Real-world clinical outcomes in patients with relapsed and refractory multiple myeloma receiving VTD-PACE treatment in the era of monoclonal antibodies.

Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1 months, during which they received a median of two cycles of VTD-PACE. The overall response rate (ORR) was 66.7%; ORRs of 53.1 and 82.1% were noted in patients with ≥ 4 and ≤ 3 prior lines (P = 0.027), respectively. The median overall survival (OS) was 17 months, with a median progression-free survival (PFS) of 9.8 months. Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and OS of patients who received or did not receive HSCT or CART after VTD-PACE treatment. Patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE showed a trend of longer PFS and OS than those who did not undergo subsequent HSCT or CART. The median OS in patients with and without renal dysfunction was 10.7 months and 21.5 months, respectively (P = 0.0091). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response can be expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use.

Sequential autologous and allogeneic stem cell transplantation for treatment of primary plasma cell leukemia: A case report.

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell disorder, which accounts for ~70% of all PCL. Survival of pPCL remains poor, and is related with early mortality. There is no standard therapy for patients with pPCL. In the present study, a 26-year-old man who was diagnosed with pPCL was reported. The patient achieved stringent complete remission to the successful treatment of intensive chemotherapy combined with sequential autologous and allogeneic stem cell transplantation (SCT) followed by maintenance therapy with oral administration of ixazomib, thalidomide and dexamethasone (IRD regimen). Development of complex treatment algorithms that combine novel agents, SCT and post-transplantation remission strategies may translate into survival in patients with pPCL.

VTd-PACE and VTd-PACE-like regimens are effective salvage therapies in difficult-to-treat relapsed/refractory multiple myeloma: a single-center experience.

Although treatment options for multiple myeloma (MM) are rapidly evolving, there still remain difficult-to-treat situations, especially in relapsed and/or refractory (r/r) disease. When modern therapies are exhausted, or emergency treatment is needed for high tumor burden, classic chemotherapy combination regimens like the VTd-PACE regimen and its modifications (PACE-M) may also be beneficial as bridging to subsequent treatment options. This single-center retrospective analysis aimed to investigate the outcome of VTd-PACE and PACE-M salvage therapy in 31 heavily pretreated r/r MM patients. The primary objective was the overall response rate (ORR). Secondary objectives were median progression-free survival (mPFS), median overall survival (mOS), safety, and renal response. Median age was 59 years (range 39-75), and 71% of patients were male. R-ISS stratification showed high-risk MM in 48%. The median number of prior therapies was 3, with 23 patients being triple- and 12 penta-refractory (74% and 39%). ORR was 71%, including 23% of patients achieving a very good partial response. Median duration of follow-up was 15 months (range 0-29 months). mPFS and mOS were 3 months (95% CI 0.27-5.74) and 11 months (95% CI 3.66-18.35), respectively. In 26 patients (83.9%), at least one subsequent treatment (stem cell transplant or BCMA-directed) was administered. Renal function significantly improved after VTd-PACE or PACE-M treatment (p = 0.032). Non-hematological adverse events ≥ grade 3 were predominantly infections. VTd-PACE and PACE-M are effective salvage therapies in difficult-to-treat situations in heavily pre-treated r/r MM, including patients with impaired renal function. VTd-PACE and PACE-M can be successfully used as bridging therapy for subsequent treatment.

Bortezomib-thalidomide-dexamethasone-cisplatin-doxorubicin-cyclophosphamide-etoposide as a Salvage and Bridging Regimen before Hematopoietic Stem Cell Transplantation for Relapsed or Refractory Multiple Myeloma.

Objective Currently, treatment of relapsed or refractory multiple myeloma is challenging. Although bortezomib-thalidomide-dexamethasone-cisplatin-doxorubicin-cyclophosphamide-etoposide (VTD-PACE), a potent combination of a proteasome inhibitor, immunomodulatory drug, and conventional chemotherapeutics, is a widely used regimen, its efficacy and safety are unclear. Methods We retrospectively analyzed the clinical data of 35 patients treated with VTD-PACE. Results The overall response rate was 65.7% (complete response, 5.7%). The median progression-free survival (PFS) and overall survival (OS) were 8.0 [95% confidence interval (CI), 0.9-15.0] and 20.0 (95% CI, 17.5-22.5) months, respectively. Twenty-two (62.9%) patients developed grade 3-4 infections, and no therapy-related deaths occurred. Sixteen of 25 patients (64%) underwent stem cell harvest successfully with more than 2.0×106/kg of CD34 cells after VTD-PACE. Twenty-two patients underwent autologous or allogeneic stem cell transplantation (SCT). The response and survival durations were short in patients without SCT after VTD-PACE [median PFS: 4.0 (95% CI, 2.7-5.3) months; OS: 14.0 (6.9-21.0) months]; however, these responses significantly improved with SCT following VTD-PACE. The PFS was 8.0 (NA) months (p=0.024), and the OS was 21.0 (19.1-22.8) months (p=0.019). Conclusion VTD-PACE is an effective and tolerable salvage regimen and feasible bridging therapy for SCT.

A comparison of salvage infusional chemotherapy regimens for recurrent/refractory multiple myeloma.

BACKGROUND: Despite the impact of proteasome inhibitors and immunomodulatory agents, infusional chemotherapy regimens continue to be used for patients with multiple myeloma. To the authors' knowledge, contemporary data regarding salvage chemotherapy regimens are sparse, with no direct comparisons. METHODS: The authors performed a single-institution study comparing 3 salvage chemotherapy regimens in 107 patients with recurrent/refractory multiple myeloma: dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in 52 patients; bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VTD-PACE) in 22 patients; and cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) in 33 patients. RESULTS: Differences between treatment groups existed, including higher baseline creatinine for patients treated with CVAD (P<.001) and greater prior use of infusional chemotherapy for those receiving VTD-PACE (P<.001). There was no significant difference in response noted among the 3 regimens: 55% overall (P = .18). For the intent-to-transplant population, a similar percentage were successfully bridged to transplant without further therapy (62%; P = .9). There was no difference in survival observed across the 3 regimens, with an overall median progression-free survival of 4.5 months (95% confidence interval, 3.6-5.5 months [P = .8]) and a median overall survival of 8.5 months (95% confidence interval, 6.1-11 months [P = .8]). Furthermore, there was no statistically significant difference noted among clinically relevant adverse events, although there was a suggestion of fewer adverse events with DCEP. Patients treated with the intent to transplant had superior outcomes for response (odds ratio, 3.40; P = .01), progression-free survival (hazard ratio, 0.28; P<.001), and overall survival (hazard ratio, 0.19; P<.001). CONCLUSIONS: The 3 salvage regimens demonstrated similar responses, survival, and adverse events. Given the short response durations observed in the recurrent/refractory disease setting, infusional chemotherapy is best suited for cytoreduction before more definitive therapy is administered.