A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma.
Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27-68). Patients had received a median of six prior therapies (range, 3-14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24-71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant.
Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, Minnesota 55905, USA.
Patrick B
PB
Johnston
David J
DJ
Inwards
Joseph P
JP
Colgan
Betsy R
BR
Laplant
Brian F
BF
Kabat
Thomas M
TM
Habermann
Ivana N
IN
Micallef
Luis F
LF
Porrata
Stephen M
SM
Ansell
Craig B
CB
Reeder
Vivek
V
Roy
Thomas E
TE
Witzig
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D017277:Drug Approval; D000068338:Everolimus; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011506:Proteins; D016879:Salvage Therapy; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000502:physiology
D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000068338:Everolimus; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus