New Targeted Therapies

Led a multi-institutional trial demonstrating the efficacy of imatinib mesylate (Gleevec) for producing long-term complete remissions in chronic myelocytic leukemia, leading to FDA approval. This was the first highly successful drug proving the concept of targeted therapy.

Kantarjian H, Talpaz M, O’Brien S, Smith TL, Giles F, Faderl S, Thomas DA, Garcia-Manero G, Issa JP, Andreeff M, Kornblau S, Koller C, Beran M, Keating M, Rios MB, Shan J, Resta D, Capdeville R, Hayes K, Albitar M, Freireich E, Cortes J. Imatinib mesylate for Philadelphia-chromosome-positive, chronic-phase myeloid leukemia after failure of Interferon-α: Follow-up results. Clin Can Res 8:2177-2187, 2002.

Kantarjian H, Cortes J, O’Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Jeha S, Rios MB, Letvak L, Bochinski K, Arlinghaus R, Talpaz M. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood 101:97-100, 2003.

Kantarjian H, Talpaz M, O’Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Shan J, Rios MB, Cortes J. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood 101:473-475, 2003.

Kantarjian H, Talpaz M, O’Brien S, Garcia-Manero G, Verstovsek S, Giles F, Rios MB, Shan J, Letvak L, Thomas D, Faderl S, Ferrajoli A, Cortes J. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood 103:2873-8, 2004.

Demonstrated the effectiveness of two new drugs, dasatinib and nilotinib, in Gleevec-resistant chronic myelocytic leukemia, leading to FDA approval.

Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542-2551.

Demonstrated that decitabine acts in leukemia and myelodysplastic syndrome by preventing cancer cells from turning off the expression of critical suppressor genes, leading to FDA approval.

Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM. Phase I study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2’-deoxycytidine (decitabine) in hematopoietic malignancies. Blood. 2004;103(5):1635-1640.

Yang AS, Doshi KD, Choi SW, Mason JB, Mannari RK, Gharybian V, Luna R, Rashid A, Shen L, Estecio MR, Kantarjian HM, Garcia-Manero G, Issa JP. DNA methylation changes after 5-aza-2’-deoxycytidine therapy in patients with leukemia. Cancer Res. 2006;66(10):5495-5503.

Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O’Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davis J, Giles F, Saba HI, Issa JP Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007;109(1):52-57.

Performed pivotal trial of lenalidomide plus dexamethasone for relapsed multiple myeloma patients, leading to FDA approval of lenalidomide.

Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD, for the Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. New Engl J Med. 2007;357(21):2133-2142.

Completed the BATTLE clinical trial of four drugs, each targeting a different signaling pathway, which created a new paradigm supporting the use of biomarkers to predict sensitivity or resistance of patients to therapy, transforming personalized therapy for lung cancer.

Kim ES,* Herbst RS,* Wistuba II,* Lee JJ,* Blumenschein GR, Tsao A, Stewart DJ, Hicks ME, Erasmus J, Gupta S, Alden CM, Liu S, Tang X, Khuri FR, Tran HT, Johnson BE, Heymach JV, Mao L, Fossella F, Kies M, Papadimitrakopoulou V, Davis SE, Lippman SM,† Hong WK† (*Co-lead authors; †Co-senior authors). The BATTLE trial: personalizing therapy for lung cancer. Cancer Discovery 2011.[In press]