The Clinical Characteristics and Therapeutic Status of Multiple Myeloma in China- a 23 Years Retrospective Analysis in One Single Center.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4919-4919
Author(s):  
Lugui Qiu ◽  
Yu-jie Mai ◽  
Rei Li ◽  
Dehui Zou ◽  
Yafei Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Survival ◽  
Clinical Characteristics ◽  
Response Rates ◽  
Survival Duration ◽  
Treatment Results ◽  
Median Survival Duration ◽  
Overall Response

Abstract The clinical characteristics and treatment results of the multiple myeloma patients admitted to our hospital from January 1980 to December 2002 were retrospectively analyzed and compared in order to put forward a feasible therapeutic strategy for MM in China. Results: 1. Clinical characteristics (1) 432 cases with full follow-up statistics were analyzed. The median age was 57 years (20 to 80).The peak onset age were 50 to 60 years. The ratio of male to female was 2.35:1. (2) 81% patients had anemia(Hb<100 g/L) at diagnosis. The median proportion of tumor cells in the bone marrow was 0.38 (0.005–0.970). 72.1% with high β2-MG (>3mg/L), 60% of the patients had abnormities in X-rays. (3) M-protein peak was detected in 78.5% patients. IgG made up the majority in classification(48.1%), IgA (21.8%)and light-chain(20.5%)next to it. 144 patients were in stage IIIA(40%), and 87 cases in IIIB(24.1%)at first diagnosis. (4) The median survival duration was 27 months (1–137months). 2. Treatment results: 206 cases had integral therapeutic records in 432 patients. (1) 200 patients were administered with drugs therapy, and their 3-year and 5-year survival were 32.01% and 15.8% respectively. The OS, median survival, 3-year and 5-year survival in MP group(n=46) were 30.4%, 30 months, 21.96% and 13.2% respectively. 149 cases(72.3%)received multi-drug combined chemotherapy(CCT).The overall response was 50.3% and significant higher than that of MP group(P=0.01).While the median survival duration(30.5 months), 3-year and 5-year survival rates (35% and 16.7% respectively) were as same as MP group (P>0.05. (2). 38/200 cases (19%) were treated with interferon in combination with chemotherapy over 6 months. The overall response rates were 53.6%, and the median survival duration was 52 months, and presented an increased response(P=0.02)and a prolonged survival duration (P=0.0003) compared with the no interferon group(34.4%,27months respectively. (3)Thalidomide was administered to 29 cases(14.5%), including 5 who took it alone(2.5%). The overall response rates were 50.3%. (4) 6 patients received hematopoietic stem cell transplantation. 5 patients with autologous peripheral blood stem cell transplantation were alive averagely in 73±12.5 months by the end of the follow-up. Conclusion: 1) MM patients in China had poor prognostic characteristics except of younger age compared with the westerns, especially most patients were diagnosed at III phase with significant lower survival. 2) CCT yielded higher response rates but no longer duration of survival benefit than MP when used as treatment for MM. INF-a and Thalidomide could benefit MM by combination with chemotherapy. Among patients who are <60 years old with good performance, HSC could prolong survival duration.

Immunotherapy with Rituximab after Peripheral Blood Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5232-5232
Author(s):  
Celso Mitsushi Massumoto ◽  
Edilson Pinheiro Junior ◽  
Otávio C.G. Baiocchi ◽  
Ronald Pinheiro ◽  
Adelson Alves
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Clinical Characteristics ◽  
Residual Disease ◽  
High Dose

Abstract Introduction: autologous stem cell transplantation is a potentially curative or may augment the time to progression in Multiple Myeloma (MM) patients. The immunotherapy with rituximab may help control the minimal residual disease after high dose chemotherapy. Twenty percent (20%) of Multiple Myeloma patients express the CD20+ protein and can be target for immunotherapy. Objective: The aim of this study was to evaluate the use of rituximab after autologous stem cell transplantation for Multiple Myeloma. Patients and Methods: eight patients (4 male) with a median age of 53 (range 43–59) years diagnosed with MM. All of them had received at least one previous regimen were enrolled in the protocol study. All patients signed the consent form. Patients in relapse received a salvage regimen with C-VAD n=2 (cyclofosfamide 4 g/m2 e vincristine 0.4 mg/d (d 1–4), doxorrubicin 0.9 mg/m2 (d1-4) e dexametasone 40 mg (d1-4; 9-12; 17–22) or cyclofosfamide (1OO mg/kg, n=7) followed by stem cell harvesting. The preparative regimen was Busulfan 12 mg/kg and cyclofosfamide 120 mg/kg or Melphalan 200mg/m2. Rituximab at a dose of 375mg/m2 weekly x 4 was given every 6 months for 2 years after SCT. The clinical characteristics of the patients are shown on Table 1. Results: the median time to ANC and platelets engraftment was 11 (range 8–12) and 26 (range 17–35) days. Patients have been in CR at a median time of 11 months follow-up. Minor Rituximab-associated toxicities were seen:rigor, fever and short of breath that were controlled with acetaminophen and diphenidramine. Conclusion: the Rituximab given after autologous stem cell transplantation is safe in Multiple Myeloma patients and may prolong time to disease progression. A randomized study is required to evaluate the role of rituximab after ASCT. Table 1 - Clinical Characteristics of Patients Patients Age/gender Status Pre- BMT Status Post- BMT Salvage Tx Prep. regimen ANC/Platelets X1000 MM3/ml Follow-up (months) FRC 57/M PR PR C-VAD BU+MEL 12/28 EXPIRED MB 52/F CR1 CR1 C-VAD BU+MEL 12/60 EXPIRED AM 52/F PR PR C-VAD BU+MEL 9/26 EXPIRED IM 54/M PR CR Cyx2 BU+MEL 12/21 ALIVE GAD 50/F PR CR Cyx2 BU+MEL 12/35 ALIVE SCM 59/M CR CR Cyx2 BU+MEL 10/17 ALIVE MAD 63/F CR CR C-VAD MELPHALAN 12/25 ALIVE JFC 51/M CR CR C-VAD BU+MEL 12/18 ALIVE

Gemcitabine, Dexamethasone, and Cisplatin (GDP) Is An Effective and Well-Tolerated out-Patient Salvage Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (HL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 113-113
Author(s):  
Alden A. Moccia ◽  
Felicitas Hitz ◽  
Paul Hoskins ◽  
Richard Klasa ◽  
Maryse Power ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Salvage Therapy ◽  
Clinical Characteristics ◽  
Response Assessment ◽  
Response Rates ◽  
Salvage Regimen ◽  
Bulky Disease ◽  
First Relapse

Abstract Abstract 113 Introduction: DLBCL and HL represent highly curable lymphoid malignancies. Patients (pts) whose lymphoma is refractory to or relapses following initial therapy pose a significant therapeutic challenge. The goal of therapy is to proceed to a non-cross-resistant salvage regimen followed by high dose chemotherapy (HDC) and stem cell transplantation (SCT) for transplant eligible pts. The optimal choice of salvage therapy remains unknown. The combination of gemcitabine, dexamethasone and cisplatin (GDP) has been shown in phase II studies to induce high response rates with minimal toxicity (Baetz T, Ann Oncol, 2003; Crump M, Cancer, 2004). Based on these promising results, British Columbia Cancer Agency (BCCA) policy has recommended GDP as the preferred salvage regimen for pts with relapsed/refractory DLBCL and HL since 2002. Patients and Methods: We conducted a retrospective analysis using the BCCA Lymphoid Cancer Database and included all pts with relapsed/refractory DLBCL and HL who received GDP as salvage therapy between September 2002 and June 2010. Pts were treated with gemcitabine 1000 mg/m2 IV day 1,8; dexamethasone 40 mg PO days 1–4 and cisplatin 75 mg/m2 IV day 1, administered at 3 week intervals (2-3 cycles for transplant eligible patients and up to 6 cycles for non-transplant candidates). Primary endpoints were response rate, PFS (defined as the interval from the beginning of GDP to first progression, relapse or death from any cause) and OS. Results: 235 pts treated with GDP were identified; 152 and 83 pts with relapsed/refractory DLBCL and HL, respectively. Clinical characteristics at time of diagnosis for patients with DLBCL were: 68% male, 65% stage III/IV, 42% bulky disease ≥ 10 cm, 43% B-symptoms, 59% IPI 0–2, 41% IPI 3–5. Median age at time of GDP was 57 y (range 20–79 y). 57 pts (37%) had primary refractory disease to first-line R-CHOP; 144 (95%) were treated with GDP at first relapse/progression; median time from diagnosis to relapse after R-CHOP (excluding primary refractory pts) was 21 m (range 7–139 m). 30 pts (20%) received rituximab with GDP. Detailed radiologic response assessment following GDP(+/−R) was available for 82% pts with response rates as follows: 16% CR/CRu, 33% PR, 17% SD, 34% PD. 9 pts (6%) underwent HDC followed by allogeneic SCT and 57 pts (38%) underwent HDC followed by autologous SCT. With median follow-up of 24 m from start of GDP (range 0–84 m), 51 pts (34%) were alive and 101 pts (66%) have died (99 from lymphoma, 1 treatment toxicity during allogeneic SCT, 1 unrelated cause). 2-y PFS and OS were 21% and 28%, respectively. The 2-y PFS and OS for the subset of patients who underwent HDC/SCT were 36% and 47%, respectively. Clinical characteristics at diagnosis for the 83 pts with relapsed/refractory HL were: 55% male, 59% stage III/IV, 39% bulky disease ≥ 10 cm, 55% B-symptoms, 80% nodular sclerosis, 4% mixed cellularity, 2% nodular lymphocyte predominant, 2% lymphocyte depleted and 12% HL NOS. IPS variables were retrievable on 66% patients: 82% IPS ≤ 3 and 18% IPS ≥ 4. Median age at time of GDP was 31 y (range 17–73 y). 30 pts (36%) had primary refractory HL and 73 (88%) received GDP at first relapse/progression. Median time from diagnosis to relapse following ABVD-like therapy (excluding primary refractory pts) was 20 m (range 9–186 m). Detailed radiologic response assessment following GDP was available in 67% pts with response rates as follows: 7% CR/CRu, 64% PR, 13% SD, 16% PD. In total, 1 pt underwent HDC followed by allogeneic SCT and 69 pts (83%) proceeded to HDC and autologous SCT. With a median follow-up of 30 m from start of GDP (range 0–86 m), 70 pts (84%) were alive and 13 (16%) have died (all from HL). 2-y PFS and OS were 58% and 85%, respectively, and for the subset of pts who underwent HDC/SCT were 57% and 86%, respectively. Hospitalization rates due to complications during GDP were higher in patients with DLBCL than HL (20% vs 7%), likely reflecting differences in age and co-morbidities between the 2 cohorts. No failures of stem cell mobilization were recorded and the only toxic death was a consequence of HDC and allogeneic SCT. Conclusions: GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL. Outcomes appear to be comparable to those reported with more aggressive regimens. Results from an ongoing Canadian prospective trial comparing R-GDP to R-DHAP will help clarify the role of GDP in the treatment of relapsed/refractory DLBCL. Disclosures: Connors: Hoffmann-La Roche: Research Funding.

Real-World Data on Multiple Myeloma: A Prospective National Registry in Uruguay

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5614-5614
Author(s):  
Eloisa Riva ◽  
Virginia Bove ◽  
Fiorella Villano ◽  
Alejandro Noria ◽  
Paula Petruskevicius ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Cause Of Death ◽  
Real World ◽  
Clinical Characteristics ◽  
National Registry ◽  
New Drugs ◽  
First Line ◽  
Osteolytic Lesions

Abstract Introduction Uruguayan population is 3,4 million, mostly caucasian (88%). Life expectancy is 77 years. Cancer is the second cause of death and the estimated incidence of Multiple Myeloma (MM) is 120 cases/year. Its diagnosis and monitoring are standardized and feasible, available nationwide. Treatment with Bortezomib, Thalidomide and stem cell transplant are available for all patients, regardless of their health care provider. However, there is no accurate data on MM incidence, care, treatment-results or mortality. The Uruguayan National Myeloma Registry is designed to document current clinical characteristics of newly diagnosed MM, management and outcome in a real-world setting. This information will be useful to plan strategies to improve our local approach and follow-up of this disease, reducing problems derived from extrapolating data from other realities. Methods This prospective national registry will include all MM diagnosed between January 2012 and January 2015 in all institutions, public and private, nationwide. Smoldering MM are not included. Data collection started in October 2014 and is being obtained from medical and day hospital reports at each institution. Our database includes detailed data of clinical characteristics, laboratory, citogenetics and FISH, treatment indicated, disease-related and treatment-related adverse events, response to treatment at onset and relapses, and cause of death. Results Up to now, 163 patients have been included in the registry (45% coverage). Median age at diagnosis was 67 years (range 33-94 years), 43% younger than 66 years. Distribution according Ig subtype was: IgG 52%, IgA 27,5%, Light chains 17%, non-secretor 2,6% and IgM <1%. At diagnosis, most patients had advanced disease: 82% Durie-Salmon III, 49% ISS 3. Median bone marrow plasmacytosis was 33% and median serum monoclonal protein level was 2,14 g/dl (range 0 - 10,7 g/dl). Anemia (hemoglobin <10 g/dl) was detected in 67% of the patients; 70% had osteolytic lesions whereas impaired kidney function (serum creatinine > 2 mg/dl) was observed in 38% and hypercalcemia in 19,7% at the time of diagnosis. Conventional cytogenetic was performed in 66% (n=108) being normal in 78% and high-risk in 5,5%. Fluorescence in situ hybridization (FISH) for del17p, t(4;14) and t(14,16) was evaluated in 66%, being negative in 76% and positive in 24%. The characteristics of the patients are described in Table 1. First-line treatment included at least one of the new drugs in 94% of patients younger than 65 years and in 62% of those older than 65 years. Treatment regimens are shown in Figure 1. First-line response was available in 54% (n=88). Response rate (≥ PR) was 78%, VGPR+CR=51% and CR=19 %. Ten patients had stable disease at the end of treatment and 5 (5,7%) were relapsed-refractory MM. In ≤ 65 years, VGPR + CR was higher than in > 65 years (56% vs 33%). Suspension or dose reductions due to treatment-related toxicity were required more frequently in patients > 65 years (50% vs 20%). Neuropathy was the most common adverse effect reported (14%). Overall, 26% of patients received autologous stem cell transplantation (ASCT) after first line therapy; 46% in ≤ 65 years and 9% in > 65 years. After a median follow-up of 19 months, progression free survival (PFS) was 88,6% and overall survival (OS) 78,8% (82,9% in ≤ 65 years and 78,8% > 65 years). Discussion This first MM National Registry provides a thorough insight into the characteristics of MM patients in our country, which may become a useful instrument to improve MM care. With a 45% coverage, we show that MM is detected in advanced stage, with a high percentage of patients with impaired renal funcion. ASCT is indicated in a low percentage, particularly in those younger than 65 years; reasons for this should be addressed in future research. Longer follow-up is needed to address the impact of new drugs in survival. To the best of our knowledge there is no other MM registry of this kind ongoing in our region. This could become a suitable platform to share with other countries in order to perform high-quality population-based research on the field. Table 1. MM clinical characteristics at diagnosis ≤ 65 years (N=70) >65 years (N=93) Sex: F/M (%) 44/56 45/55 Age (median) 56 73 Creatinin >2 mg/dl (%) 44,9 33 Hemoglobin<10g/dl (%) 59,4 66,7 Calcium ≥11,5mg/dl (%) 13 9,7 Osteolytic lesions (%) 78 58 Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.

1995 ◽  
Vol 13 (9) ◽  
pp. 2354-2360 ◽  
Author(s):  
G P Browman ◽  
D Bergsagel ◽  
D Sicheri ◽  
S O'Reilly ◽  
K S Wilson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Maintenance Therapy ◽  
Median Survival ◽  
Clinical Stage ◽  
Response Duration ◽  
Self Report ◽  
Survival Duration ◽  
Median Survival Duration

PURPOSE To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. PATIENTS AND METHODS In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. RESULTS Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. CONCLUSION Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.

scholarly journals B Cell Maturation Antigen-Specific CAR T Cells for Relapsed or Refractory Multiple Myeloma: A Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3113-3113 ◽  
Author(s):  
Nico Gagelmann ◽  
Francis Ayuketang Ayuk ◽  
Djordje Atanackovic ◽  
Nicolaus Kroeger
Keyword(s):  
T Cells ◽  
T Cell ◽  
High Risk ◽  
Research Funding ◽  
Response Rates ◽  
Overall Response ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Background Cellular immunotherapies represent an enormously promising strategy for relapsed/refractory multiple myeloma (RRMM). Chimeric antigen receptor (CAR) T cells targeting B cell maturation antigen (BCMA) have shown impressive results in early-phase clinical studies. Here, we summarize the current body of evidence on the role of anti-BCMA CAR T cell therapy for RRMM. Methods We performed a systematic literature review to identify all publicly available prospective studies. We searched Medline, Cochrane trials registry, and www.clinicaltrials.gov. To include the most recent evidence, meeting abstracts from international hematology congresses were added. A conventional meta-analysis was conducted using meta and metafor packages in R statistical software. Pooled event rates and 95% confidence intervals (CIs) were calculated using the inverse variance method within a random-effects framework. Main efficacy outcomes were overall response, complete response (CR), and minimal residual disease (MRD). Furthermore, relapse rates, progression-free survival, and overall survival were evaluated. In terms of safety, outcomes were cytokine release syndrome (CRS), neurotoxicity, and hematologic toxic effects. Results Fifteen studies comprising a total of 285 patients with heavily pretreated RRMM were included in quantitative analyses. Patients received a median of seven prior treatment lines (such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, stem cell transplantation) which included autologous stem cell transplantation in 90% of patients. The median age of patients was 59 years and median follow-up duration ranged from 1.1 to 11.3 months. Most studies used 4-1BB (or CD137), a member of the TNF receptor superfamily, as an activation-induced T-cell costimulatory molecule. Most studies used fludarabine and cyclophosphamide for lymphodepletion while one study used busulfan and cyclophosphamide and one study used cyclophosphamide only. Most studies used the former Lee criteria for CRS grading. Anti-BCMA CAR T cells resulted in a pooled overall response of 82% (95% CI, 74-88%). The pooled proportion of CR in all evaluable patients was 36% (95% CI, 24-50%). Within responders, the pooled proportion of MRD negativity was 77% (95% CI, 67-85%). Higher dose levels of infused CAR+ cells were associated with higher overall response rates resulting in a pooled proportion of 88% (95% CI, 78-94%). In addition, peak CAR T cell expansion appeared to be associated with responses.The presence of high-risk cytogenetics appeared to be associated with lower overall response rates resulting in a pooled proportion of 68% (95% CI, 47-83%). The presence of extramedullary disease at time of infusion did not influence outcome and was associated with similar response rates compared with RRMM patients who did not have extramedullary disease, resulting in a pooled proportion of 78% (95% CI, 47-93%). The pooled relapse rate of all responders was 45% (95% CI, 27-64%) and the median progression-free survival was 10 months. In terms of overall survival, pooled survival rates were 84% (95% CI, 60-95%) at last follow-up (median, 11 months). In terms of safety, the pooled proportion of CRS of any grade was 69% (95% CI, 51-83%). Notably, the pooled proportions of CRS grades 3-4 and neurotoxicity were 15% (95% CI, 10-23%) and 18% (95% CI, 10-31%). Peak CAR T cell expansion appeared to be more likely in the setting of more severe CRS in three studies. Most hematologic toxic effects of grade 3 or higher were neutropenia (85%), thrombocytopenia (70%), and leukopenia (60%). Conclusion Anti-BCMA CAR T cells showed high response rates, even in high-risk features such as high-risk cytogenetics and extramedullary disease at time of CAR T cell infusion. Toxicity was manageable across all early-phase studies. However, almost half of the patients who achieved a response eventually relapsed. Larger studies with longer follow-up evaluating the association of response and survival are needed. Disclosures Ayuk: Novartis: Honoraria, Other: Advisory Board, Research Funding. Kroeger:Medac: Honoraria; Sanofi-Aventis: Honoraria; Neovii: Honoraria, Research Funding; Riemser: Research Funding; JAZZ: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; DKMS: Research Funding.

Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.

1995 ◽  
Vol 13 (4) ◽  
pp. 910-913 ◽  
Author(s):  
N M Bleehen ◽  
E S Newlands ◽  
S M Lee ◽  
N Thatcher ◽  
P Selby ◽  
...  
Keyword(s):  
Phase I ◽  
Total Dose ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Lung Metastases ◽  
Interleukin 2 ◽  
Survival Duration ◽  
Median Response ◽  
Median Survival Duration

PURPOSE Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies. PATIENTS AND METHODS Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course. Courses were repeated every 4 weeks and the dose was escalated to 200 mg/m2/d x 5 (total dose, 1 g/m2) after the first course if toxicity was acceptable. Patients were all chemotherapy-naive, except for two who had previously received interferon alfa and one who had received interleukin-2 (the latter patient had also received two phase I drugs some time previously). RESULTS A complete response (CR) was documented in three patients (all with lung metastases) and a partial response (PR) in nine patients (21% CR plus PR rate). Seven of 56 patients were not assessable for response because of early death or deterioration. The overall response rate excluding these patients is 12 of 49 (24%). The median response duration was 6 months (range, 2.5 to 22+). Toxicity of the regimen, which was mainly hematopoietic, was low. The median survival duration for all patients was 5.5 months (range, 0.5 to 29.5). For responders, the median survival duration was 14.5 months (range, 3 to 28+), with four patients still alive. CONCLUSION Temozolomide in the schedule used has as good activity in chemotherapy-naive metastatic melanoma as the other most active agents currently in use. Further studies of the drug on its own and in combination with other agents is recommended.

Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report.

1993 ◽  
Vol 11 (6) ◽  
pp. 1118-1123 ◽  
Author(s):  
A A Forastiere ◽  
M B Orringer ◽  
C Perez-Tamayo ◽  
S G Urba ◽  
M Zahurak
Keyword(s):  
Median Survival ◽  
Squamous Cell ◽  
Curative Resection ◽  
Survival Rates ◽  
Residual Tumor ◽  
Transhiatal Esophagectomy ◽  
Preoperative Chemoradiation ◽  
Survival Duration ◽  
Median Survival Duration

PURPOSE In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery.

Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 945-945
Author(s):  
Roland Fenk ◽  
Peter Schneider ◽  
Martin Kropff ◽  
Ali-Nuri Huenerlituerkoglu ◽  
Ulrich Steidl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Significant Difference

Abstract High-dose chemotherapy (HDT) improves the outcome of patients with multiple myeloma (MM) in comparison to conventional chemotherapy. Dose-escalating strategies including tandem HDT are currently evaluated to further improve remission rates and survival of patients. Therefore we conducted a randomized multicenter trial to compare an intensified conditioning regimen with the current standard high-dose melphalan. The primary study endpoint was response rate, with overall survival (OS), event-free survival (EFS) and toxicity analysed as secondary endpoints. Between 1997 and 1999 a total of 56 patients with stage II and III disease, who were matched for age (median 56 years), number of previous therapies (median time from diagnosis to transplant 7 months) and different risk factors (beta2-microglobulin, LDH, CRP, cytogentic abnormalities, chemoresistant disease, IgA-subtype, renal impairment), were randomized. All patients received 2 courses of oral idarubicine/dexamethasone and 2 courses of intravenous cyclophosphamide/adriamycine in combination with G-CSF followed by peripheral stem cell collection. Thirty patients were treated with melphalan 200mg/m2 (HD-M) whereas 26 patients received idarubicine 42mg/m2, melphalan 200mg/m2 and cyclophosphamide 120mg/kg (HD-IMC) followed by autologous blood stem cell transplantation. Acute toxicity was higher with HD-IMC, including 5 (20%) treatment-related deaths due to infections versus none (0%) in the HD-M group. This lead to early termination of the study. Severity of mucositis (grade III-IV 19 vs. 8 pts., p=0.001), CRP (20 vs. 7 mg/dl, p<0.001), days of fever (11 vs. 3, p<0.001), days with iv-antibiotics (13 vs. 4, p<0.001), number of erythrocyte-transfusions (6 vs. 2, p<0.001), number of platelet-transfusions (16 vs. 4, p<0.001) and days to granulocyte engraftment (18 vs. 11, p=0.007) were significantly higher after HD-IMC. After a follow-up of 5 years analysis restricted to patients surviving the first 30 days after HDT showed a trend to higher response rates (CR+vgPR: 47% (95%CI 24–72%) vs. 35% (95%CI 18–56%), PR 37% (95%CI 17–63%) vs. 48% (95%CI 29–68%) and time-to-progression (median 31 vs. 15 months, p=0.1) in the HD-IMC treatment arm in comparison to HD-M, but there was no significant difference in EFS and OS (median 22 vs. 30, p= 0.31 and 66 vs. 66 months, p=0.8, respectively). Univariate analysis demonstrated that LDH levels > 200 U/L (p=0.04) and chemoresistant disease (p=0.05) were a bad prognostic factor for EFS. Beta2-Microglobulin levels > 5mg/dl (p=0.01), abnormal conventional cytogenetics (p=0.02) and LDH levels > 200 U/L (p=0.03) were predictive for an inferior OS. In conclusion intensified conditioning for HDT had an intolerable high treatment-related mortality and did not improve EFS and OS in patients with multiple myeloma.

Combination of Bortezomib and Dexamethasone (VD) or Bortezomib, Adriamycine and Dexamethasone (PAD) Followed by High Dose Therapy and Peripheral Blood Stem Cell Transplantation in First-Line Treatment of T(4;14) Multiple Myeloma : a Prospective Study of the MAG Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3408-3408
Author(s):  
Lionel Karlin ◽  
David Ghez ◽  
Marie-Olivia Chandesris ◽  
Sylvain Choquet ◽  
Margaret Macro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood Stem Cell ◽  
Induction Treatment ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Blood Stem Cell Transplantation

Abstract Abstract 3408 Poster Board III-296 The t(4;14)(p16.3;q32), leading to the ectopic expression of two potential oncogenes, the Multiple Myeloma Set Gene (MMSET) and the Fibroblast Growth Factor 3 (FGFR3), is found in 15% of patients with multiple myeloma (MM) and is associated with a very poor prognosis. We previously shown in patients under 65 years of age that High Dose Therapy followed by Peripheral Blood Stem Cell Transplantation (HDT-PBSCT) provides a high response rate (RR) but a very short median relapse-free survival of only 11 months. In addition, relapses are often aggressive and chemoresistant. Thus, more effective regimen is urgently needed. We prospectively studied 23 t(4;14) MM patients treated with 3 or 4 cycles of a combination of Bortezomib and Dexamethasone (VD) (n=4) or of Bortezomib, Adriamycine and Dexamethasone (PAD) (n=19) as induction treatment before HDT-PBSCT (Melphalan 200 mg/m2). T(4;14) was detected using real time quantitative PCR searching for IGH/MMSET and FGFR3 transcripts. RR, event-free survival (EFS) and overall survival (OS) were evaluated. Median age at diagnosis was 51 years (range, 33-64). Isotype was IgA in 12 (52%) patients. All patients had stage II or III MM. An elevated serum β2m level (>3.5 mg/L) was found in 14 (61%) patients, and a low haemoglobin (Hb) level (<10 g/dL) in 10. Four presented with renal failure and 5 with hypercalcemia. Three (16%) of 19 patients had a t(4;14) without expression of FGFR3. After induction treatment with VD or PAD, PBSC were successfully harvested with granulocyte-colony stimulating factor only (n=15) or following a cycle of high-dose cyclophosphamide (n= 7). RR after induction treatment was complete response (CR) in 6 (26%) patients, very good partial response (VGPR) in 9 (39%), partial response (PR) in 3. Five patients had refractory or progressive disease (PD), including 1 who died before stem cell mobilization. RR after HDT was CR in 11 (48%), VGPR in 4 (17%) and PR in 4 (overall RR of 82%). Three had PD. With a median follow-up of 18 months (range, 3-32), 9 (39%) patients are alive without relapse, including 4 with a 19, 27, 30 and 32 months follow-up respectively. Twelve (52%) patients relapsed. Two patients died in the first month post HDT from PD. We found a median EFS and OS from initiation of therapy of 14.7 and 30.9 months respectively. EFS was not influenced by Hb and/or serum β2m level. However, we found a significantly longer OS in patients with low β2m (median non reached) as compared to patients with high β2m (median=23.1 months, p=0.04). These preliminary results illustrate the heterogeneity of this disease and indicate that some t(4;14) MM patients seem to benefit from bortezomib containing regimen as induction treatment before HDT in term of EFS and OS. A larger series with a longer median time of follow up will be presented. Disclosures: No relevant conflicts of interest to declare.

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