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Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study
Author(s) -
Jakubowiak Andrzej J.,
Richardson Paul G.,
Zimmerman Todd,
Alsina Melissa,
Kaufman Jonathan L.,
Kandarpa Malathi,
Kraftson Stephanie,
Ross Charles W.,
Harvey Colleen,
Hideshima Teru,
Sportelli Peter,
Poradosu Enrique,
Gardner Lesa,
Giusti Kathy,
Anderson Kenneth C.
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09173.x
Subject(s) - lenalidomide , medicine , dexamethasone , neutropenia , tolerability , multiple myeloma , adverse effect , refractory (planetary science) , phases of clinical research , gastroenterology , febrile neutropenia , oncology , surgery , clinical trial , chemotherapy , physics , astrobiology
Summary The combination of lenalidomide–dexamethasone is active in multiple myeloma ( MM ). Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells to lenalidomide and dexamethasone, providing the rationale for this Phase I, multicentre, single‐arm study to assess the safety and determine the maximum‐tolerated dose ( MTD ) of perifosine–lenalidomide–dexamethasone in relapsed and relapsed/refractory MM . Patients received escalating doses of perifosine 50–100 mg daily and lenalidomide 15–25 mg once daily on days 1–21 of each 28‐d cycle, plus dexamethasone 20–40 mg weekly thereafter, as indicated. Thirty‐two patients were enrolled across four dose cohorts. MTD was not reached, with 31 patients evaluable for safety/tolerability. The most common all‐causality grade 1‐2 adverse events were fatigue (48%) and diarrhoea (45%), and grade 3–4 neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). Among 30 evaluable patients, 73% (95% confidence interval, 57·5–89·2%) achieved a minimal response or better, including 50% with a partial response or better. Median progression‐free survival was 10·8 months and median overall survival 30·6 months. Response was associated with phospho‐Akt in pharmacodynamic studies. Perifosine–lenalidomide–dexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory MM .