Current Opinion on Pixantrone in the Treatment of Non-Hodgkin B-Cell Lymphoma

References

• Sarkozy C, Sehn LH. New drugs for the management of relapsed or refractory diffuse large B-cell lymphoma. Ann Lymphoma. 2019;3:10. doi:10.21037/aol.2019.09.01
   Google Scholar
• Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematol Am Soc Hematol Educ Progr. 2011;2011:498–505. doi:10.1182/asheducation-2011.1.498
   PubMed Web of Science ®Google Scholar
• Gregoric B, Zadnik V, Jezersek Novakovic B. The diffuse large B-cell lymphoma – where do we stand now in everyday clinical practice. Radiol Oncol. 2012;46(2):153–159. doi:10.2478/v10019-012-0002-6
   PubMed Web of Science ®Google Scholar
• Horvat M, Zadnik V, Južnič Šetina T, et al. Diffuse large B-cell lymphoma: 10 years’ real-world clinical experience with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone. Oncol Lett. 2018;15(3):3602–3609. doi:10.3892/ol.2018.7774
   PubMed Web of Science ®Google Scholar
• Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–1808. doi:10.1182/blood-2017-03-769620
   PubMed Web of Science ®Google Scholar
• Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333(23):1540–1545. doi:10.1056/NEJM199512073332305
   PubMed Web of Science ®Google Scholar
• Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl5):V116–V125. doi:10.1093/annonc/mdv304
   PubMed Web of Science ®Google Scholar
• Nabhan C, Klink A, Lee CH, Laney JR, Yang Y, Purdum AG. Overall survival (OS) and transplantation (ASCT) utilization in real-world patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) [ASCO abstract]. J Clin Oncol. 2018;36(15 Suppl 1):7545. doi:10.1200/JCO.2018.36.15_suppl.7545
   Web of Science ®Google Scholar
• Keating GM. Pixantrone: a review in relapsed or refractory aggressive non-hodgkin’s lymphoma. Drugs. 2016;76(16):1579–1586. doi:10.1007/s40265-016-0650-8
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Pixuvri (pixantrone dimaleate): summary of product characteristics [document on the Internet]; 2016. Available from: https://www.ema.europa.eu/en/documents/product-information/pixuvri-epar-product-information_en.pdf. Accessed October 10, 2020.
   Google Scholar
• Pettengell R, Coiffier B, Narayanan G, et al. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a Phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012;13(7):696–706. doi:10.1016/S1470-2045(12)70212-7
   PubMed Web of Science ®Google Scholar
• Belada D, Georgiev P, Dakhil S, et al. Pixantrone-rituximab versus gemcitabine-rituximab in relapsed/refractory aggressive non-Hodgkin lymphoma. Future Oncol. 2016;12(15):1759–1768. doi:10.2217/fon-2016-0137
   PubMed Web of Science ®Google Scholar
• Salles GA, Jurczak W, Andorsky DJ, et al. Results of a phase 3 randomised multicenter study comparing pixantrone + rituximab with gemcitabine + rituximab in patients with relapsed aggressive B-cell non-hodgkin lymphoma not eligible for stem cell transplantation [ASH abstract]. Blood. 2018;132(Suppl1):4189. doi:10.1182/blood-2018-99-112455
   Web of Science ®Google Scholar
• Pettengell R, Długosz-Danecka M, Andorsky D, et al. Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306). Br J Haematol. 2020;188(2):240–248. doi:10.1111/bjh.16255
   PubMed Web of Science ®Google Scholar
• Eyre TA, Linton KM, Rohman P, et al. Results of a multicentre UK-wide retrospective study evaluating the efficacy of pixantrone in relapsed, refractory diffuse large B cell lymphoma. Br J Haematol. 2016;173(6):896–904. doi:10.1111/bjh.14021
   PubMed Web of Science ®Google Scholar
• Sancho J-M, Navarro B, Soler Campos JA, et al. Efficacy and safety of pixantrone for the treatment of multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas. Eur J Haematol. 2020;104(5):499–508. doi:10.1111/ejh.13392
   PubMed Web of Science ®Google Scholar
• Novakovic A, Boltezar L, Jezersek novakovic B. Limited efficacy of pixantrone in refractory diffuse large B-cell lymphoma. Oncol Lett. 2020;19(3):2028–2034. doi:10.3892/ol.2020.11288
   PubMed Web of Science ®Google Scholar
• Schuster SJ, Svoboda J, Chong EA, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377(26):2545–2554. doi:10.1056/NEJMoa1708566
   PubMed Web of Science ®Google Scholar
• Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45–56. doi:10.1056/NEJMoa1804980
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–2544. doi:10.1056/NEJMoa1707447
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy – assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62. doi:10.1038/nrclinonc.2017.148
   PubMed Web of Science ®Google Scholar
• Hernandez I, Prasad V, Gellad WF. Total costs of chimeric antigen receptor T-cell immunotherapy. JAMA Oncol. 2018;4(7):994–996. doi:10.1001/jamaoncol.2018.0977
   PubMed Web of Science ®Google Scholar
• Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(2):155–165. doi:10.1200/JCO.19.00172
   PubMed Web of Science ®Google Scholar
• Maddocks KJ, Duell J, González Barca E, et al. Update of the single-arm phase II L-MIND study of MOR208 + lenalidomide (LEN) in relapsed/refractory diffuse large B-cell lymphoma (R-R DLBCL): response rates in patient subgroups with poor prognosis [ASCO abstract]. J Clin Oncol. 2019;37(15Suppl 1):7521. doi:10.1200/JCO.2019.37.15_suppl.7521
   Google Scholar
• Karyopharm Therapeutics Inc.. Karyopharm announces FDA approval of XPOVIO® (selinexor) for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) [press release on the Internet]; 2020. Available from: https://investors.karyopharm.com/2020-06-22-Karyopharm-Announces-FDA-Approval-of-XPOVIO-R-selinexor-for-the-Treatment-of-Patients-with-Relapsed-or-Refractory-Diffuse-Large-B-cell-Lymphoma-DLBCL. Accessed January 22, 2021.
   Google Scholar
• Volpetti S, Zaja F, Fanin R. Pixantrone for the treatment of adult patients with relapsed or refractory aggressive non-Hodgkin B-cell lymphomas. Onco Targets Ther. 2014;7:865–872. doi:10.2147/OTT.S34055
   PubMed Web of Science ®Google Scholar
• Sawyer DB. Anthracyclines and heart failure. N Engl J Med. 2013;368(12):1154–1156. doi:10.1056/NEJMcibr1214975
   PubMed Web of Science ®Google Scholar
• Hasinoff BB, Wu X, Patel D, Kanagasabai R, Karmahapatra S, Yalowich JC. Mechanisms of action and reduced cardiotoxicity of pixantrone; a topoisomerase II targeting agent with cellular selectivity for the topoisomerase IIα isoform. J Pharmacol Exp Ther. 2016;356(2):397–409. doi:10.1124/jpet.115.228650
   PubMed Web of Science ®Google Scholar
• Menna P, Salvatorelli E, Minotti G. Rethinking drugs from chemistry to therapeutic opportunities: pixantrone beyond anthracyclines. Chem Res Toxicol. 2016;29(8):1270–1278. doi:10.1021/acs.chemrestox.6b00190
   PubMed Web of Science ®Google Scholar
• Salvatorelli E, Menna P, Paz OG, et al. The novel anthracenedione, pixantrone, lacks redox activity and inhibits doxorubicinol formation in human myocardium: insight to explain the cardiac safety of pixantrone in doxorubicin-treated patients. J Pharmacol Exp Ther. 2013;344(2):467–478. doi:10.1124/jpet.112.200568
   PubMed Web of Science ®Google Scholar
• Pettengell R, Kaur J. Pixantrone dimaleate for treating non-Hodgkin’s lymphoma. Expert Opin Orphan Drugs. 2015;3(6):747–757. doi:10.1517/21678707.2015.1042454
   Web of Science ®Google Scholar
• Evison BJ, Mansour OC, Menta E, Phillips DR, Cutts SM. Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent. Nucleic Acids Res. 2007;35(11):3581–3589. doi:10.1093/nar/gkm285
   PubMed Web of Science ®Google Scholar
• Beeharry N, Di Rora AGL, Smith MR, Yen TJ. Pixantrone induces cell death through mitotic perturbations and subsequent aberrant cell divisions. Cancer Biol Ther. 2015;16(9):1397–1406. doi:10.1080/15384047.2015.1070979
   PubMed Web of Science ®Google Scholar
• Beggiolin G, Crippa L, Menta E, et al. Bbr 2778, an aza-anthracenedione endowed with preclinical anticancer activity and lack of delayed cardiotoxicity. Tumori. 2001;87(6):407–416. doi:10.1177/030089160108700611
   PubMed Web of Science ®Google Scholar
• Cavalletti E, Crippa L, Mainardi P, et al. Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone. Invest New Drugs. 2007;25(3):187–195. doi:10.1007/s10637-007-9037-8
   PubMed Web of Science ®Google Scholar
• Longo M, Della Torre P, Allievi C, Morisetti A, Al-Fayoumi S, Singer JW. Tolerability and toxicological profile of pixantrone (Pixuvri®) in juvenile mice. Comparative study with doxorubicin. Reprod Toxicol. 2014;46:20–30. doi:10.1016/j.reprotox.2014.02.006
   PubMed Web of Science ®Google Scholar
• Borchmann P, Schnell R, Knippertz R, et al. Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin’s lymphoma. Ann Oncol off J Eur Soc Med Oncol. 2001;12(5):661–667. doi:10.1023/a:1011139016294
   PubMed Web of Science ®Google Scholar
• Faivre S, Raymond E, Boige V, et al. A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. Clin Cancer Res. 2001;7(1):43–50.
   PubMed Web of Science ®Google Scholar
• Dawson LK, Jodrell DI, Bowman A, et al. A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. Eur J Cancer. 2000;36(18):2353–2359. doi:10.1016/s0959-8049(00)00342-7
   PubMed Web of Science ®Google Scholar
• Borchmann P, Morschhauser F, Parry A, et al. Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin’s lymphomas. Haematologica. 2003;88(8):888–894.
   PubMed Web of Science ®Google Scholar
• Pettengell R, Sebban C, Zinzani PL, et al. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016;174(5):692–699. doi:10.1111/bjh.14101
   PubMed Web of Science ®Google Scholar
• Pettengell R, Coiffier B, Egorov A, Singer J, Sivcheva L. Long-term response and remission with pixantrone in patients with relapsed or refractory aggressive non-hodgkin lymphoma: post-hoc analysis of the multicenter, Open-label, randomized PIX301 trial. Clin Drug Investig. 2018;38(6):527–533. doi:10.1007/s40261-018-0635-3
   PubMed Web of Science ®Google Scholar
• Herbrecht R, Cernohous P, Engert A, et al. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol off J Eur Soc Med Oncol. 2013;24(10):2618–2623. doi:10.1093/annonc/mdt289
   PubMed Web of Science ®Google Scholar
• University of Freiburg. R-CPOP as first-line therapy for elderly patients with DLBCL and for patients with limited cardiac function with DLBCL. Available from: https://www.clinicaltrialsregister.eu/. EudraCT number: 2014–005069-60. Accessed October 10, 2020.
   Google Scholar
• Marks R, Strüßmann T, Krohn U, Duyster J, Finke J, Fritsch K. Feasibility of pixantrone containing R-CPOP as first-line treatment for patients with aggressive B cell lymphoma with congestive heart failure or at risk of anthracycline induced cardiotoxicity [EHA abstract]. HemaSphere. 2018;2(Suppl 1):813.
   Google Scholar
• Borchmann P, Herbrecht R, Wilhelm M, et al. Phase I/II study of pixantrone in combination with cyclophosphamide, vincristine, and prednisone in patients with relapsed aggressive non-Hodgkin lymphoma. Leuk Lymphoma. 2011;52(4):620–628. doi:10.3109/10428194.2010.546016
   PubMed Web of Science ®Google Scholar
• d’Amore F, Joergensen J, Sillesen IB, et al. Preliminary clinical experience on the efficacy and feasibility of a new combination regimen consisting of pixantrone, etoposide, and bendamustine with or without the addition of rituximab in patients with relapsed/refractory aggressive non-Hodgkin lymphomas [ASH abstract]. Blood. 2014;124(8):5435. doi:10.1182/blood.V124.21.5435.5435
   Web of Science ®Google Scholar
• Clausen MR, Leppa S, Brown PN, et al. The combination of pixantrone, etoposide, bendamustine and, in CD20+ tumors, rituximab (PREBEN) shows promising feasibility/efficacy in heavily pre-treated aggressive lymphomas of B- and T-cell phenotype – results of the pre-trial experience leading to a Nordic Phase 1/2 study (the PREBEN trial) [ASH abstract]. Blood. 2016;128(22):1782. doi:10.1182/blood.V128.22.1782.1782
   PubMed Web of Science ®Google Scholar
• Barrenetxea Lekue C, Alonso Caballero C, Hernández Vázquez L, et al. Preben: pixantrone, rituximab, etoposide and bendamustine, Spanish experience in diffuse large B-cell lymphoma treatment [ASH abstract]. Blood. 2017;130(Suppl 1):5235.
   Google Scholar
• Aarhus University Hospital. Phase 1/2 study of the combination of pixantrone, etoposide, bendamustine and, in CD20 positive tumors, rituximab in patients with relapsed aggressive non-hodgkin lymphomas of B- or T-cell phenotype - the P[R]EBEN study. Available from: https://www.clinicaltrialsregister.eu/. EudraCT No. 2015-000758-39. Accessed October 10, 2020.
   Google Scholar
• Jørgensen J, Leppä S, Relander T, et al. A phase Ib, open label, multicenter trial of pixantrone, etoposide, bendamustine and, in CD20-positive tumors, rituximab (PREBEN) in relapsed aggressive lymphomas of B- or T-cell phenotype [EHA abstract]. HemaSphere. 2018;2(Suppl 1):808.
   Google Scholar
• d’Amore F, Leppä S, Larsen TS, et al. A phase 1/2 study of pixantrone, etoposide, bendamustine and, in CD20+ tumors, rituximab in patients with relapsed aggressive B- or T-cell lymphomas—the P[R]EBEN study [ICML abstract]. Hematol Oncol. 2017;35(Suppl2):423–424. doi:10.1002/hon.2440_7
   Google Scholar
• Długosz-Danecka M, Hus I, Puła B, et al. Pixantrone, etoposide, bendamustine, rituximab (P[R]EBEN) as an effective salvage regimen for relapsed/refractory aggressive non-Hodgkin lymphoma-Polish Lymphoma Research Group real-life analysis. Pharmacol Rep. 2019;71(3):473–477. doi:10.1016/j.pharep.2019.02.001
   PubMed Web of Science ®Google Scholar
• Lim S-T, Fayad L, Tulpule A, et al. A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin’s lymphoma. Leuk Lymphoma. 2007;48(2):374–380. doi:10.1080/10428190601060496
   PubMed Web of Science ®Google Scholar
• Santoro A, Voglova J, Gabrail N, et al. Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL) [ASCO abstract]. J Clin Oncol. 2006;24(18Suppl 1):7578. doi:10.1200/jco.2006.24.18_suppl.7578
   Google Scholar
• Srokowski TP, Liebmann JE, Modiano MR, et al. Pixantrone dimaleate in combination with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: phase 1 study with a dose-expansion cohort. Cancer. 2011;117(22):5067–5073. doi:10.1002/cncr.26121
   PubMed Web of Science ®Google Scholar
• Boyle EM, Morschhauser F. Pixantrone: a novel anthracycline-like drug for the treatment of non-Hodgkin lymphoma. Expert Opin Drug Saf. 2015;14(4):601–607. doi:10.1517/14740338.2015.1010505
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Pixuvri (pixantrone): CHMP assessment report [document on the Internet]. London: Committee for Medicinal Products for Human Use (CHMP); 2012. Available from: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf. Accessed October 10, 2020.
   Google Scholar
• Papadatos-Pastos D, Pettengell R. Pixantrone: merging safety with efficacy. Expert Rev Hematol. 2013;6(1):25–33. doi:10.1586/ehm.12.61
   PubMed Web of Science ®Google Scholar
• Barrenetxea Lekue C, Grasso Cicala S, Leppä S, et al. Pixantrone beyond monotherapy: a review. Ann Hematol. 2019;98(9):2025–2033. doi:10.1007/s00277-019-03749-0
   PubMed Web of Science ®Google Scholar
• Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol off J Eur Soc Med Oncol. 2020;31(2):171–190. doi:10.1016/j.annonc.2019.10.023
   PubMed Web of Science ®Google Scholar
• Borchmann P, Tam CS, Jäger U, et al. An updated analysis of JULIET, a global pivotal Phase 2 trial of tisagenlecleucel in adult patients with relapsed or refractory diffuse large B-cell lymphoma [EHA abstract]. HemaSphere. 2018;2(Suppl 1):347.
   Google Scholar
• Morschhauser F, Flinn IW, Advani R, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019;6(5):e254–e265. doi:10.1016/S2352-3026(19)30026-2
   PubMed Web of Science ®Google Scholar
• Eyre TA. Another disappointment in treating relapsed, refractory high-risk aggressive B-cell lymphomas. Br J Haematol. 2020;188(2):202–204. doi:10.1111/bjh.16259
   PubMed Web of Science ®Google Scholar
• Fields PA, Townsend W, Webb A, et al. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. J Clin Oncol. 2014;32(4):282–287. doi:10.1200/JCO.2013.49.7586
   PubMed Web of Science ®Google Scholar
• Luminari S, Viel E, Ferreri AJM, et al. Nonpegylated liposomal doxorubicin combination regimen in patients with diffuse large B-cell lymphoma and cardiac comorbidity. Results of the HEART01 phase II trial conducted by the Fondazione Italiana Linfomi. Hematol Oncol. 2018;36(1):68–75. doi:10.1002/hon.2425
   PubMed Web of Science ®Google Scholar
• Shen Q-D, Zhu H-Y, Wang L, et al. Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial. Lancet Haematol. 2018;5(6):e261–e269. doi:10.1016/S2352-3026(18)30054-1
   PubMed Web of Science ®Google Scholar