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Long‐term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom Macroglobulinemia
Author(s) -
Ghobrial Irene M.,
Witzig Thomas E.,
Gertz Morie,
LaPlant Betsy,
Hayman Suzanne,
Camoriano John,
Lacy Martha,
Bergsagel P. Leif,
Chuma Stacey,
DeAngelo Daniel,
Treon Steven P.
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23620
Subject(s) - everolimus , medicine , gastroenterology , macroglobulinemia , leukopenia , waldenstrom macroglobulinemia , refractory (planetary science) , progression free survival , anemia , surgery , chemotherapy , oncology , lymphoma , physics , astrobiology , multiple myeloma
Everolimus is an oral raptor mTOR inhibitor and has shown activity in patients with Waldenstrom's macroglobulinemia (WM). This study examines a large cohort of patients with relapsed/refractory WM with long‐term follow up for survival. Patients were eligible if they had measurable disease, a platelet count > 75,000 × 10 6 /L, an absolute neutrophil count > 1,000 × 10 6 /L. Patients received everolimus 10 mg PO daily and were evaluated monthly. A success was defined as a complete or partial response (PR); minor responses (MR) were recorded and considered to be of clinical benefit. Sixty patients were enrolled and treated. The overall response rate (ORR) was 50% (all PR); the clinical benefit rate including MR or better was 73% (95% CI: 60–84%) with 23% MR. The median time to response for patients who achieved PR was 2 months (range, 1–26). The median duration of response has not been reached and median progression‐free survival (PFS) was 21 months. Grade 3 or higher toxicities (at least possibly related to everolimus) were observed in 67% of patients. The most common grade 3 or 4 toxicities were anemia (27%), leukopenia (22%), and thrombocytopenia (20%). Other nonhematological toxicities were diarrhea (5%), fatigue (8%), stomatitis (8%) and pulmonary toxicity (5%). Everolimus has a high single‐agent activity of 73% including MR, with a progression free survival of 21 months, indicating that this agent is active in relapsed/refractory WM. Am. J. Hematol. 89:237–242, 2014. © 2013 Wiley Periodicals, Inc