The evidence to date on umbralisib for the treatment of refractory marginal zone lymphoma and follicular lymphoma

References

• Teras LR, DeSantis CE, and Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;66(6):443–459. 2016.
   PubMed Web of Science ®Google Scholar
• Solal-Céligny P, Lepage E, Brousse N, et al. Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the groupe d’etude des lymphames folliculaires 86 trial. J clin oncol. 1998;16(7):2332–2338.
   PubMed Web of Science ®Google Scholar
• Marcus R, Davies A, Ando K, et al. Obinutuzumab for the first-line treatment of Follicular Lymphoma. N Engl J Med. 2017;377(14):1331–1344.
   PubMed Web of Science ®Google Scholar
• Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377(9759):42–51.
   PubMed Web of Science ®Google Scholar
• Maurer MJ, Bachy E, Ghesquières H, et al. Early event status informs subsequent outcome in newly diagnosed follicular lymphoma. Am J Hematol. 2016;91(11):1096–1101.
   PubMed Web of Science ®Google Scholar
• AK G, SJ S, NH F, et al. Ibrutinib as treatment for patients with Relapsed/Refractory Follicular Lymphoma: results from the open-label, multicenter, phase II dawn study. J Clin Oncol. 2018;36(23):2405–2412.
   PubMed Web of Science ®Google Scholar
• C C, B M, D KL, et al. Early relapse of follicular lymphoma after rituximab plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J Clin Oncol. 2015;33(23):2516–2522.
   PubMed Web of Science ®Google Scholar
• Solal-Céligny P S, Pascal R, Colombat P, et al. Follicular lymphoma international prognostic index. Blood. 2004;104(5):1258–1265.
   PubMed Web of Science ®Google Scholar
• Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129(7):1261–1274.
   PubMed Web of Science ®Google Scholar
• Vanhaesebroeck B, Perry MWD, Brown JR, et al. PI3K inhibitors are finally coming of age. Nature Reviews. Drug Discovery. 2021;20(10):741–769.
   PubMed Web of Science ®Google Scholar
• Fruman DA, Chiu H, Hopkins BD, et al. The PI3K Pathway in Human Disease. Cell. 2017;170(4):605–635.
   PubMed Web of Science ®Google Scholar
• Flinn IW, O’Brien S, Kahl B, et al. Duvelisib, a novel oral dual inhibitor of PI3K-d,g, is clinically active in advanced hematologic malignancies. Blood. 2018;131(8):877–887.
   PubMed Web of Science ®Google Scholar
• Bw M, P D, de C RA, et al. FDA approval: idelalisib monotherapy for the treatment of patients with follicular lymphoma and small lymphocytic lymphoma. J Clin Oncol. 2015;21(7):1525–1529.
   Google Scholar
• Gopal A, Kahl B, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–1018.
   PubMed Web of Science ®Google Scholar
• Dreyling S, Santoro, Mollica A, et al. Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in relapsed or refractory Indolent Lymphoma. J Clin Oncol. 2017;35(35):3898–3905.
   PubMed Web of Science ®Google Scholar
• Dreyling M, Santoro A, Mollica L, et al. Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study. Am J Hematol. 2020;95(4):362–371.
   PubMed Web of Science ®Google Scholar
• Flinn IW, Miller CB, Ardeshna KM, et al. DYNAMO: a Phase II study of duvelisib (IPI-145) in patients with refractory indolent non-hodgkin lymphoma. In: J Clin Oncol 37; 2019:912–922.
   PubMed Web of Science ®Google Scholar
• Zelenetz AD, Gordon LI, Abramson JS, et al. NCCN guidelines insights: b-Cell Lymphomas, version 3.2019. J Natl Compr Cancer Network. 2019;17(6):650–661.
   PubMed Web of Science ®Google Scholar
• Lampson BL, Kasar SN, Matos TR, et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood. 2016;128(2):195–203.
   PubMed Web of Science ®Google Scholar
• Wagner-Johnston ND, Sharman J, Furman RR, et al. Idelalisib immune-related toxicity is associated with improved treatment response. Leuk Lymphoma. 2021;62(12):2915–2920.
   PubMed Web of Science ®Google Scholar
• André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA -mutated, hormone receptor–positive advanced Breast Cancer. N Engl J Med. 2019;380(20):1929–1940.
   PubMed Web of Science ®Google Scholar
• Idelalisib [package insert]. Foster City CA: Gilead Sciences, Inc; 2014. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206545lbl.pdf
   Google Scholar
• Copanlisib [package insert]. Hippany NJ: Bayer HealthCare Pharmaceutical, Inc; 2017. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209936s000lbl.pdf
   Google Scholar
• Duvelisib [package insert]. Needham MA: Verastem, Inc; 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211155s000lbl.pdf
   Google Scholar
• Burris HA, Flinn IW, Patel MR, et al. Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol. 2018;19(4):486–496.
   PubMed Web of Science ®Google Scholar
• Deng C, Lipstein M, Scotto L, et al. Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kδ and CK1ε in hematological malignancies. Blood. 2017;129(1):88–99.
   PubMed Web of Science ®Google Scholar
• Janovská P, Normant E, Miskin H, et al. Targeting casein kinase 1 (Ck1) in hematological cancers. Int J Mol Sci. 2020;21(23):1–19.
   Web of Science ®Google Scholar
• Fowler NH, Samaniego F, Jurczak W, et al. Umbralisib, a Dual PI3Kδ/CK1ε inhibitor in patients with relapsed or refractory indolent Lymphoma. J Clin Oncol. 2021;39(15):1609–1618.
   PubMed Web of Science ®Google Scholar
• Noy A, de Vos S, Thieblemont C, et al. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017;129(16):2224–2232.
   PubMed Web of Science ®Google Scholar
• Davids M, O’Connor OA, and Jurczak, et al. Integrated safety analysis of umbralisib, adual PI3Kδ/CK1ε inhibitor, in relapsed/refractory lymphoid malignancies. Blood. 2021; 5(23):5332–5343.
   Web of Science ®Google Scholar
• Umbralisib [package insert]. Edison NJ: TG Therapeutics, Inc; 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf
   Google Scholar
• Casulo C, Byrtek M, Dawson K, et al. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: an Analysis From the National LymphoCare Study. J Clin Oncol. 2015;33(23):2516–2522.
   PubMed Web of Science ®Google Scholar
• Conconi A, Thieblemont C, Cascione L, et al. Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment. Haematologica. 2020;105(11):2592–2597.
   PubMed Web of Science ®Google Scholar
• Casulo C, Barr PM. How I treat early-relapsing follicular lymphoma. Blood. 2019;133(14):1540–1547.
   PubMed Web of Science ®Google Scholar
• Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: a Phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. In: J Clin Oncol 37; 2019:1188–1199.
   PubMed Web of Science ®Google Scholar
• Morschhauser F, Fowler NH, Feugier P, et al. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018;379(10):934–947.
   PubMed Web of Science ®Google Scholar
• Fung M, Jacobsen E, Freedman A, et al. increased risk of infectious complications in older patients with indolent Non-Hodgkin Lymphoma Exposed to Bendamustine. Clinl Infect Dis. 2019;68(2):247–255.
   PubMed Web of Science ®Google Scholar
• Klepin HD. Ready for prime time: role for geriatric assessment to improve quality of care in hematology practice. Blood. 2019;134(23):2005–2012.
   PubMed Web of Science ®Google Scholar
• Schuster SJ. Bispecific antibodies for the treatment of lymphomas: promises and challenges. Hematol Oncol. 2021;39(S1):113–116.
   PubMed Web of Science ®Google Scholar
• Chen LS, Bose P, Cruz ND, et al. A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia. Blood. 2018;132(21):2249–2259.
   PubMed Web of Science ®Google Scholar
• Levy I, Lavi A, Zimran E, et al. COVID-19 among patients with hematological malignancies: a national Israeli retrospective analysis with special emphasis on treatment and outcome. Leukemia Lymphoma. 2021;62:3384–3393.
   PubMed Web of Science ®Google Scholar
• Jazieh AR, Chan SL, Curigliano G, et al. Delivering Cancer Care During the COVID-19 pandemic: recommendations and lessons learned from ASCO global webinars. JCO Global Oncol. 2020;6:1461–1471.
   PubMedGoogle Scholar