ASH Clinical News July 2016 | Page 30

Written in Blood STRATUS MM-010 Trial: Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma There is an unmet need for relapsed/ refractory multiple myeloma (MM) patients who have failed treatment with newer agents (e.g., lenalidomide and bortezomib), as overall survival (OS) is decreased in this population. In the pivotal phase II MM-002 and phase III MM-003 clinical trials, the combination of pomalidomide and lowdose dexamethasone was shown to improve response and survival rates compared with pomalidomide alone and with high-dose dexamethasone, respectively, among patients with relapsed/refractory MM. To further assess the safety and efficacy of pomalidomide plus low-dose dexamethasone, Meletios A. Dimopoulos, MD, from the National and Kapodistrian University of Athens School of Medicine in Greece, and investigators conducted the open-label, single-arm, phase IIIb STRATUS MM-010 trial. According to results published in Blood, Dr. Dimopoulos and coauthors confirmed the benefit of pomalidomide plus low-dose dexamethasone, with an overall response rate (ORR; the study’s primary endpoint) of 32.6 percent (95% CI 29-36.2) and a median duration of response (DOR; one of the study’s secondary endpoints) of 7.4 months (95% CI 4.2-5.6). MM-010 STRATUS included 682 patients with relapsed/refractory MM enrolled at 91 centers in 19 European countries between November 2012 and December 2014. Adult patients were considered for inclusion if they: • had received ≥2 previous lines of treatment, including ≥2 cycles of lenalidomide and bortezomib (alone or in combination) and adequate prior alkylator therapy (≥4 cycles or progressive disease [PD] after ≥2 cycles or received alkylator treatment as a part of a stem cell transplant) • had failed treatment with both bortezomib and lenalidomide (defined as PD on or within 60 days of treatment, PD ≤6 months after achieving a partial response, or intolerance to bortezomib) Patients were excluded if they had received a hematopoietic cell transplant or if they were planning for or eligible for transplant. The median patient age was 28 ASH Clinical News 66 years, and median time since initial diagnosis was 5.3 years. Patients had been treated with a median of five prior antimyeloma treatment regimens (range = 2-18 treatments). Patients received pomalidomide 4 mg on days one through 21 of a 28-day cycle and low-dose dexamethasone 40 mg (if ≤75 years) or 20 mg (if >75 years) on days one, eight, 15, and 22 of a 28-day cycle. Patients who discontinued treatment were followed every three months for up to five years after enrollment to monitor subsequent treatments, dates of progression, survival, and second primary malignancies (SPMs). S:6.75” The study’s primary safety endpoint was the incidence of adverse events (AEs; type, frequency, severity, and relationship to drug), including SPMs. Secondary endpoints included pomalidomide exposure, ORR, DOR, progression-free survival (PFS), overall OS, time to response, and time to progression. After a median follow-up of 16.8 months, 15.2 percent of patients (n=104) remained on treatment and 83.9 percent BOSULIF is indicated for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. In the treatment of adult patients with Ph+ CML with resistance or intolerance to prior therapy Everyone has a distinct profile Consider your patient.Consider BOSULIF. ( b o s u t inib) Bosutinib (BOSULIF®) is recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a treatment option for patients with CML in need of 2nd- or later-line TKI therapy.1 Study design: BOSULIF 500 mg once-daily treatment was studied in a single-arm, Phase 1/2, open-label, multicenter trial (N=546) in patients with CP, AP, or BP CML in second line (after imatinib) or in third line (after imatinib followed by dasatinib and/or nilotinib). Of the 546 patients enrolled, 73% were imatinib resistant and 27% were imatinib intolerant.2 AP=accelerated phase; BP=blast phase; CP=chronic phase. IMPORTANT SAFETY INFORMATION Contraindication: History of hypersensitivity to BOSULIF. Reactions have included anaphylaxis. Anaphylactic shock occurred in less than 0.2% of treated patients in clinical trials. Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and abdominal pain can occur. In the clinical trial, median time to onset for diarrhea was 2 days, median duration was 1 day, and median number of episodes per patient was 3 (range 1-221). Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary. Myelosuppression: Thrombocytopenia, anemia, and neutropenia can occur. Perform complete blood counts weekly for the first month and then monthly or as clinically indicated. Withhold, dose reduce, or discontinue BOSULIF as necessary. Hepatic Toxicity: Twenty percent of patients experienced an increase in either ALT or AST. Liver en zyme elevation usually occurs early in treatment. Perform hepatic enzyme tests monthly for the first 3 months and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Drug-induced liver injury has occurred. Withhold, dose reduce, or discontinue BOSULIF as necessary. In patients with mild, moderate, or severe hepatic impairment, the recommended starting dose is 200 mg daily. Renal Toxicity: An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF. Monitor renal function at baseline and during therapy, with particular attention to patients with preexisting renal impairment or risk factors. Consider dose adjustment in patients with baseline and treatment emergent renal impairment. The recommended starting doses for patients with severe renal impairment (CrCL <30 mL/min) or moderate renal impairment (CrCL 30-50 mL/min) are 300 mg and 400 mg daily, respectively. Fluid Retention: Fluid retention can occur and may cause pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary. B:15.5” T:15.25” G:.5”