A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma.

1984 ◽  
Vol 2 (7) ◽  
pp. 836-840 ◽  
Author(s):  
S Pavlovsky ◽  
J Saslavsky ◽  
M Tezanos Pinto ◽  
L Palmer ◽  
M Curuchet ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Prognostic Factors ◽  
Partial Response ◽  
Randomized Trial ◽  
Survival Time ◽  
Creatinine Level ◽  
Response Rate ◽  
Randomized Study ◽  
Significant Difference

In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.

Clinical Experience and Prognostic Factors with Bortezomib-Combined Regimen in 40 Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5211-5211
Author(s):  
Juan Li ◽  
Ying Zhao
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Prognostic Factors ◽  
Adverse Effects ◽  
Light Chain ◽  
Response Rate ◽  
Total Response ◽  
Light Chain Type ◽  
Total Response Rate ◽  
Chain Type

Abstract To explore the medical effects, prognostic factors relating to the effects and side effects of bortezomib-combined regimen in treatment of multiple myeloma (MM), and evaluate the safety of this regimen in patients with special conditions. Methods: Forty newly diagnosed and relapsed or refractory MM treated with the regimen of combination of bortezomib and dexamethasone in a cycle of 3 weeks. All of the patients received a median of 3 (1–9) cycles of the treatment. Response to bortezomib was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT) and adverse events were graded according to the National Cancer Institute Common Toxicity Criteria. Results: Total response rate was 75.0% (30/40), and the rate of CR+nCR was 42.5% (17/40). Eighty percent patients (24/30) showed effects after the first cycle, although the median time of best effect was 2 cycles. Compare to the other types, light-chain type had higher total response rate (100.0% vs. 65.5%, P=0.038)and CR rate (36.4% vs. 6.9%, P=0.039), and also responded earlier with 81.8% (9/11) patients reached the best effect after the first cycle. The factors which showed no relationship to the effects were age (<65 years vs. >65 years, P=0.081), sex (P=0.696), DS staging (P=1.0), ISS staging(P=0.969), newly or retreated (P=0.731), using thalidomide or not(P=0.338), renal function damage or not(P=0.401), PLT level(P=1.0), hypercalcemia or not(P=0.306), Hb level(P=0.70)and the ratio of tumor cells in bone marrow(P=0.693). Grade III~IV adverse effects in this VD regimen was low, including leucocytopenia, thrombocytopenia, diarrh ea and debility, could be relieved by symptomatic treatment or delay the chemotherapy. The rate of infection was high and which was one of the important cause of death. Renal function improvement could be showed in all of the 10 patients who had renal inadequacy, and compared with normal patients, the incidences of side and adverse effects had no statistical differences. Conclusion: The Bortezomib combination regimen has significant effect in MM treatment. It shows more significant in light-chain type patients, and show earlier effect onset. This regimen can be tolerant in most patients, and is also safe in patients with renal inadequacy.

scholarly journals Efficacy of Bortezomib plus dexamethasone as a first line treatment in newly diagnosed cases of Multiple Myeloma: A Single Centre Study in a Tertiary Care Hospital

2020 ◽  
Vol 28 (1) ◽  
pp. 34-41
Author(s):  
Mahbuba Sharmin ◽  
Mohammad Manirul Islam ◽  
Abdul Aziz ◽  
Salauddin Shah ◽  
Md Jalilur Rahman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Intracranial Haemorrhage ◽  
Response Rate ◽  
Malignant Tumors ◽  
Tertiary Care ◽  
Care Hospital ◽  
Newly Diagnosed ◽  
Overall Response ◽  
Highly Effective

Background: Multiple Myeloma (MM) accounts for 1% of malignant tumors and 10%–15% of hematopoietic neoplasms. Bortezomib, a first in class proteasome inhibitor, induces apoptosis and growth arrest and reverse chemoresistence in Myeloma cell and has demonstrated no irreversible adverse effect on haemopoietic stem cell. Dexamethasone increases the response rate. Thus, Bortezomib plus dexamethasone represent highly effective regimen for previously untreated Multiple Myeloma cases and significantly higher response rates approximately 70%– 90% have been observed.This combination thus may serve the basis of future strands of care in Multiple Myeloma patients. Objective: The aim of the study was to assess the efficacy , safety and tolerability of Bortezomib in newly diagnosed cases of Multiple Myeloma patients in Bangladesh. Materials & Methods: This prospective observational study was carried out in the Haematology department of BSMMU from June 2017 to December 2018. Patients received inj. Bortezomib (1.3mg/m2 ) 4 cycles as an intravenous bolus on days 1,4,8,11 in a three week cycle (twice weekly administration) in indoor and same patients as day care basis in outpatients department. Dexamethasone at 40 mg was given intravenously or orally on the day of and day after inj Bortezomib.A self administered questionnaire containing different set of questions regarding Multiple Myeloma were used for data collection. Results: Among the study population, 93% of patients had anaemia followed by bone pain (86%) and renal impairment (39%). Out of 25 patients,complete response achieved in 13 patients (52%), where 4 patients(16%) showed partial response,6 (24%) showed very good partial response and 2 (8%) patients showed no response. The overall response rate was 92% belonged to partial,very goofd partial and no respone respectively. Death occurred in 3 cases (12%). 5 patients (20%) developed Bortezomib induced peripheral neuropathy.Life threatening intracranial haemorrhage occurred in two patients (8%). Death occurred in 3 cases (12%),2 patients due to intracranial haemorrhage and another from cardiac arrest. In this study,S. creatinine, â2 microglobulin and bony lesion variables showed significant association with treatment response. Conclusion: Bortezomib plus dexamethasone is a highly effective and safe regimen for previously untreated multiple myeloma patients. This novel therapy in myeloma represent a new trearment paradigm targeting both tumor and microenvironment which has markedly improve overall response(OR), long progression free survival (PFS) and overall survival (OS)across in all risk groups. Moreover,it can be administered safely in the outpatient setting provided by clinicians. J Dhaka Medical College, Vol. 28, No.1, April, 2019, Page 34-41

scholarly journals Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2540-2546 ◽  
Author(s):  
E Gluckman ◽  
H Esperou-Bourdeau ◽  
A Baruchel ◽  
M Boogaerts ◽  
J Briere ◽  
...  
Keyword(s):  
Partial Response ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Bone Marrow Failure ◽  
Randomized Study ◽  
Alternative Therapy ◽  
Survival Rates ◽  
Severe Aplastic Anemia ◽  
Actuarial Survival ◽  
Significant Difference

Abstract We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3254-3254
Author(s):  
Francesco Mazziotta ◽  
Gabriele Buda ◽  
Nadia Cecconi ◽  
Giulia Cervetti ◽  
Lorenzo Iovino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
High Dose ◽  
Roc Curve Analysis ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Impact

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

A Phase II Study of PS-341 for Patients with High Risk, Newly Diagnosed Multiple Myeloma: A Trial of the Eastern Cooperative Oncology Group (E2A02).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2546-2546 ◽  
Author(s):  
Angela Dispenzieri ◽  
Emily Blood ◽  
David Vesole ◽  
Rafael Fonseca ◽  
Natalie Callander ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
High Risk ◽  
Partial Response ◽  
Progressive Disease ◽  
Response Rate ◽  
Cell Labeling ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Background: Multiple myeloma (MM) is an incurable disease with a anticipated overall survival (OS) ranging from months to decades. Modest improvements in OS have been made with high-dose chemotherapy with peripheral blood stem cell transplant (PBSCT), but to date prognostic factors have a greater impact on OS than do individual therapies. Patients with adverse risk factors such as elevated beta-2 microglobulin (B2M), plasma cell labeling index, deletions of the long arm of chromosome 13 by metaphase cytogenetics (del 13q) require innovative new treatment strategies. Bortezomib has significant activity in patients with both newly diagnosed and relapsed/refractory MM, but its specific role in patients with adverse features has not yet been defined. Methods: Patients with newly diagnosed “high-risk” myeloma (B2M ≥ 5.5., PCLI ≥ 1, or del 13q) and adequate organ and functional status were eligible. Patients were treated with bortezomib 1.3 mg/m2 day 1, 4, 8, and 11 every 21 days for 8 cycles as induction. After induction, patients were scheduled to receive bortezomib 1.3 mg/m2 every other week indefinitely. Elective peripheral stem cell mobilization (growth factor alone) was allowed after 4 cycles of bortezomib. Patients relapsing on maintenance schedule were to have the full induction schedule resumed. Responses were by the EBMT criteria but a very good partial response category was included. The primary end-point was the response rate in these high-risk patients (90% power to detect a response rate of 50% or higher). The study decision rule requires that 16 or more responses, among 39 eligible patients, are seen in order to declare this treatment effective. Results: Between March 15, 2004 and March 10, 2005, 44 patients enrolled on study. Among the 43 eligible patients, median age was 63; 51% were male. All patients had high risk disease: del 13q (6/41); plasma cell labeling index ≥1% (16/34); and B2M≥5.5 (34/43). Preliminary response data are available for 18 of the 44 cases enrolled, of which 7 had partial response, 1 had minimal response, 1 had no response, 2 had progressive disease, and 5 were unevaluable. Among those patients completing induction therapy and with response information, the median number of cycles of therapy administered is 5, range (0,8). The most common non-hematologic adverse events (AEs) of grade 3 or higher included hyponatremia (9 patients) and diarrhea (6 patients). Mild sensory peripheral neuropathy was common: grade 1, 16 patients; grade 2, 2 patients. Only 1 patient had grade 3 peripheral neuropathy. One patient died after receiving 2 doses bortezomib due to heart block and asystole. Two patients had a grade 4, 25 patients had grade 3, and 13 had grade 1 or 2 as the worst grade non-hematologic adverse event. Based on data received by August 1, 2005, 18 patients have gone off study: AEs (2); death (1); progressive disease (9); and other reasons (6). Updated results on the full study population along with FISH data for IgH translocations and deletions of 13q and 17p will be presented at the meeting. Conclusions: Preliminary results suggest that upfront bortezomib has activity in patients with high-risk MM, but further follow-up is required.

Clinical Epidemiological Study on Multiple Myeloma in China: A 18-Year Retrospective Study in a Representative Center

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2723-2723
Author(s):  
Lugui Qiu ◽  
Yafei Wang ◽  
Peijing Qi ◽  
Dehui Zou ◽  
Yaozhong Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Response Rate ◽  
Staging System ◽  
Chinese Patients ◽  
Onset Age ◽  
Successive Treatment ◽  
Western Countries ◽  
Presenting Symptoms ◽  
Number Of Patients

Abstract Aims To make up the absence of the intact epidemiological data by investigating the clinical epidemiological features of Chinese patients with multiple myeloma in a representative center. Methods: Medical records of patients with MM from January 1990 to December 2007 in our hospital were retrospectively studied, and divided into 2 groups (1990s and 2000s) to make a comparison. Results: Patients A total of 944 cases, who came from 26 Provinces, were enrolled during the past 18 years. 416 of the cases were diagnosed in 1990s, and 528 cases were enrolled after 2000. Presenting and clinical features The median onset age was 58 years with a spike of 55–65 years. There were no significant differences in the median onset age and spike period between the 2 groups, while the percentage of younger (< 40 years) was lower and elder (≥70 years) was higher in 2000s than those in 1990s (10.2% vs 5.3%, 11.3% vs 15.1%). The ratio of male to female was 2.35:1 in 2000s and 1.72:1 in 1990s.The median onset course was 5 months in 1990s and 4 months in 2000s. The main presenting symptoms were bone pain (60%) and fatigue (50%), followed by infection (20%) and bleeding (6%).534 of 688 (77.6%) previously untreated patients were in D-S stage III. The staging distribution between the two groups were no obvious difference, but patients in 2000s had lower renal insufficiency than those in 1990s (16.32% vs 33.22%). The paraprotein typed was defined in 744 cases. 47.1% were IgG type followed by IgA type (23.9%), light chain type(20.6%). IgD type was identified in 3.2%, biclonal type in 0.97%, IgM type in 0.55% and nonsecretory type in 3.87% of patients. Among the 251 patients who had convention karyotype analysis, 61.4% were normal karyotype, followed by hypodiploidy (11.95%), hyperdiploid (8.8%). Complex karyotypes were seen in 15.9% of patients, □¢13 in 8.8%, abnormality of chromosome 14 in 10.4%. 19.0% of the 100 patients with the FISH detection of 13q− (RB1 probe) was positive. Treatment and response The main treatment regimens in 1990s were MP, M2 and VAD. The response rate (≥PR) were 48.6%, with 14.9% reached ≥VGPR. There were 438 cases accepted successive treatment mainly with MPT, VAD-T/DVD-T and VD(velcade + HD-DXM)-like regimens in 2000s. The total RR were 82.0%, with 31.0% of patients reached ≥VGPR. The total response rate especially ≥VGPR was significantly improved after 2000(P<0.01). Follow-up and survival The median OS of patients in 1990s and 2000s was 30.5 and 42 months, respectively. The median OS of patients in 2000s was significant longer than those of 1990s (P<0.01) Prognostic factors The multivariate analysis of the 438 patients after 2000 indicated that β2-macroglobin, lactic dehydrogenase, 13q− had independent prognostic value for survival. The International Staging System and Durie-Salmon Staging System were effective for Chinese myeloma patients. Conclusions The number of patients admitted to hospital and the percentage of patients received successive treatment are increasing after 2000. Compared with patients in western countries, Chinese MM patients had some specific features: younger onset age, longer course before diagnosis, more invasive performance, advanced clinical stage, more unfavorable prognostic factors. The OS of patients in China was relative shorter than those reported in the western countries during the same period. The OS duration was significantly prolonged after the year 2000 with the application of thalidomide, bortezomib, and autologous haemopoietic stem cell transplantation. The main unfavorable prognostic factors of Chinese patients were similar to that of the western patients.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Factors predictive of outcome in relapsed, refractory multiple myeloma patients treated with bortezomib, melphalan, prednisone, and thalidomide (VMPT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8048-8048
Author(s):  
A. P. Palumbo ◽  
M. T. Ambrosini ◽  
G. Benevolo ◽  
N. Pescosta ◽  
V. Callea ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Response Rate ◽  
C Reactive Protein ◽  
Chromosome 13 ◽  
Refractory Multiple Myeloma ◽  
Β2 Microglobulin ◽  
Reactive Protein ◽  
Combination Methods ◽  
Line Of Therapy

8048 Background: In relapsed/refractory multiple myeloma (MM) patients, the addition of thalidomide and bortezomib to the standard oral melphalan/prednisone (VMPT) significantly increased response rate and progression-free survival (PFS) (Blood. 2006 Dec 5; [Epub ahead of print]). Baseline parameters which may predict outcome after VMPT have been investigated to identify which patient subgroups most benefit from this drug combination. Methods: Thirty patients with relapsed or refractory MM after 1 or 2 lines of treatment, were treated with six 35-days courses of bortezomib (3 dose levels: 1.0,1.3 and 1.6 mg/m2) on days 1,4,15,22, plus melphalan (6 mg/m2) and prednisone (60 mg/m2) on days 1–5 and thalidomide (50 mg) on days 1–35. Several parameters such as age, β2-microglobulin, C-reactive protein, chromosome 13 abnormalities, albumin, haemoglobin, stage, creatinine, bone marrow plasmacytosis, line of therapy and dosage of bortezomib were analyzed in association with response rate and PFS, using χ2 and Cox model. Results: At least a very good partial response was achieved in 43% of patients and at least a partial response in 67%. The 1-year PFS was 61%, and the 1- year overall survival was 84%. Subgroup analyses did not show any statistical difference between responses and either age, β2 microglobulin, C-reactive protein, chromosome 13 abnormalities, line of treatment or dosage of bortezomib. Serum albumin <3.5 mg/dL was loosely associated with a lower response rate (p=0.09). Factors predictive of shorter PFS were C-reactive protein = 6 mg/L (p=0.02) and 3rd line of therapy (p=0.009). Factors loosely associated with shorter PFS were β2-microglobulin = 3.5 mg/L (p=0.06) and creatinine = 2 mg/dL (p=0.09). No difference in PFS was observed between patients with or without chromosome 13 abnormalities. Conclusions: VMPT induced a high proportion of responses and appeared to overcome the poor prognosis of patients with chromosome 13q deletion. [Table: see text]

Standard Chemotherapy Compared With High-Dose Chemoradiotherapy for Multiple Myeloma: Final Results of Phase III US Intergroup Trial S9321

2006 ◽  
Vol 24 (6) ◽  
pp. 929-936 ◽  
Author(s):  
Bart Barlogie ◽  
Robert A. Kyle ◽  
Kenneth C. Anderson ◽  
Philip R. Greipp ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Randomized Trial ◽  
Survival Time ◽  
Standard Dose ◽  
Response Rates ◽  
Prospective Randomized Trial ◽  
Phase Iii ◽  
High Dose ◽  
Tumor Reduction

Purpose Results of a prospective randomized trial conducted by the Intergroupe Francais du Myélome (IFM 90) indicated that autologous hematopoietic cell–supported high-dose therapy (HDT) effected higher complete response rates and extended progression-free survial (PFS) and overall survival (OS) compared with standard-dose therapies (SDT) for patients with multiple myeloma (MM). Patients and Methods In 1993, three North American cooperative groups launched a prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m2 plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine, MEL, cyclophosphamide, and prednisone regimen. Responders on both arms (≥ 75%) were randomly assigned to interferon (IFN) or no maintenance treatment. Results With a median follow-up time of 76 months, no differences were observed in response rates between the two study arms (HDT, n = 261 patients; SDT, n = 255 patients). Similarly, PFS and OS durations did not differ between the HDT and SDT arms, with 7-year estimates of PFS of 17% and 16%, respectively, and OS of 37% and 42%, respectively. Of 242 patients achieving at least 75% tumor reduction, no difference was observed in PFS or OS among the 121 patients randomly assigned to IFN and the 121 patients randomly assigned to no maintenance therapy. Among 157 patients relapsing on SDT, 87 received a salvage autotransplantation; their median survival time of 30 months was only slightly better than the survival time of the remaining patients who were managed with further SDT (23 months; P = .13). Conclusion The HDT and SDT regimens used in S9321 yielded comparable response rates and PFS and OS durations. IFN maintenance therapy did not benefit patients who achieved ≥ 75% tumor reduction on either arm.

scholarly journals Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study

Blood ◽  
2012 ◽  
Vol 119 (20) ◽  
pp. 4608-4613 ◽  
Author(s):  
Suzanne Lentzsch ◽  
Amy O'Sullivan ◽  
Ryan C. Kennedy ◽  
Mohammad Abbas ◽  
Lijun Dai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Response Rate ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Dose Escalation Study ◽  
Refractory Multiple Myeloma ◽  
One Year

Abstract This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.

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