Bortezomib (Velcade) in the Treatment of Relapsed or Refractory Multiple Myeloma: Analysis of Safety and Efficacy of Bortezomib From Registry of Monoclonal Gammopathy of Czech Myeloma Group

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1872-1872
Author(s):  
Viera Sandecka ◽  
Ivan Spicka ◽  
Vladimir Maisnar ◽  
Tomas Pika ◽  
Evzen Gregora ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Czech Republic ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Median Number ◽  
Advisory Committees ◽  
The Czech Republic

Abstract Abstract 1872 Background: Bortezomib (Velcade) is one of the most effective treatment options in the treatment of relapsed or refractory multiple myeloma (RRMM). In the Czech Republic, it has been available since 2004. Registry of monoclonal gammopathy (RMG) of the Czech Myeloma Group contains information of more than 90% of patients in the Czech Republic treated with novel drugs.Aims: The aim of this retrospective analysis was to verify the therapeutic efficacy and safety of bortezomib in the treatment of RRMM in the Czech Republic. Methods: Before inclusion to RMG, all persons signed the informed consent form. In total, 1469 MM patients treated with bortezomib were evaluated from the RMG between June 2004 and December 2011.A total of 51.5% (750/1469) RRMM patients were analyzed with follow-up ≥6 months from the start of first administration of bortezomib. 30.6% (450/1469) patients with newly diagnosed MM were excluded from the analysis as well as 18.2% (267/1469) with a short follow-up. Evaluation of treatment response was performed according to the IMWG criteria. Median patient age was 65 years (range 33.9–88.1), median time since starting therapy was 21.5 months (range 6.1– 86.2), median number of previous treatments was 3.0 (range 1.0–8.0). In total, 92% (690/750) patients finished treatment of bortezomib (cycles length 21–28 days with application on days 1, 4, 8,11 or 1, (4), 8, 15 for frail patients). Median number of bortezomib cycles delivered was 6 (0.5–15.5). Results: Assessment of therapeutic response was possible in 92% (690/750) of treated patients. Overall response (ORR) in 57.5% (397/690) patients including 3% sCR, 8% CR, 20.3% VGPR, 26.2% PR. Stable disease was confirmed in 11.4% (79/690) patients and 22.5% (155/690) patients had progressive disease. In 50.1% of responders, first response (≥MR; defined as a ≥25% decrease in the serum MIg) occurred within the first cycle. At the second cycle, 24.2% of responders started to respond. Median time to progression (TTP) for all responders was 12.4 months. Median overall survival after starting bortezomib therapy (OS) was 32.3 months for all responders. Altogether, 692 adverse events (AEs) were documented. The most frequent AEs were: anemia in 62% of patients (462/750); severity of anemia was distributed as follows: 33.3% (250/750) cases of grade 1, 28.3% (212/750) cases of grade 2. Thrombocytopenia grade 3 and 4 was seen in 21.5% (161/750) of patients. Pre-existing peripheral neuropathy (PNP) grade 1–2 was presented in 25.1% (191/750) of patients at the start of bortezomib treatment. After treatment of bortezomib, PNP could be documented in 59.3% (445/750) cases with 16% (71/445) cases of grade 3 and 0.7% (3/445) cases of grade 4 PNP. In subanalysis, groups of patients were compared with relapsed patients who were treated with bortezomib in the second, third or greater-line of therapy. Among these three groups, there were significant differences in the evaluation of ORR (59.8% vs. 53.4% vs. 46.8%, p=0.022), as well as the sCR+CR was dependent on the number of previous treatment lines (15.6% vs 7.3% vs. 1.4%; p<0.001). Median TTP had similar dynamics (14.5 vs. 11.0 vs. 10.0 months; p= < 0.001). Altogether, 55.5% (416/750) of patients were pre-treated with thalidomide, while other patients were pre-treated with only conventional cytotoxic agens. Between these two groups we found differences in the achievement of treatment response: sCR+CR (8% vs. 14.1%; p =0.007), median TTP (11.0 vs. 15.0 months; p = 0.001) and median OS from the start of treatment with bortezomib (28.2 vs. 36.5 months; p = 0.001). Autologous stem cell transplantation after treatment with bortezomib was performed in 13.9% (104/750) of patients with positive effect on survival compared to patients without autologous stem cell transplantation (median OS 42.4 vs. 31.2 months; p = 0.007, median TTP 19.4 vs. 11.4 months; p <0.001). Conclusion: Our results show that bortezomib is one of the highly effective drugs for patients with RRMM. In current practice, the benefit (measured TTP) is 10–14 months, according to severity of the disease with a favorable impact on overall survival even in heavily pretreated patients. Implementation of autologous stem cell transplantation in relapsed disease following bortezomib treatment had a beneficial effect on overall survival. Acknowledgments: This work was supported by IGA NT 12130–4 and IGA NT 12215–4 grants. Disclosures: Maisnar: Janssen Cilag: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer (Schering): Honoraria. Hajek:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

Interest of Negative Minimal Residual Disease Estimated by Flow Cytofluorometry After Allogeneic Stem Cell Transplantation for B-Cell Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2547-2547
Author(s):  
Caroline Algrin ◽  
Magali Le Garff-Tavernier ◽  
Oumedaly Reman ◽  
Vincent Levy ◽  
Anne Huynh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Advisory Committees ◽  
Flow Cytofluorometry ◽  
Post Transplant

Abstract Abstract 2547 Introduction. Minimal residual disease (MRD) eradication in patients with chronic lymphocytic leukemia (CLL) treated by standard chemo-immunotherapy regimens correlates with improved outcome. However, there is limited information about the interest of negative MRD after allogeneic stem cell transplantation (allo-SCT). In this study we investigated whether blood phenotypic remission could impact post-transplant outcome in patients with CLL. Methods. We retrospectively included patients who underwent allo-SCT for CLL and with post-transplant MRD monitored by four or six-colour flow cytofluorometry in blood samples (sensitivity≥10−4). Prognostic impact was evaluated on overall survival (OS) and progression-free survival (PFS). Each of these parameters was evaluated according to the best response and to the 12 month-MRD status, using log-rank test. Results. Thirty-three patients from 4 hematology departments were included. Median age at transplant was 54 years (range, 41 to 66 years). The median number of prior chemotherapy regimens was 3 (range, 1 to 6) including autologous stem cell transplantation in 48% of the patients. Status at transplant was available in 27 patients and 11% of them had negative MRD, 26% haematological complete response (CR), 59.% partial response (PR) and 4% had refractory disease. Twenty-two patients (67%) received a reduced intensity conditionning regimen. Conditioning regimen included serotherapy (antithymoglobulin n = 10, alemtuzumab n = 1, rituximab n = 1) in 12 patients. Twenty-two patients (67%) were transplanted with HLA identical sibling donor. The median number of MRD evaluations after transplant was 5 (range, 1 to 23). Response to transplant: After transplant, 16 patients achieved negative MRD, 15 patients achieved haematological CR, 1 PR and 1 did not respond to transplant. Among the 16 patients with phenotypic remission, negativation of MDR was obtained before the cessation of immunosuppressive therapy for 15 of them (94%) and median time to negativation was 7 months (range, 2 to 20 months). In patients achieving phenotypic remission chronic GVHD rate was 75% versus 44% in patients with post-transplant detectable MRD. Post-transplant outcomes: With a median follow-up of 27 months, the 2-y OS and the 2-y PFS were respectively 84% and 53%. Cause of death (n = 8) was progression in 4 cases and transplant related mortality in 4 cases. Impact of phenotypic remission: The achievement of phenotypic remission (whatever the time of evaluation) correlates with better PFS: 2-y PFS was 85% in these patients versus 27% in the other patients (p = 0.012). Considering the 19 patients with MRD evaluation available at 12 months after transplant, 2-y PFS was 100% in 12-month-negative-MRD patients (n = 10) versus 17% in positive-MRD patients at that date (p = 0.003) No relapse was observed in the group of patients who achieved phenotypic remission at 12 months post-transplant (figure). Conclusion. These data suggest that achievement of post transplant negative MRD in patients with CLL is associated with a long-term control of the disease and better PFS. In our series, no relapse occurred in patients with negative MRD at 12 months post transplant. These results could lead to decrease immunotherapy and to administrate donor lymphocytes to patients with post-transplant persistent positive MRD. Disclosures: Leblond: ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4356-4356 ◽  
Author(s):  
Veronica Gonzalez De La Calle ◽  
Eduardo Sobejano ◽  
Julio Davila ◽  
Enrique M Ocio ◽  
Noemi Puig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
B Lymphocyte ◽  
Disease Stage ◽  
Advisory Committees

Abstract BACKGROUND High dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old). Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT. AIMS The goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM). METHODS We reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression. RESULTS 106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%). Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03). Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007). CONCLUSIONS The lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. Disclosures Ocio: Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Upfront Autologous Stem Cell Transplantation for Newly Diagnosed Elderly Multiple Myeloma (MM) Patients: A Prospective Multicenter Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1989-1989
Author(s):  
Laurent Garderet ◽  
Cyrille Touzeau ◽  
Anne-Marie Stoppa ◽  
Denis Caillot ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Introduction: Previous trials have shown that autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy in terms of remission rate and PFS in younger MM patients. Concerns about toxicity and potential efficacy of ASCT in older MM patients lead most centers to limit ASCT indications to patients aged <65 years. However, at the era of novel induction regimens, and because of better patient selection and supportive care, ASCT may prove to be a valid treatment option even in older MM patients. Therefore, some investigators are questioning the widely used 65 years age limit. Patients and Methods: We prospectively analyzed the outcomes of 56 consecutive MM patients who had received ASCT between September 2012 and September 2014 in 6 institutions in France (protocol ClinicalTrials.gov Identifier: NCT01671826). Patients were newly diagnosed MM. For induction therapy, all patients received a bortezomib-based induction regimen (VD, VTD, VCD, or VRD, 4 to 6 cycles) according to center's local guidelines. Mobilization was performed with G-CSF or G-CSF+cyclophosphamide and plerixafor whenever needed. High-dose chemotherapy consisted of either 140 mg/m2 or 200 mg/m2 Melphalan. A short two months consolidation phase post ASCT was allowed (lenalidomide-dexamethasone, VD, VTD, VCD or VRD). No maintenance treatment was given. Response, disease progression and relapse were defined according to the IMWG uniform response criteria. All patients signed an informed consent form according to the EBMT guidelines. Results: At time of diagnosis, median age was 67 (range, 64-74) years with 23% of patients being >70 years. There were 30 males and 26 females. The immunoglobulin subtype was IgG (n=29), IgA (n=15), light chain (n=10), other (n=2). The Salmon and Durie stage was III in 89% of cases (n=47), and the ISS score was I (n=18; 35%), II (n=19; 37%), III (n=14; 27%). Patients had high risk cytogenetics features (t(4;14) and/or del17p) in 9 cases (16%). 10% of patients had a serum creatinine level >176 micromol/L. None of the patients underwent hemodialysis. The Sorror comorbidity score was 0 (34), 1 (6), 2 (2), 3 (6), 6 (1), unknown (7). The median age at time of ASCT was 68 years, and the median time from diagnosis to ASCT was 5 months. In an intention to treat analysis, out of 56 patients, 6 patients could not proceed to ASCT because of an early infectious death (n=1), serious comorbidity (n=2), disease refractoriness to induction (n=1), and failure to collect an adequate PBSC graft (n=2). A median of 5.31x106/Kg CD34+ cells could be collected. Disease status at time of ASCT was: CR (n=12; 24%), VGPR (n=19; 38%), PR (n=17; 34%), and SD/non-responding (n=2; 4%). The conditioning regimen consisted of 140mg/m² melphalan in 18 cases (36%) and 200mg/m2 in 32 patients (64%). Moreover, 4 patients (8%) received a tandem ASCT. The median time for neutrophils and platelets engraftment was 12 days. The day-100 post ASCT non-relapse mortality was 0% and the 2-year NRM was 4.2% (95% CI:[0.3-18.3]). The overall response rate at day 100 was 96% (CR: 34%, VGPR: 47%, PR: 15%, SD/non-responsive: 4%). At 3 months post ASCT, 82% patients were able to receive the planned post ASCT consolidation treatment. After a median follow-up of 12 months, the estimated progression-free (PFS) and overall survival (OS) rates at 2 years were 76% (95%CI: [61.6-94.1]) and 88% (95%CI: [76.7-100]), respectively. The incidences of infectious complications post ASCT, and response rates were comparable between the two melphalan dose levels (p=0.28). However, in the univariate analysis, the 200 mg/m2 melphalan conditioning group showed a better OS rate compared to the 140 mg/m2 group (1-year OS: 100% vs. 67%; p=0.012). Conclusion: These prospective multicenter results indicate that ASCT is a safe and effective treatment modality for elderly, but fit MM patients at the era of novel induction agents. Of note, patients above age 70 did not experience a worse prognosis. Thus, age per se should not be used as an exclusion criterion for ASCT. Longer follow-up data will be presented, but these results already set the frame for a randomized comparison to the non-transplant approaches in this patients' subgroup. Disclosures Garderet: Bristol-Myers Squibb: Consultancy. Touzeau:AbbVie: Research Funding. Stoppa:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Karlin:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4574-4574
Author(s):  
Anna Waszczuk-Gajda ◽  
Junfeng Wang ◽  
Liesbeth C. de Wreede ◽  
Tiarlan Sirait ◽  
Zubeyde Nur Ozkurt ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
Safety And Efficacy

Introduction Multiple myeloma (MM) patients with renal impairment (RI), especially dialysis-dependent (DD) RI, have poorer outcomes than MM patients with normal renal function. Autologous stem cell transplantation (ASCT) is a treatment option, but there is concern at a perceived higher risk of complications which may be limiting consideration of the use of ASCT in this population. The evidence is inconsistent among studies and interpretation is complicated by heterogeneous datasets, some dating to before the availability of novel agents. Finally, the reversibility of RI following ASCT is an important prognostic factor for both survival and quality of life. Aim To evaluate the safety and efficacy of ASCT in MM patients with DD RI transplanted in EBMT centres between 1997 and 2017. Methods Baseline characteristics at diagnosis, patient treatment regimens and clinical outcomes were collected using standardised report forms. OS was defined as the period between the date of ASCT and the date of death or the date of last observation. PFS was defined as the period between the date of ASCT and date of progression/relapse or death of any causes or the date of the last observation. Cox proportional hazard regression analysis was applied to assess risk factors for progression and death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank test. P&lt;0.05 was judged as statistically significant. Results A total of 109,959 adult MM patients are registered in the EBMT database as having undergone ASCT between 1997 and 2017. We further analysed 118 DD MM patients who had a first ASCT during this period. The median (range) age was 57 (27-71) years. Seventy (59%) patients were males. Forty nine patients (49/94 patients, 52%) had Karnofsky score ≥90. One hundred and ten patients were treated with hemodialysis and eight with peritoneal dialysis. A total of 68 (58%) patients had Light Chain MM, 43 kappa and 25 Lambda. In first-line induction therapy, 47/76 (62%) patients received bortezomib-based regimens. Forty-four (37%) patients achieved at least VGPR pre-ASCT. The median time from diagnosis to ASCT was 0.7 years (0.3-4.9). Melphalan doses were as follows: 140 mg/m2 (n=55, 67%), 70-100 mg/m2 (n=15, 18%), and &gt;140 mg/m2 (n=12, 15%). The times to Neutrophil (&gt;0.5) and Platelet (&gt;20) engraftment were 12 (10-37) and 14 (4-128) days, respectively. The 30-day and 100-day transplant-related mortality (TRM) rates were 0.0% and 0.9%, respectively. ASCT was associated with a significant deepening of response (at least VGPR pre- vs post-ASCT: 36/93 (39%) vs 48/93 (52%), p &lt; 0.001). The median PFS was 37 months (95% CI: 24-43) and 5-year PFS was 31% (95% CI: 20-41). The median OS was 102 months (95% CI: 67-129). Five-year OS post-ASCT was 62% (52-72) and 10-year OS 36% (17-55). Thirty-one (26%) DD MM patients achieved dialysis independence. There were no differences in PFS or OS when comparing the 1997-2007 and 2008-2017 cohorts: 5-year PFS - 28% (6-49) vs 31% (19-43) (p=0.7) and 5-year OS - 61% (38-84) vs 63% (51-74) (p=0.9), respectively. On univariate analysis of factors affecting PFS, achievement of an Overall Response Rate (ORR) (CR+VGPR+PR vs. Other) pre-ASCT was associated with a lower risk (HR 0.467, p=0.032) and older age (&gt;55 years) with a higher risk (HR 1.786, p=0.035) of post-ASCT progression. Age higher than 55 (HR 2.033, 95%CI: 0.992 - 4.166, p=0.053) increased and achievement of at least VGPR pre-transplant (HR 0.494, 95%CI: 0.224 - 1.091, p=0.081, on the verge of statistical significance) decreased the risk of death. Conclusion To the best of our knowledge, the DIADEM study is the largest analysis of ASCT in DD MM pts to date. This cohort of 118 unselected patients had an OS comparable to patients without RI. This may reflect patient selection based on younger age, Karnofsky scores and pre-ASCT response. The low TRM and excellent outcomes support consideration of the use of ASCT in pts with DD RI. Notably, more than a quarter of patients became dialysis independent, an outcome likely to confer an improved Quality-of-Life.. These results can also inform the debate around the role of renal transplantation in younger DD MM patients who do not achieve dialysis independence. Disclosures Snowden: IDMC: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Mallinckrodt: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Dreger:MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; Neovii, Riemser: Research Funding. Illés:Takeda, Seattle: Research Funding; Janssen, Celgene, Novartis, Takeda, Roche, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Basak:Teva: Honoraria; Celgene: Honoraria. Gyan:Pfizer: Honoraria. Hayden:Alnylam: Honoraria; Amgen: Honoraria. Beksac:Amgen: Consultancy; Celgene: Consultancy; Janssen&Janssen: Consultancy; Takeda: Consultancy. Schönland:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Management of Relapsed/Refractory Hodgkin Lymphomas After ASCT in Czech Republic.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4357-4357
Author(s):  
Heidi Mocikova ◽  
Robert Pytlik ◽  
Ludek Raida ◽  
Pavel Zak ◽  
Jana Markova ◽  
...  
Keyword(s):  
Stem Cell ◽  
Czech Republic ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Survival ◽  
Research Funding ◽  
Salvage Treatment ◽  
Advisory Committees ◽  
The Difference

Abstract Abstract 4357 Background This retrospective study evaluates outcomes of patients (pts) treated with autologous stem cell transplantation (ASCT) and subsequent therapy for relapsed/refractory Hodgkin lymphoma (HL) who underwent ASCT in 7 transplant centres in Czech Republic. Patients and methods 194 pts with relapsed/refractory HL treated with ASCT (184 single, 10 tandem) between 01/2000 and 06/2009 were analyzed. Overall survival (OS) and progression-free survival (PFS) since the time of ASCT were evaluated according to Kaplan-Meier methods. Outcome of pts relapsing after ASCT was evaluated since the time of relapse. Different salvage modalities after ASCT and their impact on survival were compared with log-rank test. Results Median age of pts at time of ASCT was 33 (range 18-66) years. Best response observed after ASCT: complete remission (CR) in 124 pts (64%), partial remission (PR) in 35 pts (18%), stable disease (SD) in 2 pts (1%) and relapse/ progression in 33 pts (17%). Median follow-up was 44 months (m)(range, 3-108). Projected 5-year OS was 71% (median not reached) and PFS 54% (median 86m). Overall 70 pts progressed/relapsed after ASCT and allogeneic stem cell transplantation (alloSCT) was planned in 38 of them, but carried out only in 25 pts (3 myeloablative and 22 reduced intensity regimens). 37 pts were scheduled for other salvage therapy, 4 pts underwent second ASCT and 4 pts did not receive further treatment. Median survival of 70 pts since relapse after ASCT was 16.9 months. Median survival since relapse after ASCT in pts with or without alloSCT was 31.8 and 12.4 months respectively, but the difference was not statistically significant. Overall 51/194 (26.3%) pts died. 11 of 124 pts died in continuous remission after ASCT due to non-relapse mortality including transplant related mortality in 8pts (6.4%). 40/70 relapsed/refractory pts died: 29 in relapse/progression (20 after salvage treatment, 9 after alloSCT) and 11 pts due to non-relapse mortality (5 after salvage treatment and 6 after alloSCT). Conclusion Efficacy of ASCT was confirmed in 113/194 surviving pts (58%) in continuous remission. Median survival of relapsed pts following ASCT was 16.9 m. AlloSCT seems to improve survival in relapsed/refractory patients, although the difference is not statistically significant. New drugs should be offered to patients failing transplantation treatment. Disclosures: Trneny: GSK: Consultancy; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fresenius: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Bortezomib- and Thalidomide-Induced Peripheral Neuropathy (PN) in Multiple Myeloma (MM): Clinical and Molecular Analysis of 474 Patients Treated with Thalidomide-Dexamethasone (TD) or Bortezomib-TD (VTD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1821-1821
Author(s):  
Paola Tacchetti ◽  
Carolina Terragna ◽  
Gioacchino Catania ◽  
Magda Marcatti ◽  
Andrea Nozza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Complete Resolution ◽  
Study Endpoint ◽  
Consolidation Therapy ◽  
Advisory Committees

Abstract Abstract 1821 Introduction: PN is an important complication of MM and its incidence has been further increased after the introduction of the novel agents thalidomide and bortezomib. In a phase 3 trial comparing TD with VTD as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation for previously untreated MM patients, the VTD arm was significantly superior over TD in terms of improved rates of complete or near-complete response (CR/nCR) (the primary study endpoint) and progression free survival (PFS). Toxicity of VTD and TD regimens, including PN, was a secondary study endpoint. Methods: We performed a subanalysis of the study to assess the frequency, reversibility, risk factors and molecular markers associated with treatment-emergent PN. PN was graded by use of National Cancer Institute's Common Toxicity Criteria (NCI CTCAE) version 3.0. Since grade 1 PN could be misinterpreted and does not interfere with the daily activities, only patients who developed PN of at least grade 2 were evaluated. A total of 474 patients (of whom, 236 randomized to the VTD arm and 238 to TD) were stratified according to the development or not of grade ≥2 neurological adverse events (NAEs). Gene expression profiles (GEP) of pre-treatment CD138+ bone marrow plasma cells (BMPCs) were analyzed in a subset of 127 VTD-treated patients for whom biological samples taken at diagnosis were adequate for genomic analysis. GEP experiments were performed using the Affymetrix HG-U133 Plus 2.0 platform and class comparison of groups of array was done with one-way ANOVA Partek Genomic Suite (version 6.4). Results: Occurrence of PN throughout the entire treatment program was significantly higher in the VTD arm compared with TD. In particular, the rate of grade ≥2 PN was 35% vs 10% (p<0.001), and grade ≥3 was 15% vs 2.5% (p<0.001), respectively. Most of NAEs occurred during the induction phase (52% in VTD and 70% in TD arms), while a minority were seen during consolidation therapy (6% in VTD and 8% in TD). Median time to onset of grade ≥2 PN was 83 days in the VTD arm compared with 37.5 days in TD arm (p=0.04). Overall, 89% of patients on VTD and 95% on TD had a complete resolution of PN within a median of 70 and 61 days (p=0.6), respectively. An improvement to at least grade 1 was recorded in 94% of patients in the VTD arm and in 95% on TD within a median of 78.5 and 61 days (p=0.4), respectively. Three patients (1%) on VTD and none on TD discontinued treatment due to neurological toxicity. Notably, development of grade ≥2 PN did not affect the rates of CR/nCR, and both time to progression (TTP) and PFS. By univariate analysis, characteristics of patients at baseline, including age, MM isotype, ISS stage and cytogenetic abnormalities such as del(13q), t(4;14) or del(17p), did not influence the development of grade ≥2 PN in both arms. GEP were analyzed in 127 patients assigned to the VTD arm (44 with and 83 without treatment-emergent grade ≥2 PN). Patients experiencing a grade ≥2 PN were characterized by the differential expression of 184 genes (p<0.01). The genes showing the highest change in expression included NRN1 (involved in the axonal regeneration), GSTM1 (involved in the detoxification of electrophilic compounds by conjugation with glutathione), DCTN1 (whose mutations are associated in specific types of disease-associated axonal degeneration). GeneGO® pathway analysis of differentially expressed genes showed enrichment for genes mainly implicated in the regulation of cytoskeleton rearrangement and the axonal guidance: indeed, several genes, which are involved in the signal transfer from semaphorin and ephrin to the cytoskeletal and motor proteins resulted differentially expressed in patients who developed grade ≥2 PN (SEMA6A, SEMA4B, ACTA2, EPHA5, NEB). Conclusions: Although VTD incorporated into double ASCT was associated with a higher incidence of grade ≥2 PN compared with TD, the probability of complete resolution or improvement to at least grade 1 was comparable in both VTD- and TD-treated groups. Importantly, NAEs did not adversely affect the rate of CR/nCR, and TTP and PFS. No relationship between development of PN and both patient demographics and disease characteristics was observed. Conversely, GEP analysis of BMPCs from patients with VTD-induced PN showed the significant deregulated expression of genes involved in the nervous system function. Disclosures: Off Label Use: Bortezomib and Thalidomide as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation in newly diagnosed multiple myeloma. Tosi:Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Baccarani:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Mayers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Cavo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Impact of Complete Response on Survival with Either Autologous Stem Cell Transplantation or Conventional Chemotherapy: Results of a Pooled Analysis of 5 Phase III Trials in Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 927-927
Author(s):  
Roberto Mina ◽  
Alessandra Larocca ◽  
Massimo Offidani ◽  
Sara Bringhen ◽  
Tommaso Caravita ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Iii ◽  
Conventional Chemotherapy ◽  
Advisory Committees ◽  
The Impact

Abstract Introduction The introduction of novel agents in the treatment of Multiple Myeloma (MM) led to a significant improvement in the quality of response, increasing the number of patients able to achieve a complete response (CR). Several studies showed that the achievement of CR improved survival, both in young and elderly patients with newly diagnosed MM (NDMM). In this study we investigated the impact of CR on survival obtained with either autologous stem cell transplantation or conventional chemotherapy in NDMM patients. Patients and Methods Data from NDMM patientsenrolled in 5 phase III Italian trials were analysed. Three trials included patients eligible for autologous stem cell transplantation (ASCT): RV-MM-209 (melphalan-prednisone-lenalidomide [MPR] vs high-dose melphalan [Mel200] and ASCT, followed by lenalidomide maintenance vs no maintenance), RV-MM-EMN-441 (cyclophosphamide-lenalidomide-dexamethasone vs Mel200-ASCT, followed by lenalidomide [R] versus lenalidomide-prednisone [RP] maintenance) and MM-BO2005 (bortezomib-thalidomide-dexamethasone vs thalidomide-dexamethasone as induction/consolidation, followed by dexamethasone maintenance). The two remaining studies included elderly patients ineligible for ASCT: GIMEMA-MM0305 (bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance vs bortezomib-melphalan-prednisone) and EMN01 (MPR vs cyclophosphamide-prednisone-lenalidomide vs lenalidomide-dexamethasone, followed by R vs RP maintenance). The primary objective of the study was the evaluation of the impact of CR on overall-survival (OS) and progression-free survival (PFS) and its relationship with age (young vs elderly patients) and type of treatment (ASCT vs conventional chemotherapy [CC])). Univariate and multivariate analyses of OS and PFS, including ISS, ASCT and type of novel agents used as induction treatment, were performed. Response was treated as a time-dependent variable. A landmark analysis was performed. Results 2439 NDMM patients were evaluated; the best response was available in 2359 patients. 656 patients achieved a CR or better, whereas 1353 patients achieved a very good partial response (VGPR) or a partial response (PR), and were included in the analysis. After a median follow-up of 44 months, the 5-year OS was 75% in CR patients as compared with 60% in VGPR/PR patients (HR 0.49, p<0.001), and 5-year PFS was 44% and 22% (HR 0.44, p<0.001), respectively. Among CR patients, 383 were treated with ASCT and 273 with CC. A trend towards a better 5-year OS was reported in the ASCT group as compared with the CC group (79% vs 69%; HR 0.6, p=0.09; Figure 1). A significant PFS advantage was observed among CR patients treated with ASCT in comparison with those who received CC (median, 59 vs 47 months; HR 0.54, p=0.008; Figure 2). No significant differences were observed between young and elderly CR patients treated with CC in terms of 5-year PFS (43% vs 41%; HR 0.9, p=0.5) and 5-year OS (73% vs 69%; HR 1.07, p=0.8). In the multivariate analysis, ASCT confirmed to be an independent predictor of prolonged PFS in CR patients, with a trend towards longer OS, in comparison with CC. Conclusions ASCT induced deeper CR that translated into prolonged PFS and OS as compared with CC. No differences were noticed between young and elderly patients achieving a CR with CC. Disclosures Off Label Use: Use off-label of drugs for the dose and/or schedule and/or association. Larocca:Janssen-Cilag, Celgene: Honoraria. Offidani:Janssen-Cilag, Celgene, Sanofi, Amgen, Mundipharma: Honoraria. Bringhen:Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; Janssen-Cilag, Celgene, Novartis: Honoraria. Caravita:Celgene: Honoraria. Di Raimondo:Janssen-Cilag, Celgene: Honoraria. Gaidano:Celgene: Research Funding; Morphosys, Roche, Novartis, GlaxoSmith Kline, Amgen, Janssen, Karyopharm: Honoraria, Other: Advisory Boards. Petrucci:Celgene, Janssen-Cilag, Sanofi, Bristol-Myers Squibb: Honoraria. Ria:Italfarmaco: Honoraria; Novartis: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria. Hajek:Celgene, Amgen: Consultancy, Honoraria; Janssen-Cilag: Honoraria. Cavo:Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Novartis, Sanofi Aventis: Honoraria; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria.

Prognostic Impact of Cytogenetic Abnormalities On Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated with Thalidomide-Dexamethasone Incorporated Into Double Autologous Stem-Cell Transplantation: An Analysis of 593 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3562-3562 ◽  
Author(s):  
Elena Zamagni ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Paola Tacchetti ◽  
Mauro Fiacchini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Impact ◽  
Advisory Committees ◽  
Cytogenetic Abnormalities ◽  
Cox Regression Analysis

Abstract Abstract 3562 Aim of the present study was to evaluate the clinical outcome of a large series of younger patients with symptomatic multiple myeloma (MM) who were enrolled in two subsequent clinical trials of thalidomide-dexamethasone (thal-dex) incorporated into double autologous stem-cell transplantation (ASCT) to support high-dose melphalan (200 mg/m2). In both studies, thal (100 mg/day for the first 14 days and then 200 mg/day) and pulsed dex (between 480 and 160 mg per cycle), were administered from the onset until the second ASCT. The analysis was performed on an intention-to-treat basis on a total of 593 patients who were followed for a median of 36 months. The best VGPR and CR rates were 69% and 35%, respectively. The median duration of CR was 66 months. Median TTP and PFS were 53 and 44 months, respectively. The 5-year projected rates of TTP and PFS were 46% and 38%, respectively, while the corresponding value for OS was 67%. More than 80% of the patients were screened at diagnosis for the presence of cytogenetic abnormalities by FISH analysis. Forty-five percent of patients had del(13q), while t(4;14) and del(17p) were found in 16 % and 7 % of patients, respectively. The presence of del(17p) and/or t(4;14) was associated with a significantly shorter 5-year projected TTP, PFS and OS in comparison with the absence of these abnormalities, indifferently from the presence or absence of del(13q) (TTP: 30% vs 53%, respectively P=0.0000; PFS: 28% vs 45%, respectively, P=0.0000; OS: 53% vs 69%, respectively, P=0.0000). OS and PFS curves of patients carrying del(13q) alone were almost superimposable to those of patients without cytogenetic abnormalities, while TTP was significantly shorter for patients with del(13q) alone (5-year projected rates: 40% vs 53%, respectively, P=0.04). Patients carrying del(17p) in the absence of t(4;14) had similar 5-year projected TTP and PFS as compared with t(4;14) positive but del(17p) negative patients. However, OS was significantly shorter for the subgroup with del(17p) and absence of t(4;14) in comparison with that of patients carrying t(4;14) without del(17p) (5 year projected rates: 18% vs 70%, respectively, P=0.03). In a multivariate analysis, presence of del(17p) and high beta2-m at baseline were the most important variables adversely influencing TTP (HR: 2.3, P=0.001 and HR: 1.8, P=0.002, respectively), PFS (HR: 2.0, P=0.001 and HR: 1.9, P=0.001, respectively), and OS (HR: 3.9, P=0.000 and HR: 2.0, P=0.005, respectively). Additional variables predicting for shorter TTP and PFS were the presence of t(4;14) (HR: 1.8, P=0.004) and of del(13q) (HR: 1.6, P= 0.009). Also the quality of best response to the overall treatment program influenced clinical outcomes. In particular, patients achieving CR had a significantly longer PFS and OS than those achieving a VGPR (PFS: median 68 vs 40 months, respectively, P=0.007; 5-year projected OS rates: 84% vs 70%, respectively, P=0.01). In conclusion, incorporation of thal-dex into double autotransplantation failed to overcome the poor prognosis conferred by del(13 q), t(4;14) and del(17p). In a multivariate Cox regression analysis, del(17p) and high levels of serum beta2-m at diagnosis were the strongest variables adversely influencing PFS and OS. In comparison with the presence of t(4;14) but absence of del(17p), patients carrying del(17p) without t(4;14) had a significantly shorter OS, possibly due to their worst outcome after relapse. Presence of del(13q) alone conferred a significantly shorter TTP, but did not have an adverse impact on OS due to the favorable role of effective salvage therapies incorporating either bortezomib or lenalidomide. Disclosures: Off Label Use: use of first line thalidomide in preparation for ASCT. Cavo:Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, no; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no.

Modified High-Dose Melphalan and Autologous Stem Cell Transplantation (mHDM/SCT) In the Treatment of AL Amyloidosis (AL) and/or High-Risk Myeloma (hM): Analysis of SWOG Trial S0115

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2004-2004
Author(s):  
Vaishali Sanchorawala ◽  
Antje Hoering ◽  
David C Seldin ◽  
Kathleen T Finn ◽  
Salli A Fennessey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
High Dose ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
High Dose Melphalan

Abstract Abstract 2004 Treatment of AL amyloidosis (AL) and myeloma (M) with high dose melphalan and autologous stem cell transplantation (HDM/SCT) is effective in inducing hematologic remissions and improving survival. However, the benefit of HDM/SCT in AL and host-based high-risk myeloma (hM) has not been explored in a multi-center study. We designed a trial of two cycles of modified high dose melphalan at 100 mg/m2 and autologous stem cell transplantation (mHDM/SCT) through SWOG 0115 (ClinicalTrials.govIdentifier: NCT00064337). The primary objective was to evaluate overall survival and additional objectives were to determine hematologic responses and tolerability of two cycles of mHDM/SCT in AL and hM in a multicenter study. Eligibility for patients with AL required evidence of tissue diagnosis of amyloidosis, underlying associated plasma cell dyscrasia, and adequate measures of performance status (Zubrod 0–2) and cardiopulmonary function (LVEF >45%, DLCO >50%). Eligibility for hM patients required age >70 years and/or serum creatinine of >2 mg/dL or calculated creatinine clearance of <50 mL/kg/min. Peripheral blood stem cells were collected following G-CSF alone with minimum yield of 7.0×106 CD34+ cells/kg required for participation in the trial. From 1/2004 to 11/2010, 70 eligible patients with AL (61 with AL and 9 with myeloma associated AL) and 27 with hM were enrolled at 17 centers in the US. The median age was 64 years (range; 33–79) and M:F ratio was 1.6:1. The median number of organs involved was 2 (range, 1–8). There were 22 patients (31%) with cardiac involvement. The median serum creatinine level was 1.7 mg/dL (range, 0.6–10.0) for patients with hM. There are 68 patients with AL and 25 patients with hM eligible for survival and 67 patients with AL and 25 patients with hM eligible for adverse event analysis at this time. The treatment-related mortality (TRM), defined as deaths within 100 days of registration (even without protocol-directed treatment) was 9% (n=9/97). TRM was 10% (n=7/70) for AL and 7% (n=2/27) for hM. TRM was 14% (n=3/22) for patients with AL and cardiac involvement. Grade 3 and higher non-hematologic adverse events by CTCAEv3.0 were experienced by 75% (n=50/67) of AL patients and 80% (n=20/25) of hM patients. The median overall survival is 68 months for AL with a median follow up for surviving patients of 40.6 months (range; 1.2–79). The median survival for hM patients has not been reached yet with a median follow-up of 34 months. The 5-year survival is 55% for AL and 54% for hM patients; and the median progression-free-survival is 43 months for AL and 31 months for hM. Hematologic responses, defined by the standard consensus criteria, were achieved by 39% (n=11/28) evaluable patients for AL and 57% (n=4/7) for hM following SCT. Clinical and organ responses were also evident at 1 year following HDM/SCT. Thirty % (n=3/10) patients with AL experienced cardiac response. In conclusion, this experience demonstrates that with careful selection of patients, mHDM for SCT in patients with AL amyloidosis and hM, even in the setting of a multicenter study, can lead to prolonged overall survival with acceptable TRM and morbidity. Disclosures: Holmberg: Celgene: Research Funding; Millennium-Takeda: Research Funding; Otsuka: Research Funding; Seattle Genetics: Research Funding; Genzyme: Research Funding; Genzyme: Research Funding; Merck: Research Funding; Genzyme: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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