Phase II study of pegylated liposomal doxorubicin, low‐dose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma

Abstract

Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ≥VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m2 intravenously, day 1; dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with high-dose melphalan or with maintenance lenalidomide and dexamethasone. In 57 patients, we found that the overall response rate and rate of very good partial response and better on intent-to-treat, our primary endpoints, were 77.2% and 42.1%, respectively, with responses per the International Myeloma Working Group. Median progression-free survival was 28 months (95% CI 18.1-34.8), with 1- and 2-year overall survival rates of 98.1 and 79.6%. During induction, grade 3/4 toxicities were neutropenia (49.1%), anemia (15.8%), thrombocytopenia (7%), fatigue (14%), febrile neutropenia (8.8%), and venous thromboembolic events (8.8%). During maintenance, grade 3/4 toxicities were mainly hematologic. We found this combination to be active in patients with newly diagnosed myeloma, with results comparable to other lenalidomide-based induction strategies without proteasome inhibition. In addition, maintenance therapy with lenalidomide was well tolerated.

Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

“…This forest plot illustrates the percentage of events per 100 patient‐cycles for respective therapies. BPR indicates bendamustine, prednisone, and lenalidomide; CPR, cyclophosphamide, prednisone, and lenalidomide; HDACi, histone deacetylase inhibitor; MoAB, monoclonal antibody; MPR, melphalan, prednisone, and lenalidomide; mTORi, mammalian target of rapamycin inhibitor; PI, proteasome inhibitor; R, lenalidomide; Rd, lenalidomide and low‐dose dexamethasone …”

“…In total, 245 duplicate records were removed, and 1127 records were screened. Ultimately, 51 clinical trials with 61 Len‐containing treatment arms and 9069 patients were included for the analysis based on a priori selection criteria (Fig. ) …”

Anti-VEGF Drugs in the Treatment of Multiple Myeloma Patients

“…Multiple different agents including cyclophosphamide [ 210 , 211 , 212 ], bendamustine [ 213 , 214 ], melphalan [ 215 ], liposomal doxorubicin [ 216 , 217 ], proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) [ 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 ], histone deacetylases (HDAC) inhibitors (panobinostat and ricolinostat) [ 226 , 227 ], and monoclonal antibodies (elotuzumab, daratumumab, and pembrolizumab) [ 228 , 229 , 230 , 231 , 232 ] have been combined with lenalidomide with convincing results. Other trials evaluating the association of lenalidomide with new molecules are ongoing.…”

Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience

“…As with thalidomide, lenalidomide has been studied in combination with multiple different agents including alkylating agents (low-dose cyclophosphamide [49–51], bendamustine [52, 53], melphalan [54]), liposomal doxorubicin [55, 56], proteasome inhibitors (bortezomib [57, 58], carfilzomib [59–61], ixazomib [62]), HDAC inhibitors (panobinostat [63], ricolinostat [64]), and monoclonal antibodies (elotuzumab [65], daratumumab [66], pembrolizumab [67]). Several recent phase III studies have been reported in which lenalidomide/dexamethasone was compared with triplet regimens in the relapsed/refractory setting [68–71].…”