High-Dose Therapy Followed by Autologous HSCT in Patients with Multiple Myeloma. Results of a Retrospective Multicenter Analysis Conducted by The Polish Myeloma Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5108-5108
Author(s):  
Wanda M. Knopinska-Posluszny ◽  
Andrzej Hellmann ◽  
Michal Taszner ◽  
Anna Dmoszynska ◽  
Wiktor Jedrzejczak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progenitor Cells ◽  
Bone Structure ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Albumin Level ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Abstract In recent years high-dose therapy with autoHSCT has become the treatment of choice for eligible patients with multiple myeloma. This disease is now one of the most common indications for autotransplantation. The aim of this study was the clinical assessment of patients who underwent autotransplantation of progenitor cells and an analysis of the results of conducted treatment. The Polish Myeloma Group collected results of auto HSCT from 12 transplantology centres in Poland conducted between 1995 and 2006. We analyzed retrospectively the prognostic influence of pre-transplant characteristics on response and survival in 498 patients. Virtually all the patients received peripheral blood stem cell support after conditioning with melphalan (95%). We evaluated the influence of age, type of myeloma, Durie-Salmon stage, presence of renal impairment, plasma cell infiltration, albumin and b2 microglobulin level at diagnosis, status prior to and post HSCT, time from diagnosis to HSCT on overall survival (OS) and progression-free survival (PFS) to define patients with better prognosis. 232 females and 266 males underwent auto HSCT, and these included 297 (59,6%) with IgG, 97 (19,5%) with IgA, 31 (6%) with B-J, 22 (4,4%) with non-secretory myeloma. Bone structure changes were ascertained in 355 patients (71%). Bone marrow involvement higher than 20% was found in 282 patients (56,6%) at diagnosis. A decreased level of albumin (<35g/l) was determined in 168 patients (33,7%), and b2microglobuline level above 3,5 mg/l in 124 patients (24,9%). Transplantation of progenitor cells was conducted as consolidation of first line treatment following chemotherapy according to VAD in the majority of patients (74,7%). This number increased to 246 (49,4%) following transplantation. Double transplantation was conducted in 132 patients (26,5%). Median OS and PFS obtained were 3272 (1391–4232) and 1158 (102–3767) days respectively. CR achieved before transplantation, normal renal function, albumin level above 35g/l, b2 mikroglobulin below 3,5mg/l and DS stage I, were associated with a longer OS and PFS (p<0,05). This retrospective, multicenter study confirms the efficacy and safety of autoHSCT in multiple myeloma patients. Additional confirmation is given of the increased rate of CR, and the significantly prolonged survival observed in complete responders. Taking the above into account the employment of new drugs, such as thalidomide or bortezomib, which allow the achievement of a higher percentage of remissions should in the future bring about an improvement of the efficacy of transplantation in multiple myeloma.

Maintenance Therapy for Myeloma: How Much, How Long, and at What Cost?

2012 ◽  
pp. 515-522 ◽  
Author(s):  
Michel Attal ◽  
Murielle Roussel
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Second Primary ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Overview: Maintenance therapy in multiple myeloma has been under investigation for more than 3 decades and has been without evidence of clear advantage in terms of progression-free survival (PFS) until the mid-2000s. Neither conventional chemotherapy, prednisone, nor interferon-based maintenance regimens offered any benefit after conventional or high-dose therapy. Thalidomide was the first drug, mainly given as maintenance after high dose therapy, to demonstrate clinical benefits in terms of PFS and, in some studies, of overall survival (OS). The role of other novel agents such as lenalidomide and bortezomib as maintenance therapy is emerging. Lenalidomide has been shown to reduce the risk of relapse with longer follow-up needed to see if this will translate into a survival benefit. At present, a number of key questions remain unanswered. What are the optimal dose and duration of those treatments? Is the risk of toxicity and second primary malignancies acceptable? Will the disease be more aggressive at time of relapse? Is the clinical benefit predicted by initial prognostic factors and response to previous therapy? Does maintenance therapy work by further eradication of minimal residual disease or by immunological control of the malignant clone? Ongoing randomized trials are evaluating lenalidomide and bortezomib, both in the transplant and nontransplant settings, to better define the role of these drugs as maintenance in multiple myeloma.

Induction Therapy in Multiple Myeloma

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 306-312 ◽  
Author(s):  
Jean-Luc Harousseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Hematologic Malignancies ◽  
Tumor Burden ◽  
Prolonged Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
High Dose Melphalan

Abstract In most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). In multiple myeloma this has been possible only with the introduction of high-dose therapy plus autologous stem-cell transplantation (ASCT). In the context of ASCT there is a statistical relationship between CR or very good partial remission (VGPR) achievement and progression-free survival or overall survival. High-dose therapy consists of 3 to 6 courses of a dexamethasone alone or combined with vincristine-adriamycin (VAD) to reduce the tumor burden and the plasma cell infiltration followed by 1 or 2 courses of high-dose melphalan plus ASCT. This treatment induces 20% to 40% CR and 40% to 55% CR/VGPR. The introduction of novel agents in the induction treatment is changing this scenario. The combinations of dexamethasone with thalidomide, bortezomib or lenalidomide increase the CR/VGPR rates compared to dexamethasone or VAD. Triple combinations are currently being evaluated, but preliminary results with not more than 3 or 4 cycles show post-ASCT CR/VGPR rates of 60% to 75% In elderly patients who are not candidates for ASCT, combinations of melphalan-prednisone with a novel agent (thalidomide, bortezomib or lenalidomide) yield CR/VGPR rates that are quite comparable to those achieved in younger patients with ASCT. Prolonged treatment with the combination of lenalidomide plus dexamethasone can be administered safely and appears to induce very high (up to 70%) CR/VGPR rates as well.

scholarly journals Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma

Haematologica ◽  
2007 ◽  
Vol 92 (10) ◽  
pp. 1399-1406 ◽  
Author(s):  
H. J.K. van de Velde ◽  
X. Liu ◽  
G. Chen ◽  
A. Cakana ◽  
W. Deraedt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
High Dose Therapy ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Survival ◽  
Dose Therapy

scholarly journals Efficacy of repeat myeloablative chemotherapy with autologous stem-cell support in multiple myeloma

2012 ◽  
Vol 3 (2) ◽  
pp. 81-88
Author(s):  
Helge Menzel ◽  
Katarzyna Hinmüller ◽  
Hans-Jochem Kolb ◽  
Tibor Schuster ◽  
Alexander Hoellein ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
Stem Cell Support ◽  
Dose Therapy ◽  
Cell Support

Objective: Induction high-dose chemotherapy followed by myeloablative melphalan (HD-Mel) treatment and autologous hematopoietic stem-cell support (autoSCT) is a standard treatment for multiple myeloma (MM) either upfront or in relapse after conventional treatment. We performed a retrospective analysis of consecutive patients undergoing a late repeat HD-Mel/autoSCT treatment for MM. Methods: Data from 24 consecutive patients with MM who underwent a myeloablative treatment with HD-Mel late after completion of upfront first high-dose therapy were assessed for toxicity, response, progression-free survival (PFS) and time to next treatment (TTNT). These data were correlated with the results obtained after the initial high dose therapy and autoSCT. Results: A total of 23 patients were treated with novel drugs (lenalidomide, thalidomide, bortezomib) after relapse to initial autoSCT. The median overall survival (OS) of all patients was 90 months. 19 patients (79%) achieved a very good partial remission (VGPR) or complete remission (CR) after initial autoSCT, compared with 42% after late autoSCT. PFS and TTNT were 19 and 24 months after initial compared with 13 and 21 months after late autoSCT. Univariate analysis identified initial response duration and the achievement of a CR/VGPR after the initial transplantation to be associated with prolonged response after repeat autoSCT. Conclusions: Our data indicate that late high-dose treatment followed by autoSCT is safe and effective after upfront intensive treatment, can bridge to allogeneic SCT, and encourage collection of an additional graft.

Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2345-2350 ◽  
Author(s):  
Ranjit K. Dasgupta ◽  
Peter J. Adamson ◽  
Faith E. Davies ◽  
Sara Rollinson ◽  
Philippa L. Roddam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Standard Dose ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Glutathione S Transferase ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
The Impact

Abstract Glutathione S-transferase P1 (GSTP1) is a phase 2 drug metabolism enzyme involved in the metabolism and detoxification of a range of chemotherapeutic agents. A single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower thermal stability and altered catalytic activity. We hypothesized that patients with the less stable variant have a decreased ability to detoxify chemotherapeutic substrates, including melphalan, and have an altered outcome following treatment for multiple myeloma. We have assessed the impact of GSTP1 codon 105 polymorphisms in 222 patients entered into the Medical Research Council (MRC) myeloma VII trial (comparing standard-dose chemotherapy with high-dose therapy). In the standard-dose arm, patients with the variant allele (105Val) had an improved progression-free survival (PFS) (adjusted hazard ratios for PFS were 0.55 for heterozygotes and 0.52 for 105Val homozygotes, compared with 105Ile homozygotes; P for trend = .04); this was supported by a trend to improved overall survival, greater likelihood of entering plateau and shorter time to reach plateau in patients with the 105Val allele. No difference in outcome by genotype was found for patients treated with high-dose therapy. However, the progression-free survival advantage of the high-dose arm was seen only in patients homozygous for 105Ile (P = .008). (Blood. 2003;102:2345-2350)

scholarly journals Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy

2004 ◽  
Vol 34 (3) ◽  
pp. 235-239 ◽  
Author(s):  
S Kumar ◽  
M A Gertz ◽  
A Dispenzieri ◽  
M Q Lacy ◽  
L A Wellik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Value ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Total Therapy With Tandem Transplants for Newly Diagnosed Multiple Myeloma

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 55-65 ◽  
Author(s):  
B. Barlogie ◽  
S. Jagannath ◽  
K.R. Desikan ◽  
S. Mattox ◽  
D. Vesole ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Remission Induction ◽  
Comprehensive Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Total Therapy ◽  
Macrophage Colony ◽  
Intent To Treat

Abstract Between August 1990 and August 1995, 231 patients (median age 51, 53% Durie-Salmon stage III, median serum β-2-microglobulin 3.1 g/L, median C-reactive protein 4 g/L) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy (“Total Therapy”). Remission induction utilized non–cross-resistant regimens (vincristine-doxorubicin-dexamethasone [VAD], high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection, and etoposide-dexamethasone-cytarabine-cisplatin). The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete (CR) or partial (PR) remission was maintained after the first transplant; in case of less than PR, total body irradiation or cyclophosphamide was added. Interferon--2b maintenance was used after the second autotransplant. Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle. Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84% and 71% (the majority within 8 and 15 months, respectively). Eight patients (3%) died of toxicity during induction, and 2 (1%) and 6 (4%) during the two transplants. True CR and at least a PR (PR plus CR) were obtained in 5% (34%) after VAD, 15% (65%) at the end of induction, and 26% (75%) after the first and 41% (83%) after the second transplants (intent-to-treat). Median overall (OS) and event-free (EFS) survival durations were 68 and 43 months, respectively. Actuarial 5-year OS and EFS rates were 58% and 42%, respectively. The median time to disease progression or relapse was 52 months. Among the 94 patients achieving CR, the median CR duration was 50 months. On multivariate analysis, superior EFS and OS were observed in the absence of unfavorable karyotypes (11q breakpoint abnormalities, -13 or 13-q) and with low β-2-microglobulin at diagnosis. CR duration was significantly longer with early onset of CR and favorable karyotypes. Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly, independent of cytogenetics and β-2-microglobulin. Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients, using multi-regimen induction and tandem transplantation followed by interferon maintenance. As a result, the proportion of patients attaining CR increased progressively with continuing therapy. This observation is particularly important because CR is a sine qua non for long-term disease control and, eventually, cure.

Global Approaches in Myeloma: Critical Trials That May Change Practice

2018 ◽  
pp. 656-661 ◽  
Author(s):  
Philippe Moreau ◽  
Cyrille Touzeau
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Therapeutic Strategies ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
The Past ◽  
Induced Changes ◽  
The Impact ◽  
Specific Section

The treatment of multiple myeloma (MM) has changed dramatically in the past decade with the introduction of new drugs into therapeutic strategies both in the frontline and relapse settings. With the availability of at least six different classes of agents that can be combined in doublet, triplet, or even quadruplet regimens and used together with high-dose therapy and autologous stem cell transplantation, the choice of the optimal strategy at diagnosis and at relapse represents a challenge for physicians. Also problematic is the lack of trials addressing questions, such as sequencing or the duration of maintenance. This review will focus on the results of recent clinical trials both in the frontline and relapse settings that have induced changes in clinical practice and will discuss the impact of important ongoing trials. A specific section will discuss therapeutic strategies when new drugs are not available.

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