ASH Clinical News November 2015 | Page 39

CLINICAL NEWS Patients were excluded from the study if they had congestive heart failure, symptomatic ischemia, conduction system abnormalities uncontrolled by conventional intervention, myocardial infarction in the previous six months or uncontrolled hypertension, or significant neuropathy. The study’s primary endpoint was identifying the MTD. Secondary endpoints included the preliminary efficacy of CPD in terms of overall response rate (ORR), complete response rate, very good partial response (VGPR) rate, partial response rate (PRR), minimal response rate (MRR), time to progression, progression-free survival (PFS), and overall survival (OS). Per treatment protocol, all patients received: • Carfilzomib intravenously over 30 minutes on days 1, 2, 8, 9, 15, and 16 every 28 days for the first six cycles, with a starting dose of 20/27 mg/m2 • Pomalidomide orally once daily on days 1 through 21 every 28 days, with a 4 mg initial starting dose • Dexamethasone 40 mg delivered orally or intravenously on a weekly basis on days 1, 8, 15, and 22 of 28day cycles After the first four cycles, it was recommended that the dexamethasone dose be reduced to 20 mg. After six cycles of treatment, patients could continue on maintenance therapy as long as, in the eyes of the investigator, they were deriving clinical benefit from the drugs. All patients were evaluated for hematologic and non-hematologic dose-limiting toxicities. Of the 32 patients included in the study, 28 patients had an adverse event related to the study treatment or an infection: 63 percent of patients (n=20) had a grade 3 event, 31 percent (n=10) had a grade 4 event, and 6 percent of patients (n=2) had fatal events of pneumonia and pulmonary embolism (TABLE 1). Five patients (16%) received platelets transfusions, and 19 patients (59%) required at least one transfusion of red blood cells (median = 1; range 0-13). “Treatment-emergent peripheral neuropathy was uncommon, with six patients experiencing grade 1 peripheral neuropathy and one patient experiencing grade 2 peripheral neuropathy,” the authors noted. Additional reported hematologic and non-hematologic toxicities can be found in TABLE 1. Eight patients had dose reductions during therapy, and seven patients discontinued treatment due to adverse events. Patients received a median of seven treatment cycles. In terms of the secondary endpoints, the ORR was 50 percent among the study patients, with: • 16% of patients achieving VGPR • 34% achieving PRR • 16% achieving MRR • 25% with stable disease An analysis of response rate according to MM subtype is provided in TABLE 2. After a median follow-up of 26.3 months (range = 1-37 months), the median TABLE 1. Adverse Events, by Maximum Grade Reported PFS was 7.2 months Grade (95% CI 3-9) and Total (N=32) median OS was 20.6 1 2 3 4 5 months (95% CI 11.9Hematologic adverse events, n 28.7), with a 12-month Anemia 0 4 5 1 0 10 OS rate of 67 percent. Thrombocytopenia 0 3 4 3 0 10 “[CPD] is quickly becoming a standardNeutropenia 0 4 10 4 0 18 of-care option for Febrile neutropenia 0 0 2 0 0 2 patients with lenalidNon-hematologic adverse events, n omide-refractory myDiarrhea 4 1 0 0 0 5 eloma, with response Constipation 6 0 0 0 0 6 rates and survival superior to either drug Nausea 1 1 1 0 0 3 alone,” Dr. Shah said, Emesis 0 1 1 0 0 2 however there were Fatigue 5 9 1 0 0 15 limitations with this Dyspnea 8 2 1 0 0 11 study. For instance, grade 3 rashes ocRash 4 0 1 0 0 5 curred, which limited Neuropathy/paresthesia 6 1 0 0 0 7 the researchers’ ability Congestive heart failure 0 0 1 0 0 1 to escalate the dose, Muscle spasms 4 2 0 0 0 6 and, as a result, the MTD may have been Transient ischemic attack 0 0 1 0 0 1 underestimated. AddiPulmonary emboli 0 0 1 0 1 2 tionally, the number of Deep vein thrombosis 0 1 0 0 0 1 patients included in the Creatinine elevation 5 4 1 2 0 12 study was limited. The Pneumonia 0 0 3 0 1 4 researchers suggested that in future studies, a subsequent dose escaTABLE 2. Response Rate in All Intent-to-Treat Patients and by Cytogenetic lation is conducted in less heavily pretreated Abnormalities patients to reevaluate All evaluable Hyperdiploid Response Rate Del(13) (n=9) Del(17p) (n=5) the MTD of this treatpatients (n=32) (n=10) ment combination. ● Overall response rate 16 (50%) 5 (50%) 1 (11%) 4 (80%) Very good partial response 6 (16%) 1 (10%) 1 (11%) 1 (20%) Partial response 11 (34%) 4 (40%) 0 3 (60%) Minimal response 5 (16%) 3 (30%) 3 (33%) 0 Stable disease 8 (25%) 2 (20%) 5 (56%) 1 (20%) Progressive disease 3 (9%) 0 0 0 ASHClinicalNews.org REFERENCE Shah JJ, Stadtmauer EA, Abonour R, et al. Carfilzomib, pomalidomide, and dexamethasone (CPD) in patients with relapsed and/or refractory multiple myeloma. Blood. 2015 September 4. [Epub ahead of print] ASH Clinical News 37