Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial

• Published in: Blood Vol. 118; no. 3; pp. 535 - 543
• Main Authors: Jakubowiak, Andrzej J., Griffith, Kent A., Reece, Donna E., Hofmeister, Craig C., Lonial, Sagar, Zimmerman, Todd M., Campagnaro, Erica L., Schlossman, Robert L., Laubach, Jacob P., Raje, Noopur S., Anderson, Tara, Mietzel, Melissa A., Harvey, Colleen K., Wear, Sandra M., Barrickman, Jennifer C., Tendler, Craig L., Esseltine, Dixie-Lee, Kelley, Susan L., Kaminski, Mark S., Anderson, Kenneth C., Richardson, Paul G.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 21.07.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Adult; Aged; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Boronic Acids - administration & dosage; Boronic Acids - adverse effects; Bortezomib; Clinical Trials and Observations; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Female; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Lenalidomide; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoid Neoplasia; Male; Medical sciences; Middle Aged; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Prospective Studies; Pyrazines - administration & dosage; Pyrazines - adverse effects; Survival Rate; Thalidomide - administration & dosage; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Antineoplastic agent; Early stage; Research; Myeloma; Doxorubicin; Isomerases; Immunoglobulinopathy; Lymphoproliferative syndrome; Clinical trial; Pegylated form; Corticosteroid; DNA topoisomerase (ATP-hydrolysing); Immunopathology; Bortezomib; Dexamethasone; Hematology; Lenalidomide; Enzyme; Steroid hormone; Enzyme inhibitor; Liposome; Malignant hemopathy; Topoisomerase II inhibitor; Analog; Proteasome inhibitor; Dipeptides; Anthracyclins; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-02-334755

This phase 1/2 trial evaluated combination lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (RVDD) in newly diagnosed multiple myeloma (MM) patients. Patients received RVDD at 4 dose levels, including the maximum tolerated dose (MTD). Patients with a very good partial response or better (≥ VGPR) after cycle 4 proceeded to autologous stem cell transplantation or continued treatment. The primary objectives were MTD evaluation and response to RVDD after 4 and 8 cycles. Seventy-two patients received a median of 4.5 cycles. The MTDs were lenalidomide 25 mg, bortezomib 1.3 mg/m2, pegylated liposomal doxorubicin 30 mg/m2, and dexamethasone 20/10 mg, as established with 3-week cycles. The most common adverse events were fatigue, constipation, sensory neuropathy, and infection; there was no treatment-related mortality. Response rates after 4 and 8 cycles were 96% and 95% partial response or better, 57% and 65% ≥ VGPR, and 29% and 35% complete or near-complete response, respectively. After a median follow-up of 15.5 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The estimated 18-month PFS and OS were 80.8% and 98.6%, respectively. RVDD was generally well tolerated and highly active, warranting further study in newly diagnosed MM patients. This trial was registered at www.clinicaltrials.gov as NCT00724568.