title: Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma.
abstract: We conducted a phase II study of the AKT inhibitor, MK2206 in patients with relapsed or refractory lymphoma of any histology excluding Burkitt lymphoma or lymphoblastic lymphoma. MK-2206 was administered orally at 200 mg once weekly in 28-d cycles up to 12 cycles in the absence of progression or significant toxicity. The dose was adjusted based on tolerance. A total of 59 patients were enrolled. The final doses patients received were 300 mg (n = 33), 250 mg (n = 2), 200 mg (n = 16) and 135 mg (n = 8). Based on intent-to-treat analysis, objective response was observed in 8 (14%) patients (2 complete response and 6 partial response), with median response duration of 5·8 months. The overall response rate was 20% in 25 patients with classical Hodgkin lymphoma. Rash was the most common toxicity (any grade 53%, Grade 3 in 15%) and was observed in a dose-dependent manner. The correlative cytokine analysis showed paradoxical increase in several cytokines, which may be explained by negative feedback mechanism induced by the on-target effect of AKT inhibitor. Our data demonstrate that MK2206 has a favourable safety profile with a modest activity in patients with relapsed Hodgkin lymphoma. The future studies should explore mechanism-based combinations (clinicaltrials.gov NCT01258998).
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fanale
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Romaguera
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Fowler
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Copeland
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sattva
authors.initials: S
authors.lastname: Neelapu
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology; D025461:Feedback, Physiological; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects / Q000627:therapeutic use*; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D012008:Recurrence; D016879:Salvage Therapy; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; clinical trials; lymphoma; target therapy