scholarly journals Zdravljenje diseminiranega plazmocitoma na Kliničnem oddelku za hematologijo UKC Ljubljana z avtologno presaditvijo krvotvornih matičnih celic v letih 2014 in 2015.

2016 ◽  
Vol 85 (9) ◽  
Author(s):  
Samo Zver ◽  
Enver Melkić ◽  
Tanja Radevska
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Induction Therapy ◽  
Progressive Disease ◽  
Induction Treatment ◽  
Hematopoietic Stem ◽  
Treatment Mortality ◽  
Good Partial Response ◽  
Autologous Hsct ◽  
Overall Mortality

Introduction. In the period from 01.01.2014 to 31.12.2015 at Clinical Department of Hematology, University Medical Centre Ljubljana, we treated 73 multiple myeloma patients with first autologous  hematopoietic stem cell transplantation (HSCT).Methods and results. Age of patients ranged from 27 to 72 years with the median age of 60 years. Induction treatment at the time of diagnosis consisted of: VD (bortezomib, dexamethasone) 60/73 patients (82%), VCD (bortezomib, cyclophosphamide, dexamethasone)  10/73  patients (14%) and VTD (bortezomib, thalidomide, dexamethasone) 3/73 (5%)  patients. As part of induction therapy, patients received from 1 to 9 cycles of treatment. Response to induction therapy prior to HSC(hematopoietic stem cells) collection was as follows: CR(complete remission )7/73(10%), VGPR (very good partial response) 28/73(38%), PR (partial response) 23/ 73(32%), SD (stable disease) 11/73(15%) andPD (progressive disease) 4/73(5%) patients. Response to induction therapy immediately prior to autologous HSCT: CR9/73 (12%), VGPR32/73 (44%), PR17/73(23%), SD 8/73(11%) and PD6/73(8%) patients. Response to induction therapy and the first autologous HSCT at D+100 after HSCT: CR9/67 (13%), VGPR 34/67 (51%), PR 12/67 (18%), SD 3/67 (4 %) and PD 7/67 (10%) patients (in 6 patients data are missing, because they are not mature yet).  With single HSCT 63 patients were treated, while 10 patients received double or second HSCT. The overall mortality of patients treated during the  period from 01.01.2014 to 31.12. 2015 was 6/73 or 8.2%.Conclusions. The treatment of multiple myeloma with autologous HSCT remains the cornerstone of efficiency,as demonstrated by the increasing share of the most desired responses to treatment, ie. CR and VGPR. The treatment mortality rate was within expectation limits.

GMMG MM5 Trial In Newly Diagnosed Multiple Myeloma To Evaluate PAd Vs VCD Induction Prior To High Dose Treatment Followed By Lenalidomide Consolidation and Maintenance – Final Analysis On Induction Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3369-3369 ◽  
Author(s):  
Hartmut Goldschmidt ◽  
Jan Duerig ◽  
Uta Bertsch ◽  
Christina Kunz ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
Partial Response ◽  
Induction Therapy ◽  
Research Funding ◽  
Treatment Strategies ◽  
Response Rates ◽  
Complete Response ◽  
Disease Stage ◽  
Induction Treatment ◽  
High Dose ◽  
Good Partial Response

Abstract Background The MM5 phase III trial of the German-Speaking Myeloma Multicenter Group (GMMG) was designed to address two independent primary objectives: 1.) demonstration of non-inferiority of VCD (bortezomib, cyclophosphamide, dexamethasone) induction compared to PAd (bortezomib, adriamycin, dexamethasone) induction therapy with respect to response rate (very good partial response or better). 2.) determination of the best of four treatment strategies with respect to progression-free survival (PFS). The four treatment strategies were defined by PAd vs. VCD induction treatment, high dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) as well as consolidation and maintenance treatment with lenalidomide for 2 years vs. lenalidomide until complete response (CR). Methods 504 patients were included in the trial between July 2010 and October 2012. A non-inferiority analysis of VCD compared to PAd with respect to response rates after induction treatment with a non-inferiority margin of 10% for the difference in response rates (VGPR and better; first primary endpoint) and a safety analysis were performed. During the induction phase the patients were treated with 3 cycles of PAd or VCD. PAd was dosed as bortezomib 1.3 mg/m2, days 1, 4, 8, 11, doxorubicin 9 mg/m2, days 1-4, dexamethasone 20 mg, days 1-4, 9-12, 17-20 (repeated every 28 days). VCD consisted of bortezomib 1.3 mg/m2, days 1, 4, 8, 11, cyclophosphamide 900 mg/m2 day 1, dexamethasone 40 mg, days 1-2, 4-5, 8-9, 11-12 (repeated every 21 days). The route of administration for bortezomib was changed from intravenously to subcutaneously in all study arms by a protocol amendment in February 2012 after inclusion of 314 patients. The non-inferiority analysis was based on intention-to-treat (ITT) population (502 evaluable patients) and per-protocol (PP) population (473 evaluable patients). Responses were assessed according to the response criteria of the International Myeloma Working Group (IMWG). Results In the ITT population, patients treated with PAd or VCD were equally distributed for ISS and Durie-Salmon disease stage, LDH, kidney function and the cytogenetic abnormalities translocation t(4;14), deletion 17p13 and gain 1q21. In the PAd group, the median age of the patients was higher (59.4 vs. 58.7, p=0.04). 229 of 251 patients (91.2%) in the PAd group and 241 of 251 patients (96.0%) in the VCD group completed induction treatment. Observed response rates (PAd vs. VCD) were 4.4% vs 8.4% for complete response, 34.3% vs. 37.0% for ≥ very good partial response and 72.1% vs. 78.1% for ≥ partial response. Non-inferiority of VCD compared to PAd was shown (two-sided p=0.0026). Similar results were obtained in the PP analysis. The proportion of patients with any adverse event (AEs) was comparable in PAd vs. VCD (61.3% vs. 64.0%, p=0.58), but more serious adverse events (SAEs) were observed during PAd induction (32.7% vs. 24.0%, p=0.037). VCD led to a significantly higher proportion of leukopenia and neutropenia CTCAE grade 3 and 4 (PAd: 11.3% vs. VCD: 35.2%; p<0.001). There was no significant difference in the number of infections (≥ CTCAE grade 2) during PAd induction compared to VCD induction (24.6% vs. 22.4%; p=0.60). Interestingly, compared to the infection rate (≥ CTCAE grade 2) of 49% during PAD (dexamethasone 40 mg days 1-4, 9-12, 17-20) in the HOVON65/GMMG-HD4-trial, a reduction in MM5 during induction was observed. In the PAd arm more deaths were observed compared to the VCD arm (6 vs. 1). Conclusion PAd and VCD are well tolerated with more than 90% of the patients receiving all three planned induction cycles. Non-inferiority of VCD compared to PAd was shown in ITT and PP analysis. In conclusion, VCD was found to be a valid alternative to PAd with comparable efficacy and a favourable toxicity profile. Disclosures: Goldschmidt: Celgene: Consultancy, Honoraria, Research Funding; Chugai: Research Funding; Janssen Cilag: Consultancy, Honoraria, Research Funding. Duerig:Janssen Cilag: Honoraria; Celgene: Honoraria. Schmidt-Wolf:Janssen: Honoraria; Novartis: Honoraria. Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Scheid:Janssen Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Salwender:Janssen Cilag: Honoraria; Celgene: Honoraria.

The Dream of a Cure in Multiple Myeloma: A 15-Year Single Center Retrospective Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5503-5503
Author(s):  
Stefano Pulini ◽  
Annalisa Natale ◽  
Anna Maria Morelli ◽  
Antonio Spadano ◽  
Stefano Angelini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Study ◽  
Partial Response ◽  
Induction Therapy ◽  
Progressive Disease ◽  
Diagnostic Tools ◽  
Cell Transplant ◽  
The Past ◽  
Line Therapy

Abstract Multiple Myeloma (MM) is still considered an incurable disease despite a substantial global outcome improvement observed during the past decade. Despite better understanding of biological pathways, availability of sophisticated diagnostic tools and increasing number of therapeutic options almost all patients experience disease relapse. The aim of our retrospective study was to analyze global outcome in newly diagnosed MM patients eligible for high dose chemotherapy and autologous stem cell transplant (ASCT) treated in our Institution in the last 15 years. We evaluated 177 MM patients transplanted in our Institution from November 1999 to February 2015. Median age at start therapy was 58 years (range 36-71) and median follow up time (from start therapy to last follow up) was 52 months (range 7-185). Patients received different induction therapies before transplant reflecting the availability of new drugs and consequently more therapeutic choices. 65 patients received conventional chemotherapy-based induction (VAD 27, 15%, Total Therapy 2-like 37, 22%, EDAP 1 patient); 15 patients thalidomide-based (TD, 8%); 88 patients bortezomib-based (VTD 74, 43%; VCD 8, 5%; PAD 3, 1%; VD 3, 1%) and 9 patients lenalidomide-based (RD, 5%). After induction regimen 23 patients (13%) received additional therapy before transplant: 14 for Progressive Disease (PD), 9 were considered in suboptimal/unsatisfactory response (5 in Partial Response, PR and 4 in Stable Disease, SD). 71 patients received a single ASCT, 106 patients double ASCT; 11 tandem autologous and allogeneic SCT. All patients had a PR/VGPR/CR after ASCT. Treatment related mortality was 1% (3 patients: 2 of them after Allogenic ASCT, 1 for acute Graft versus Host Disease, 1 for Veno Occlusive Disease). After first line therapy 7 patients died: 3 for progressive disease, 4 for other causes (2 myocardial infarction, 1 intestinal ischemia and 1 breast cancer). 90 patients (51%) experienced MM relapse (median time from ASCT 24 months) and were treated according to different chemotherapy schedules. At last follow-up 115 patients were alive (65%), 61 of them in Complete Response, 31 in Very Good Partial Response, 8 in Partial Response, 4 in SD, 11 in PD. Median global overall survival (OS) was 109 months, median global Progression Free Survival1 (PFS1) 51 months and median global PFS2 (time from start therapy to second disease progression or death from any cause) 80 months. According to different induction therapy (chemotherapy vs bortezomib vs thalidomide vs lenalidomide-based) median OS was 117 months vs not reached (more than 96) vs 68 vs not reached (more than 60); median PFS1 was 47 months vs 60 vs 35 vs not reached (more than 60); median PFS2 was 76 months vs 92 vs 57 vs not reached (more than 60), respectively. As reported in literature the improvement of biological, diagnostic and clinical knowledge and the availability of new therapeutic tools translates in improved outcome in MM patients treated in our Center. The introduction of the proteasome inhibitor bortezomib in the induction therapy gave the best results in terms of OS, control of the disease (PFS) and response to second line therapy after relapse (PFS2). Considering the remarkable progress done in the past decade the dream of a cure is a challenge for the future. Disclosures No relevant conflicts of interest to declare.

scholarly journals Autologous haematopoietic stem cell transplantation in patients with multiple myeloma complicated by dialysis-dependent renal failure

2020 ◽  
Vol 92 (7) ◽  
pp. 70-76
Author(s):  
M. V. Firsova ◽  
L. P. Mendeleeva ◽  
M. V. Solovev ◽  
I. G. Rekhtina ◽  
O. S. Pokrovskaya ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Complete Response ◽  
Haematopoietic Stem Cell ◽  
Renal Response ◽  
Good Partial Response

Aim.To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure. Materials and methods.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed. Results.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%. Conclusion.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.

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.

Safety and Efficacy of Bortezomib (VELCADE™) in 104 Patients with Relapsed and/or Refractory Multiple Myeloma Who Have Received at Least Two Previous Lines of Therapy: Impact of Cytogenetics on Response from a Canadian Cohort.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5118-5118
Author(s):  
Joseph R. Mikhael ◽  
Donna E. Reece ◽  
Andrew Belch ◽  
Nizar J. Bahlis ◽  
Deepa Sharma
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
M Protein ◽  
Cytogenetic Abnormalities ◽  
Refractory Multiple Myeloma ◽  
The Impact

Abstract Background: Bortezomib (VELCADE™) is a reversible proteasome inhibitor that has been shown to be safe and efficacious in patients (pts) with relapsed and/or refractory multiple myeloma (MM) using a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 of a 21-day cycle. Certain cytogenetic abnormalities are associated with poor prognosis in MM, including deletion 13, t(4;14) and the p53 deletion.(Stewart et al, JCO2005; 23(26):6339–44). Bortezomib has demonstrated the ability to overcome the poor prognosis associated with deletion 13 (Jagannath, JCO2005; 23(16S) 6501). The impact of bortezomib on a broader range of cytogenetic abnormalities, such as t(4;14) has yet to be determined. Methods: In this multicentre, open-label, non-randomized, phase 3b study, pts with MM across 13 centres in Canada, who had received at least 2 previous lines of therapy and who were refractory to or had relapsed after their last therapy were enrolled. Pts received up to eight 3-week cycles of bortezomib on days 1, 4, 8 & 11. Dexamethasone 20 mg PO was administered on each day of and day after bortezomib administration if the pts either experienced progressive disease after receiving at least 2 treatment cycles of bortezomib or had no change in disease status from baseline after receiving at least 4 treatment cycles of bortezomib. Results: 104 pts were enrolled; the mean age in this cohort was 60.7 years, and 65 (62.5%) were male. Approximately 30% of pts had a Karnofsky performance status of 70 or less at baseline. 71 pts (68.3%) had received prior thalidomide therapy, 32 (30.8%) had received a prior autotransplant and 4 (3.8%) had received prior bortezomib treatment. 74 (71.2%) received 3 or more lines of prior MM therapy. During the study, mean number of bortezomib cycles completed was 4.6 (range, 0–11 cycles), and the number of pts that completed 8 cycles of therapy was 36 (34.6%). 15.2% of pts received dexamethasone at cycle 3 and 19.2% at cycle 5. Cytogenetic analysis was performed on approximately half of the pts. Response data for cycle 5 is currently available for 69/99 (69.7%) of evaluable pts (see Table 1). Overall, 76.9% of the pts experienced Grade 3 & 4 adverse events. Safety profile observed is similar to past trial results with bortezomib. Conclusion: In this large Canadian cohort of extensively pre-treated patients with mulitple myeloma, bortezomib demonstrated good response, consistent with previous studies. Analysis correlating cytogenetic profile and response rate is ongoing and will be available at the time of conference. In addition, a detailed safety analysis and impact of prior treatment on response will be analyzed and made available at the time of conference. Table 1. Response to Bortezomib Category of Response* No. of Patients (%) *Modified SWOG: CR 100% M-protein reduction; R 75–99%; PR 50–74%; MR 25–49%; SD<25%, PD increasing M-protein Any Response (CR + VGPR + PR + MR) 47 (68.1) ---Complete Response (CR) + Very Good Partial Response (VGPR) ---22 (31.9) ---Partial Response (PR) + Minimal Response (MR) ---25 (36.2) Stable Disease 10 (14.5) Progressive Disease 12 (17.4)

Hypocalcemia during Autologous Stem Cell Transplant with Concurrent Biphosphonate Use in Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4335-4335
Author(s):  
Kitsada Wudhikarn ◽  
Gregory M. Vercellotti ◽  
Mukta Arora
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Serum Calcium ◽  
Plasma Cells ◽  
Remission Rate ◽  
Calcium Supplementation ◽  
Normal Serum ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Autologous Hsct

Abstract Autologous hematopoietic stem cell transplantation (HSCT) is one of the treatment options which has been shown to enhance remission rate and survival in patients with multiple myeloma. Biphosphonates are used in conjunction with standard therapy and can ameliorate and prevent bony complications, i.e. bone pain, hypercalcemia or fracture, via direct inhibition of osteoclasts and possible anti-tumor effects on malignant plasma cells. With more frequent use of biphosphonates, there are increasing reports of noticeable adverse effects such as osteonecrosis of the mandible, renal failure and hypocalcemia. In this study we report three patients with multiple myeloma who received autologous HSCT accompanied with monthly administration of bisphosphonates and developed significant hypocalcemia post HSCT. All three patients had normal serum calcium levels at diagnosis and prior to transplant. The maximum drop in serum calcium was noted four to ten days post HSCT, and corrected by five to 13 days post HSCT. All three patients received biphosphonates eight to 20 days prior to the episode of hypocalcemia. All patients noted resolution of hypocalcemia with oral and intravenous calcium supplementation over three to ten days. Two patients required ongoing oral calcium supplementation for approximately one month after resolution of hypocalcemia. Multiple potential mechanisms can be postulated for the hypocalcemia in these patients undergoing HSCT such as chronic nutritional deficiency, GI losses, renal losses, vitamin D deficiency in addition to bisphosphonate use. Potentially melphalan, IV fluids, and furosemide may also play roles. Osteoclasts, bone marrow stromal cells and myeloma cells all can modulate calcium levels directly or indirectly through cytokine production. Future laboratory and clinical studies will focus on biochemical marker of complication and attention is needed while using bisphosphonates during autologous HSCT in myeloma patients.

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.

First Asia-Pacific Co-Operative Multicenter Multiple Myeloma Clinical Trial: Preliminary Results of the “dtZ”/“DAZZLE” Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4940-4940
Author(s):  
Gerrard Teoh ◽  
Kihyun Kim ◽  
Alok Srivastava ◽  
Vasant Pai ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Osteonecrosis Of The Jaw ◽  
High Rate ◽  
Asia Pacific ◽  
Hematopoietic Stem ◽  
Asian Patients ◽  
Tract Infections

Abstract Abstract 4940 Introduction Many physicians have anecdotally reported that Asian patients with multiple myeloma (MM) are frequently unable to tolerate full doses of dexamethasone (Dex) and/or thalidomide (Thal). Unfortunately, co-operative clinical studies from the Asia-Pacific countries are presently lacking and the effective dose of the Dex/Thal combination in Asians is unknown. Since higher doses of zoledronic acid (Zol) have been shown to exert an anti-MM effect in pre-clinical models of MM, we investigated whether higher frequency dosing of Zol combined with lower doses of Dex/Thal could be an effective and better tolerated regimen in Asian patients. Moreover, since attainment of very good partial response (VGPR), near complete response (nCR) or complete response (CR) prior to autologous hematopoietic stem cell transplantation (AHSCT) correlates with good outcome in MM, we wanted to determine if this lower-dose Dex/Thal with higher-frequency dosing Zol regimen could be a good preparative regimen in transplant-eligible patients. Patients and Methods In this international co-operative multicenter phase II non-randomized single arm study in previously untreated patients with MM (n=44), all patients received up to 6 cycles of three-weekly Dex/Thal/Zol (or “dtZ”). Doses of Dex ranged from 20 mg weekly to 20 mg four times a week; and doses of Thal ranged from 50 mg weekly to 100 mg every night. Zol 4 mg was given three-weekly. Response was graded using Blade's criteria. Results The study population included 67.3% Oriental (Korean and Chinese), 30.8% Indian and 1.9% Malay patients. 15.4% of patients were ISS stage I, 61.5% stage II and 23.1% stage III prior to treatment. 39 (88.6%) patients demonstrated at least a partial response (PR); and 23 (52.3%) of patients achieved VGPR (18.2%), near nCR (15.9%) or CR (18.2%). The fastest time to VGPR/nCR/CR was 1 cycle. Most patients tolerated treatment very well and were managed in the outpatient clinic. Sepsis was the most frequently reported grade 3 or 4 toxicity – 8 (18.2%) patients developed bronchopneumonia, and 3 (6.8%) gastrointestinal or urinary tract infections. 1 (2.3%) patient was suspected of having pulmonary embolism. There were 4 (9.1%) deaths – 3 from severe sepsis and 1 from an unknown cause. Importantly, there were no reports of peripheral neuropathy, osteonecrosis of the jaw (ONJ) or end stage renal failure. In fact, there was an overall 2.4% improvement in the median creatinine clearance time (CCT). Finally, the percentage of CD34 stem cells was not adversely affected by treatment with dtZ. Conclusions The dtZ regimen appears to be an effective and well-tolerated treatment regimen for Asian patients with newly-diagnosed MM. The high rate of VGPR/nCR/CR will greatly facilitate AHSCT in transplant-eligible patients. Judicious use of low-dose Thal has abrogated the numerous side-effects associated with Thal and greatly improved patient tolerance. Even though Zol is administered at a higher frequency, it is not associated with worsening of renal function or ONJ. Infections are the most frequent and worrisome complications of treatment. These are likely to be related to the dose of Dex. Accordingly, it is probably wise to further lower the dose of Dex in future studies. (This study is registered with NIH PRS # 00263484.) Disclosures No relevant conflicts of interest to declare.

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