Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study
Open Access
- 3 July 2014
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 124 (1), 63-69
- https://doi.org/10.1182/blood-2014-03-563759
Abstract
This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787. Key Points This is the first study of carfilzomib-cyclophosphamide-dexamethasone in elderly patients with newly diagnosed multiple myeloma. Carfilzomib-cyclophosphamide-dexamethasone induced high complete response rates and was associated with low toxicity.Keywords
This publication has 28 references indexed in Scilit:
- Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trialsPublished by Ferrata Storti Foundation (Haematologica) ,2013
- Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trialsHaematologica, 2012
- IMWG consensus on maintenance therapy in multiple myelomaBlood, 2012
- Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantationBlood, 2011
- Multiple MyelomaNew England Journal of Medicine, 2011
- Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendationsHaematologica, 2010
- Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trialThe Lancet Oncology, 2009
- DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myelomaAnnals of Hematology, 2009
- Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple MyelomaNew England Journal of Medicine, 2008
- Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trialThe Lancet, 2006