Efficacy of VDT PACE‐like regimens in treatment of relapsed/refractory multiple myeloma

Abstract

Experience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE-like regimens: VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent-to-treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range 0.02-11.4) separated diagnosis of myeloma and inititation of VPLR. High-risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range 1-14) prior therapies, including stem cell transplant (SCT) in 66.7% patients. Ninety-five (67.4%) patients received VDT PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other VPLRs. Patients received a median of 1 cycle (range 1-9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very good PR in 10.3% patients. Median progression-free survival was 3.1 months (95% CI, 1.9-3.9) and median overall survival (OS) was 8.1 months (CI, 6.2-9.9). One-hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3-20.8). Age ≥ 60 years (hazard ratio [HR] 2.3 [CI, 1.4-3.7]; P = 0.0008) and R-ISS III stage (HR- 2.4 [CI, 1.3-4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR. VPLRs are effective in heavily pre-treated RRMM. In fit patients, SCT can be used to consolidate the response to VPLR.

Use of KRD-PACE as Salvage Therapy in Aggressive, Relapsed/Bortezomib-Refractory Extramedullary Multiple Myeloma: A Report of Two Cases and Literature Review

“…ere was a trend toward more febrile neutropenia with VTD-PACE and prolonged hospitalization among patients treated with CVAD, but there were no statistically significant differences in adverse events among the 3 regimens [15]. In a retrospective study of 141 patients with RRMM treated with VTD-PACElike regimens, ORR was 54%, OS was 8.1 months, and PFS was 3.1 months [16]. Most patients received 1-2 cycles of a VTD-PACE-like regimen, 85% were refractory to V, and 60% were refractory to R. Patients required a median of 4 packed red cell transfusions and 4 platelet transfusions during cycle 1 [16].…”

“…In a retrospective study of 141 patients with RRMM treated with VTD-PACElike regimens, ORR was 54%, OS was 8.1 months, and PFS was 3.1 months [16]. Most patients received 1-2 cycles of a VTD-PACE-like regimen, 85% were refractory to V, and 60% were refractory to R. Patients required a median of 4 packed red cell transfusions and 4 platelet transfusions during cycle 1 [16]. Median time to recovery of absolute neutrophil count and platelet count from initiation of a VTD-PACE-like regimen was 18 (range, 12-44) and 21(range 11-45) days, respectively [16].…”

NCCN Guidelines Insights: Multiple Myeloma, Version 3.2018

“…Patients with an aggressive relapse may need multidrug combinations for effective disease control; VTD-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) [38][39][40] is one such regimen that is now an option listed under "Useful in Certain Circumstances" for treating previously treated aggressive MM (MYEL-D, 3 of 3; page 15).…”

Aggressive Central Nervous System Relapse after Autologous Stem Cell Transplant in Multiple Myeloma: Case Reports and Literature Review

“…Standard chemotherapy used on MM as alkylating agents penetrates the BBB very poorly, with only 10% of melphalan levels found at LCR of treated patients [7]. e intensive chemotherapy combinations such as PACE are useful as salvage regimens in refractory/relapsed MM and PCL and appear to be a robust approach to systemic treatment to prevent further hematogenous spread to CNS and elimination of residual clones [46]. As a sole treatment for CNS disease, it is insufficient.…”