TY - JOUR
T1 - A phase I/II trial of carfilzomib, pegylated liposomal doxorubicin, and dexamethasone for the treatment of relapsed/refractory multiple myeloma
AU - Schroeder, Mark A.
AU - Fiala, Mark A.
AU - Huselton, Eric
AU - Cardone, Michael H.
AU - Jaeger, Savina
AU - Jean, Sae Rin
AU - Shea, Kathryn
AU - Ghobadi, Armin
AU - Wildes, Tanya
AU - Stockerl-Goldstein, Keith E.
AU - Vij, Ravi
N1 - Funding Information:
the use of the Clinical Trials Core that provided protocol development services. We would also like to thank the members of Washington University School of Medicine Division of Oncology Clinical Trials office who provided study coordination and data management. The Siteman Cancer Center is supported, in part, by an NCI Cancer Center Support Grant #P30 CA91842. BH3 profiling was supported by NCI-SBIR R44CA203610 awarded to Eutropics. Amgen Inc. provided funding and materials for this study.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Purpose: Pegylated liposomal doxorubicin (PLD) combined with bortezomib is an effective salvage regimen for relapsed refractory multiple myeloma (RRMM). Carfilzomib, a second-generation proteasome inhibitor, has clinical efficacy even among bortezomib-refractory patients. Patients and Methods: We performed a phase I/II trial of carfilzomib, PLD, and dexamethasone (KDD) with the primary endpoints being safety and efficacy (NCT01246063). Twentythree patients were enrolled in the phase I portion and theMTD of carfilzomib was determined to be 56 mg/m2 (days 1, 2, 8, 9, 15, and16)when combinedwithPLD(30mg/m2onday 8)and dexamethasone (20mg ondays 1, 2, 8, 9,15, and16). Seventeen additional patients were enrolled in the phase II portion. Results: KDD was determined to be well tolerated with the only common grade 3/4 nonhematologic adverse events of infection. Grade 3/4 hematologic toxicity included lymphopenia (63%), thrombocytopenia (40%), anemia (40%), and neutropenia (28%). In the cohort of patients treated at the MTD, where median prior therapies were 2% and 42% were refractory to bortezomib, the overall response rate was 83% (20/24) with 54% (13/24) having a very good partial response or better. The median progression-free survival was 13.7 months (95% CI, 5.0-21.7). Conclusions: This trial is the first to report outcomes using a triplet regimen of high-dose carfilzomib. KDD was well tolerated and appears efficacious in RRMM. Additional study is needed to more precisely determine patient outcomes with this regimen and its utility compared with other carfilzomib containing salvage regimens.
AB - Purpose: Pegylated liposomal doxorubicin (PLD) combined with bortezomib is an effective salvage regimen for relapsed refractory multiple myeloma (RRMM). Carfilzomib, a second-generation proteasome inhibitor, has clinical efficacy even among bortezomib-refractory patients. Patients and Methods: We performed a phase I/II trial of carfilzomib, PLD, and dexamethasone (KDD) with the primary endpoints being safety and efficacy (NCT01246063). Twentythree patients were enrolled in the phase I portion and theMTD of carfilzomib was determined to be 56 mg/m2 (days 1, 2, 8, 9, 15, and16)when combinedwithPLD(30mg/m2onday 8)and dexamethasone (20mg ondays 1, 2, 8, 9,15, and16). Seventeen additional patients were enrolled in the phase II portion. Results: KDD was determined to be well tolerated with the only common grade 3/4 nonhematologic adverse events of infection. Grade 3/4 hematologic toxicity included lymphopenia (63%), thrombocytopenia (40%), anemia (40%), and neutropenia (28%). In the cohort of patients treated at the MTD, where median prior therapies were 2% and 42% were refractory to bortezomib, the overall response rate was 83% (20/24) with 54% (13/24) having a very good partial response or better. The median progression-free survival was 13.7 months (95% CI, 5.0-21.7). Conclusions: This trial is the first to report outcomes using a triplet regimen of high-dose carfilzomib. KDD was well tolerated and appears efficacious in RRMM. Additional study is needed to more precisely determine patient outcomes with this regimen and its utility compared with other carfilzomib containing salvage regimens.
UR - http://www.scopus.com/inward/record.url?scp=85069264626&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-1909
DO - 10.1158/1078-0432.CCR-18-1909
M3 - Article
C2 - 30952640
AN - SCOPUS:85069264626
VL - 25
SP - 3776
EP - 3783
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -