scholarly journals Real-Life Experience With First-Line Therapy Bortezomib Plus Melphalan and Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma Ineligible for High Dose Chemotherapy With Autologous Stem-Cell Transplantation

2021 ◽  
Vol 8 ◽  
Author(s):  
Gabriele Buda ◽  
Maria Livia Del Giudice ◽  
Elisabetta Antonioli ◽  
Francesco Ghio ◽  
Enrico Orciuolo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Elderly Patients ◽  
Autologous Stem Cell Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Introduction: Currently, the regimen with bortezomib plus melphalan and prednisone (VMP) is a standard treatment for multiple myeloma and it is recommended as the first-line therapy for patients with multiple myeloma (MM) ineligible for high-dose chemotherapy with autologous stem-cell transplantation.Objectives: Participants of the clinical trial are highly selected populations; therefore, the aim of this study was to present observations from real practice that can provide important information for practitioners and to investigate clinical outcomes of VMP regimen in elderly patients with newly diagnosed MM.Patients and Methods: We retrospectively analyzed the data on the efficacy and survival parameters, such as overall survival (OS) and event-free survival (EFS), with attention to the effect of gender, age and International Staging System (ISS) stage, of VMP regimen in 164 patients with newly diagnosed MM not eligible for high-dose chemotherapy with autologous stem-cell transplantation (median age, 75 years; range, 60–86 years).Results: Patients aged 75 years or older constituted 50.6% of the study cohort. Frail patients were 10.36%, according to the clinical frailty scale of geriatric assessment (GA). A total of 1203 courses of VMP regimen (mainly VMP 1–29, 99.16 %) were administered. The median cumulative delivered dose of bortezomib was 46.8 mg/m2. The overall response rate (ORR), including all patients with a partial response or better, was 81.7% and the complete response rate (CRR) was 10.36 %. After a median 38.51 months of follow-up, the median overall survival (OS) was 34.33 months; the median event-free survival (EFS) after VMP and second-line therapy (mainly Rd, 56.31%) were 18.51 and 10.75 months, respectively. In the subgroup of patients with 75 years or older the median OS was 29.76 months; the median EFS after first and second-line therapy were 17.76 and 8.93 months, respectively. The hazard ratio for OS was 2.276 (p-value 0.046) and for EFS was 1.507 (p-value 0.055) for the ISS stage II and III group. Age and gender were not negative predictors of survival.Conclusions: VMP treatment is highly effective in the first-line therapy of elderly patients with multiple myeloma ineligible for HDT with auto-SCT.

scholarly journals AUTOLOGOUS STEM CELL TRANSPLANTATION FOR AGGRESSIVE LYMPHOMAS

2012 ◽  
Vol 4 (1) ◽  
pp. e2012075 ◽  
Author(s):  
Giuseppe Visani ◽  
Paola Picardi ◽  
Patrizia Tosi ◽  
Alessandro Isidori
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

The role of high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in the treatment armamentarium of aggressive B- and T-cell non-Hodgkin lymphoma (NHL) is still a matter of debate. In the pre-Rituximab era, the PARMA study demonstrated the superiority of HDT/ASCT over conventional salvage chemotherapy in chemosensitive, relapsed patients. Subsequently, HDT/ASCT has become a standard approach for relapsed NHL. With the advent of Rituximab in the landscape of NHL, transplantation as part of first-line therapy has been challenged. However, no benefit in terms of disease-free or overall survival of HDT/ASCT over standard therapy was shown when Rituximab was added to both arms. Moreover, the superiority of HDT/ASCT over conventional salvage therapy in patients relapsing from first-line therapy including Rituximab was not confirmed. From these disappointing results, novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity have been developed, with the aim of improving the outcome of HDT/ASCT in aggressive NHL.In T-cell lymphoma, few publications demonstrated that consolidation of complete remission with HDT/ASCT is safe and feasible. However, up to one-third of patients may never receive transplant, mostly due to progressive disease, and relapse still remains a major concern even after transplant.

Influence of First-Line Regimens on the Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 931-931 ◽  
Author(s):  
Bimalangshu R. Dey ◽  
Benjamin Cox ◽  
A. Jo Chien ◽  
Martin Caron ◽  
Steven L. McAfee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Hematopoietic Stem ◽  
Group 2 ◽  
Group 1

Abstract Randomized trials that incorporated high-dose chemotherapy (HDC) plus autologous hematopoietic stem-cell transplantation (Au-HSCT) into the early treatment of patients with newly diagnosed multiple myeloma demonstrated superior overall and event-free survival (EFS) in patients 65 years of age or younger, who received Au-HSCT, as compared with patients who received conventional chemotherapy. Based on these encouraging results, Au-HSCT is recommended for patients with myeloma as part of their initial treatment, and today, myeloma is the most common indication for HSCT in the world. All patients in these trials received four to six months of conventional chemotherapy prior to HDC and Au-HSCT. In practice, however, both in the community as well as in academic hospitals, patients are undergoing Au-HSCT after being treated with various first-line regimens, including chemotherapeutics, high-dose dexamethasone (HDex), immunomodulatory drugs such as thalidomide and recently, proteasome inhibitors. In this retrospective study, we examined the impact of first-line therapy on the outcomes following Au-HSCT. Our objective was to compare two treatment groups - chemotherapy versus non-chemotherapy, prior to Au-HSCT - with respect to survival after Au-HSCT. Between 1997 and 2004, 37 previously untreated evaluable patients with myeloma, received either chemotherapy (group 1, n=25; vincristine, adriamycin and dexamethasone (VAD), n=24; melphalan and prednisone (MP), n=1) or non-chemotherapy regimens (group 2, n=12; HDex, n=9; thalidomide plus HDex, n=3), then received HDC followed by cyclophosphamide plus granulocyte colony stimulating factor-mobilized HSCT. The median age of patients in group 1 was 58 (range, 44–73) years and in group 2 was 55 (range, 41–67) years; 22 patients in group 1 (88%) and 10 patients in group 2 (83%) had stage III disease; the median times from diagnosis to HSCT were 6 (range, 5–16) and 8 (range, 5–25) months, respectively, in groups 1 and 2. The rates of complete and near-complete response were 44% in group 1 and 42% in group 2; the rates of partial responses were also similar: 48% and 42% respectively. The median duration of EFS was 31 (range, 7–89) months, and the median overall survival (OS) was 55 (range, 12–98) months in group 1, as compared with group 2 where EFS and OS were 21 (range, 12–40) and 31 (range, 16–76) months, respectively. The EFS at 3 years was 44% in group 1 and 25% in group 2, and OS at 5 years was 32% in group 1 and 8% in group 2 (statistically not significant). In conclusion, patients with newly diagnosed myeloma, when treated with chemotherapy prior to Au-HSCT, may have long-term overall and EFS advantages, as compared with patients who are treated with first-line non-chemotherapy regimens. The reasons for the longer duration of response in the chemotherapy group despite similar response rates in the two groups are unknown, but may be due to more effective suppression of residual disease or non-specific damage to the marrow microenvironment, which is necessary for the growth of myeloma cells. Although, the difference in survival outcomes following Au-HSCT between the two groups did not achieve statistical significance, our results raise an important question regarding the “adequacy” of different first-line regimens prior to Au-HSCT, and therefore, justify the need for prospective randomized studies to evaluate optimal pre-AuHSCT induction therapy.

Bortezomib with HIG-Dose Dexamethasone as First Line Therapy in Patients with Multiple Myeloma Candidates to High-Dose Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3595-3595 ◽  
Author(s):  
Alessandro Corso ◽  
Luciana Barbarano ◽  
Silvia Mangiacavalli ◽  
Luigi Montalbetti ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
Light Chain ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: A phase II multi-center study was performed to investigate the efficacy of Bortezomib with high-dose dexamethasone (Vel-Dex) as induction therapy in multiple myeloma (MM) patients (pts) candidates to high-dose therapy. Methods: Patients were planned to receive 4 courses of Vel-Dex (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1–4 and 8–11 every 3 weeks), followed by 2 courses of DCEP 4 weeks apart with stem cell collection, and a single autologous transplant with melphalan 200 mg/m2. Patients were untreated, aged ≤65 years, with Durie-Salmon stage III, II, or I in progression. Criteria of response were: CR: negative serum/urine immunofixation with <5% bone marrow plasmacytosis (BMPC); nCR: positive serum/urine immunofixation with <5% BMPC; VGPR/PR: reduction of at least 90%/50% of serum/urine monoclonal component (MC), and of BMPC. Adverse events (AE) were graded by the NCI-CTC version 3.0. Mann-Whitney U test was used to correlate response and main prognostic parameters. Results: From March 2006 to June 2007, 52 out of the 54 planned pts entered the protocol. Patient characteristics at enrolment were: male/female 33/19; median age 57 years (37–65); IgG/IgA/light-chain 33/9/10 pts; stage III/II/I in progression 44/5/3 pts; ISS I/II/III 21/14/17 pts; cytogenetic analysis showed del 13 in 54%, t (4;14) in 15%. Thirty-nine of 52 enrolled pts are evaluable for efficacy and toxicity after 4 Vel-Dex courses. Six pts were withdrawn (3 for progression, 2 for toxicity, 1 patient withdrew informed consent). Overall response rate (ORR) was 85%, with 67% major responses (CR 33%, nCR 26%, VGPR 8%), PR 18%, stable disease 7%, progression 8%. No statistically significant correlation was found between response and either age, stage, ISS, or unfavorable cytogenetics. Friedman ANOVA (p=0.00001) and Wilcoxon Matched Pairs (p<.05) tests showed a statistically significant progressive decrease of serum MC after each Vel-Dex cycle. Urine MC and serum free light chain ratio showed a strikingly rapid reduction after the first course with no further statistically significant decrease during the following courses. Regarding toxicity, NCI grade 1 or 2 AE were: infection (19), constipation (16), peripheral neuropathy (13), diarrhea (9), gastritis (6), nausea (5). NCI grade 3 AE were: infection (9) with 5 varicella-zoster, peripheral neuropathy (4), cardiac arrhythmia (2). A single grade 4 AE (fatal sepsis) occurred. At the time of this analysis, 25 pts completed the stem cell mobilization phase. All pts collected adequate number of stem cells (median CD34+ cells 6.2x106/kg, range 3.5–18.0x106/kg, median number of collection procedures 1). Discussion: This study shows that Vel-Dex as first line therapy produces high response rates in MM pts (ORR 85%, major response 67%). Toxicity was generally predictable and manageable. Stem cells were successful harvested in all patients. Vel-Dex appears an effective and safe pre-transplant treatment for younger MM patients.

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