. • Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. Epub 2017 Dec 10. Erratum in: N Engl J Med. 2018 Mar 1;378(9):878. PMID: 29224502; PMCID: PMC5819601. • Vassilakopoulos TP, Chatzidimitriou C, Asimakopoulos JV, Arapaki M, Tzoras E, Angelopoulou MK, Konstantopoulos K. Immunotherapy in Hodgkin Lymphoma: Present Status and Future Strategies. Cancers (Basel). 2019 Jul 29;11(8):1071. doi: 10.3390/cancers11081071. PMID: 31362369; PMCID: PMC6721364. • Glimelius I, Diepstra A. Novel treatment concepts in Hodgkin lymphoma. J Intern Med. 2017 Mar;281(3):247-260. doi: 10.1111/joim.12582. Epub 2016 Dec 19. PMID: 27991731