The impact of race on outcome of autologous transplantation in patients with multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17029-17029
Author(s):  
P. S. Verma ◽  
R. S. Howard ◽  
B. M. Weiss
Keyword(s):  
Multiple Myeloma ◽  
Racial Differences ◽  
Hematologic Malignancy ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Response To Therapy ◽  
Rank Test ◽  
High Dose ◽  
Skeletal Involvement ◽  
The Impact

17029 Background: Multiple myeloma (MM) is the most common hematologic malignancy in African-Americans (AA), with historically double the mortality of Caucasians (C). Monoclonal gammopathy of undetermined significance (MGUS) is also three times more frequent in AA than C. There has been limited data exploring racial differences in survival during the era of high dose chemotherapy with autologous stem cell transplantation (ASCT). Methods: We retrospectively analyzed the records of all C (n=55) and AA (n=36) MM patients who underwent ASCT over 10 years. Presenting demographic, clinical features and response to therapy by the Bladé criteria were obtained from medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method, and compared using the log-rank test. Results: The median age at diagnosis for AA was 52 years (30–75 years), compared to C at 56 years (39–79 years), p=0.006. There was no statistical difference in presenting ISS stage (AA: I- 50%, II- 28.1%, III- 21.9%; C: I- 51.2%, II- 20.9%, III- 27.9%), or values for presenting hemoglobin, calcium, and creatinine. There was a trend for increased skeletal involvement at diagnosis in the C group (82% vs. 69%, p=0.08). AA presented with an increased CRP (1.2 mg/dl vs. 0.25mg/dl, p=0.05). The most commonly used induction and conditioning regimen was VAD (78% AA vs. 70% C), and Mel 200 (72% AA vs. 65% C), respectively. Response to induction: CR: AA- 6%, C- 5%, p=1.00; PR: AA- 64%, C- 56%, p=0.519. Response to ASCT: CR: AA- 17%, C- 26%, p=0.438; PR: AA- 56%, C- 46%, p=0.519. At a median follow-up of 46.7 months, PFS was 60.5 months and 43.7 months (p=0.490), for AA and C, respectively; OS was 95.2 months and 68.5 months (p=0.421), for AA and C, respectively. Conclusion: In this series, AA with MM present at a younger age, with an increased CRP and a trend for less skeletal involvement than C at diagnosis. Despite a trend for less CR rates in AA, there was a trend for increased PFS and OS compared to C. This suggests there are biologic differences in MM between the races that may result in different therapeutic outcomes. One possible explanation would be the known higher frequency of MGUS in AA resulting in a reversion to a stable, indolent MGUS-like state after ASCT. These findings should be confirmed in larger studies. No significant financial relationships to disclose.

scholarly journals Relative Abundance Analysis of the Oral and Gastrointestinal Microbiome during Autologous Transplantation for Multiple Myeloma: Results of a Prospective Pilot Study and Association with Transplant Outcomes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5754-5754
Author(s):  
Najla H El Jurdi ◽  
Ali Filali ◽  
Iman Salem ◽  
Mauricio Retuerto ◽  
Nina Dambrosio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Relative Abundance ◽  
Bacterial Community Composition ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Small Sample ◽  
High Dose ◽  
Gastrointestinal Microbiome ◽  
Fecal Microbiome ◽  
Significant Difference

Abstract Background The human microbiome has been associated with allogeneic hematopoietic cell transplantation (HCT) outcomes. To date, there are no studies describing the longitudinal changes in the oral or gastrointestinal microbiome in the setting of autologous HCT. We conducted a prospective study to determine the longitudinal microbial profile in patients undergoing HCT for multiple myeloma (MM), and whether changes in microbial abundance correlate with HCT outcomes and/or toxicities. Methods Samples were collected from 15 MM patients on admission (baseline, T-2), during marrow aplasia (T+7) and after engraftment (T+30) (Table 1- summarizes baseline characteristics). We evaluated the bacterial and fungal microbiome of 15 patients using Ion-Torrent PGM workflow. The amplicons generated from the 16s rRNA and the ITS genes were sequenced for bacterial and fungal identification, respectively. Sequencing reads were clustered into operational taxonomic units (OTUs, 3% distance) and taxonomically classified via Qiime bioinformatics pipeline. Statistical analysis was performed using the statistical programming language R. Multivariate distance based association between communities and outcome was performed using the Adonis function as implemented in the R package vegan using Bray-curtis dissimilarities distances with and without presence/absence standardization (BrayPA). Non-parametric Spearman correlation and wilcoxon rank-sum test were used for association with continuous outcome and binary outcome respectively. Results Relative abundance was determined at the phylum and genus levels across each time point, in the oral and fecal microbiome, both bacterial and fungal. At the bacterial phylum level, the oral bacterial community composition significantly changed at T+30 compared to baseline (Bray-curtis, p=0.046) and T+7 (Bray-curtis, p=0.025). When examining the changes in the mycobiome composition, test for dissimilarity showed a significant difference in the fecal fungal genus between baseline and T+30 (BrayPA, p=0.025). No other statistically significant differences were noted. Next, we correlated the microbial community (Table 2) and individual composition with outcome and transplant related toxicity, the later will be reported here. In fecal samples, the bacterial phylum Bacteriodetes present at T+7 was associated with the development and severity of diarrhea, such that patients with higher abundance of Bacteroidetes experienced lower gastrointestinal toxicity (pAdj=0.03). Additionally, the 2 genera Blautia and Ruminococcus, both belonging to the Firmicutes phylum and Clostridium Class, when detected at T+7 were associated with a higher development and severity of vomiting after exposure to high dose melphan (pAdj=0.05 for both respectively). In oral samples, the presence of the genus Glomerella at T+7 was negatively associated with rates of neutrophil engraftment (pAdj=0.03). Conclusion and Future Directions While acknowledging the limitation inherent in the small sample size, our results show that oral and fecal microbiota undergo dynamic changes in their diversity (Abstract ID 120038), composition and relative abundance during the course of transplantation. This change is likely multifactorial owing to the conditioning regimen, antimicrobial exposure and immune dysregulation. Our data suggest the bacterial and fungal microbiota present specifically at count nadir could be important players in this population of patients. Interestingly, the relative abundance of particularly the anaerobic bacterial phyla, Bacteroidetes and Firciumtes (Blautia and Ruminococcus) during marrow aplasia, correlated with transplant related toxicities in our cohort. This could further contribute to our knowledge of the role anaerobic organisms play in HCT outcomes, in accordance to what has been described in the allogeneic HCT literature. Amifostine was used as a cytoprotectant before high dose melphalan for our patients. The effect of this organic thiophosphate on the microbiota is unclear and warrants future investigations. Further studies conducted on a larger scale and incorporating metabolomics and proteomics will help elucidate the interactions between the host and the microbiome and their effect on short term and long term transplantation outcomes as well as toxicities. Disclosures Lazarus: Pluristem Ltd.: Consultancy. Malek:Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.

Superiority of First-Line Thalidomide-Dexamethasone over Vincristine-Doxorubicin-Dexamethasone in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1489-1489 ◽  
Author(s):  
Michele Cavo ◽  
Paola Tacchetti ◽  
Elena Zamagni ◽  
Patrizia Tosi ◽  
Delia Cangini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Clinical Stage ◽  
Autologous Transplantation ◽  
Cell Mass ◽  
Response To Therapy ◽  
High Dose ◽  
Control Analysis ◽  
Primary Therapy ◽  
Matching Criteria

Abstract The aim of the present study was to compare thalidomide-dexamethasone (THAL-DEX) and vincristine-doxorubicin-dexamethasone (VAD) as primary therapy for newly diagnosed multiple myeloma (MM). For this purpose, we performed a retrospective matched case-control analysis of 200 patients who were treated with THAL-DEX (n=100) or VAD (n=100) on two consecutive studies from 1996 to 2003. Thalidomide was given orally at the daily dose of 200 mg, while VAD was administered by continuous infusion. Pulsed dexamethasone combined with thalidomide or vincristine-doxorubicin was given at the monthly dose of 40 mg/d for 4 days (1 to 4), with courses repeated on days 9 to 12 and 17 to 20 on odd cycles. By design of both studies, THAL-DEX and VAD were planned to be given for 4 months in an attempt to reduce tumor cell mass before collection of peripheral blood stem cells (PBSC) and subsequent autologous transplantation. Matching criteria were age (within 2 years), clinical stage and serum β2-microglobulin (within 1 mg/l). In addition to the above mentioned criteria, all other relevant baseline patient characteristics were comparable between the two groups. Response to therapy was evaluated using an intent-to-treat approach and stringently defined criteria (EBMT). In comparison with VAD, THAL-DEX resulted in a significantly higher ≥ partial response rate (76% versus 52%, respectively; P=0.0004) and effected more profound reduction in serum IgG (P=0.002) and IgA (P=0.01) M protein levels. Nine patients treated with THAL-DEX and 9 patients who received VAD did not proceeded to PBSC mobilization, mainly because of death while on study treatment (THAL-DEX=5 patients; VAD=6 patients) or nonfatal toxicity (THAL-DEX=3 patients; VAD=2 patients). The median number of CD34+ cells collected following high dose cyclophosphamide 7 g/m2 was 7.85 x 106/kg in the THAL-DEX group and 10.5 x 106/kg in the VAD group. Considering 4 x 106 CD 34+/kg as the minimum number of stem cells required to safely perform double autologous transplantation, adequate cell yields were obtained in 83% of patients with prior exposure to THAL-DEX and in 88% of patients treated with VAD (P=0.3). In conclusion, results of the present study (to the best of our knowledge, the first comparing THAL-DEX with VAD as initial cytoreductive therapy in preparation for autologous transplantation) extend and confirm prior observations by our group and others showing that THAL-DEX is an effective and relatively well tolerated induction regimen for previously untreated patients with MM. In comparison with VAD, THAL-DEX significantly augmented tumor cytoreduction without increasing the toxicity or interfering with subsequent collection of PBSC. Based on these data, thalidomide-dexamethasone may be considered an oral, and easy to administer, alternative to the more complex, and cumbersome to administer, combination of vincristine-doxorubicin-dexamethasone as front-line therapy for MM patients who are candidates to subsequent autologous transplantation.

Flow Cytometric Detection of Circulating Myeloma Cells Pretransplant in Patients with Multiple Myeloma: A Simple Risk Stratification System.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1164-1164
Author(s):  
David Dingli ◽  
Grzegorz S. Nowakowski ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Response To Therapy ◽  
Independent Prognostic Factor ◽  
High Dose ◽  
Rapid Progression ◽  
Myeloma Cells ◽  
The Impact

Abstract Background: The presence of circulating myeloma cells (CMC) detected by flow cytometry at the time of diagnosis of multiple myeloma is associated with a shortened response to therapy and reduced overall survival (OS). We hypothesized that the presence of CMC at the time of stem cell collection prior to high dose therapy (HDT) and autologous stem cell transplantation (ASCT) would identifies a cohort of patients with a high risk of rapid progression. Methods: The Mayo Clinic myeloma transplant database was queried for patients who were mobilized using cyclophosphamide and hematopoietic growth factors. CMC was determined using flow cytometry by gating on a population of CD38 bright and CD45 negative cells. The impact of CMC on OS and time to progression (TTP) and its role in the context of established prognostic parameters was evaluated. Results: Of 246 patients with MM undergoing ASCT, 95 had CMC. Patients with CMC had significantly higher plasma cell labeling index, adverse cytogenetics, B2-M and resistant disease. Complete response (CR) rates post transplant were 32% and 36% for patients with and without CMC (p=0.5034). OS was 33.2 and 58.6 months (p=0.0052) while TTP was 14.1 and 22 months respectively (p=0.0005). Figure Figure On multivariate analysis, CMC remained an independent prognostic factor in a model that included cytogenetics and disease status at time of transplant (p=0.0314). A prognostic system based on the presence or absence of CMC and karyotype abnormalities was developed. Patients with neither, one or both parameters had a median, OS of 55, 48 and 21.5 months respectively (p<0.0001) while TTP was 22, 15.4 and 6.5 months for the same groups (p<0.0001). Conclusion: The presence of CMC at the time of HDT and ASCT is an independent prognostic factor. The combination of CMC and cytogenetics provides a simple yet powerful scoring system that stratifies patients and guides their management.

African American Patients with Multiple Myeloma Have Prolonged Responses after Autologous Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3131-3131
Author(s):  
Santosh Saraf ◽  
Yi-Hsiang Chen ◽  
Lisa C. Dobogai ◽  
Yogen Saunthararajah ◽  
David Peace ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose ◽  
Racial Groups ◽  
Skeletal Involvement ◽  
Clinical Responses ◽  
High Dose Melphalan ◽  
The University

Abstract The incidence of multiple myeloma (MM) in African American (AA) patients is higher than in other racial groups. In this retrospective study we analyzed the outcome of 70 consecutive patients (AA n=38, non-AA n=32) with MM receiving an autologous stem cell transplantat (ASCT) at the University of Illinois at Chicago. No significant differences, including age, gender, stage of disease, Hgb and b2 microglobulin levels, skeletal involvement, plasma cell marrow infiltration, were observed between AA and non-AA patients at diagnosis. Chemotherapy prior to ASCT was also comparable in the two groups. Conditioning regimen with high dose melphalan was used in 84% AA and 72% non-AA, while the remaining patients received BCNU/melphalan. After induction chemotherapy no difference occurred in complete remission (CR) and partial remission (PR) rates in AA (9% and 42%) as compared to non-AA (13% and 33%). Two months after transplantation CR and PR rates were 31% and 25% in AA and 30% and 20% in non-AA. However, at 6 months after ASCT 25%AA vs 60% non-AA patients showed a progression of the disease (p=0.009). At a median follow-up of 26 months (range:1 to 89), 79% AA and 69% non-AA patients are alive. The estimated median Event-Free-Survival in the two groups is 21 vs 12 months (p=0.02), while the estimated median Overall Survival is 64 vs 39 months (p=0.19) (Figure 1). In conclusion, AA and non-AA patients have similar CR and PR rates after ASCT. However, AA patients seem to have more prolonged clinical responses. In a setting where equal access to modern modalities of treatment is available, race does not appear to affect responses to therapy in multiple myeloma. Figure 1 Figure 1.

Cyclophosphamide Mobilization Does Not Improve Outcome in Patients Transplanted for Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1165-1165
Author(s):  
David Dingli ◽  
Grzegorz S. Nowakowski ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Cell Labeling ◽  
High Dose ◽  
Significant Activity ◽  
Time To Progression ◽  
Hematopoietic Stem ◽  
Myeloma Cells ◽  
The Impact

Abstract Patients with multiple myeloma (MM) who undergo high dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) and achieve a complete response (CR) have a superior overall survival (OS) and time to progression (TTP). Thus achieving a CR is an important goal of therapy with ASCT. Cyclophosphamide has significant activity against MM and is often used in high doses prior to ASCT for mobilization of hematopoietic stem cells. We hypothesized that high dose cyclophosphamide (HDC) may further improve CR rates in patients undergoing ASCT. Methods: The Mayo Clinic myeloma transplant database was searched for patients without circulating myeloma cells who had stem cell mobilization with hematopoietic growth factor (HGF) alone or HDC followed by HGF. Relevant demographic, clinical and laboratory characteristics were abstracted. The main outcome studied was the impact of HDC on CR rates and time to progression (TTP) to myeloma. Results: We identified 201 patients without circulating myeloma cells. Of these, 127 were mobilized with HDC and HGF and 74 with HGF alone. The two cohorts were similar with respect to age, gender, isotype, B2M, plasma cell labeling index, cytogenetics, conditioning regimen, disease status at time of transplant with no statistically significant differences between the two cohorts. CR rates were 37.4 and 41.3% (p=0.6115) for patients mobilized with HDC/HGF and HGF respectively. TTP was 19.9 and 17.6 months (p=0.6039) respectively. The median number of collection sessions for patients mobilized with HDC/HGF was 2 (1–10) and those mobilized with HGF was 4 (1–10) (p<0.0001). In a multivariate analysis for TTP, cytogenetics and achieving a CR were the only independent variables (p=0.0012 and p<0.0001). Conclusion: HDC for autologous hematopoietic stem cell collection reduces the number of collections necessary to support HDT/ASCT. However, HDC does not increase CR rates or improve on TTP for patients undergoing ASCT.

Pretransplatation PET as Major Prognostic Discriminant in IGEV (ifosfamide, gemcitabine, vinorelbine and prednisone) Treated Patients with Relapsed/Refractory Hodgkin's Lymphoma (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3707-3707
Author(s):  
Rita Mazza ◽  
Stefano Luminari ◽  
Massimo Magagnoli ◽  
Michele Spina ◽  
Teodoro Chisesi ◽  
...  
Keyword(s):  
Complete Remission ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Response To Therapy ◽  
High Dose ◽  
Bulky Disease ◽  
The Impact

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High-Dose Therapy and Autologous Hematopoietic Progenitor Cells Transplantation for Recurrent or Refractory Hodgkin's Lymphoma: Analysis of King Hussein Cancer Center Results and Prognostic Variables

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Fawzi Abdel-Rahman ◽  
Ayad Hussein ◽  
Mohammad Aljamily ◽  
Abdulhadi Al-Zaben ◽  
Nilly Hussein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hodgkin's Lymphoma ◽  
Cancer Center ◽  
High Dose ◽  
The Impact

Purpose. to evaluate the outcome of patients with Hodgkin’s lymphoma who underwent autologous transplantation at KHCC bone marrow transplant program. Patients and Methods. Over 6 years, 63 patients with relapsed or refractory Hodgkin’s lymphoma underwent high dose chemotherapy followed by autologous transplant. There were 25.4% patients in complete remission (CR), 71.4% with chemotherapy responsive disease at the time of transplant. Prior to conditioning regimen, 56% received two chemotherapy lines, and, 44% received more than two lines. Results. The main outcomes of the study are the rate of complete remission at day 100, overall survival (OS), relapse-free survival (RFS), The impact of the following variables on OS and RFS: (a) disease status at the time of transplant, (b) number of chemotherapy lines prior to conditioning, (c) age group, (d) time of relapse < or >12 months were investigated. The CR at day 100 was 57%. The median overall survival for the whole group was 40.6 months; the median RFS was 20 months. The only factor which significantly impacts the study outcomes was the number of chemotherapy lines prior to conditioning on OS in favor of patients received two lines. Conclusion. In our study only the number of chemotherapy lines received before conditioning had statistically significant impact on OS.

Requirements for operational cure in multiple myeloma

Blood ◽  
2021 ◽  
Author(s):  
Mohamad Mohty ◽  
Hervé Avet-Loiseau ◽  
Jean-Luc Harousseau
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Limit Of Detection ◽  
Autologous Transplantation ◽  
Significant Proportion ◽  
Response To Treatment ◽  
High Dose ◽  
Duration Of Treatment ◽  
The Impact

Multiple myeloma is usually considered as an incurable disease. However, with the therapeutic improvement observed in the last few years, achievement of an "operational" cure is increasingly becoming a realistic goal. The advent of novel agents, with or without high-dose chemotherapy and autologous transplantation, uncovered a correlation between the depth of response to treatment and the outcome. Of note, minimal residual disease (MRD) negativity is increasingly shown to be associated with improved progression-free survival (PFS), and MRD status is becoming a well-established and strong prognostic factor. Here, we discuss the impact of MRD negativity on PFS and long-term disease control, as a surrogate for a potential cure in a significant proportion of patients. The MRD value and impact should be examined by focusing on different parameters: (i) sensitivity or lower limit of detection level (method used); (ii) timing of assessment and sustainability (iii) type and duration of treatment; (iv) initial prognostic factors (most importantly, cytogenetics) and (v) patient age. Currently, the highest probability of an operational cure is in younger patients receiving the most active drugs, in combination with autologous transplantation followed by maintenance therapy. Older patients are also likely to achieve operational cure, especially if they are treated upfront with an anti-CD38 antibody-based therapy, but also with novel immunotherapies in future protocols. The incorporation of MRD as a surrogate endpoint in clinical trials, would allow the shortening of these, leading to more personalised management, and achievement of long-term cure.

scholarly journals The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma

2001 ◽  
Vol 112 (3) ◽  
pp. 814-819 ◽  
Author(s):  
Faith E. Davies ◽  
Peter D. Forsyth ◽  
Andrew C. Rawstron ◽  
Roger G. Owen ◽  
Guy Pratt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Disease State ◽  
High Dose ◽  
Minimal Disease ◽  
High Dose Melphalan ◽  
The Impact

Superiority of Double over Single Autologous Stem Cell Transplantation as First-Line Therapy for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 536-536 ◽  
Author(s):  
Michele Cavo ◽  
Claudia Cellini ◽  
Elena Zamagni ◽  
Patrizia Tosi ◽  
Delia Cangini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Autologous Transplantation ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
The Impact

Abstract The “Bologna 96” clinical trial was designed in an attempt to prospectively compare a single autologous transplantation (Tx-1) versus double autologous transplantation (Tx-2) as part of first-line therapy for patients with symptomatic multiple myeloma (MM) and less than 60 years of age. Tx-1 was given to support melphalan 200 mg/m2 (MEL-200); Tx-2 was given to support a first course of MEL-200 followed, within 3 to 6 months, by melphalan 120 mg/m2 + busulfan 12 mg/kg. In both arms of the study, autologous transplantation was preceded by 4 courses of VAD and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide 7 g/m2. An analysis was performed using an intent-to-treat approach on 228 patients who were randomly assigned to Tx-1 (n=115 patients, median follow-up of living patients: 45 months) or Tx-2 (n=113 patients, median follow-up of living patients: 54 months). In comparison with Tx-1, Tx-2 prolonged event-free survival (EFS) of 12 months (P=0.001) and time to progression (TTP) of 17 months (P=0.0001). Six-year projected probability of survival (OS) was 44% for Tx-1 and 63% for Tx-2 (P=0.3). The probability of attaining stringently defined complete remission (CR) or near complete remission (nCR) was 35% for Tx-1 and 48% for Tx-2; the sample size analyzed was not powered to detect a statistically significant difference between the two groups. Among patients randomized to Tx-1, attainment of CR or nCR was an essential prerequisite for extended OS (P=0.0001), EFS (P=0.000002) and TTP (P=0.000007). At the opposite, the benefits of double autologous transplantation were the greatest among patients who failed at least nCR. In particular, patients who did not attain CR or nCR after the first autologous transplantation and by study randomization received a second transplantation had a significantly longer duration of OS (P=0.01), EFS (P=0.000006) and TTP (P=0.000001) than patients who had the same response status but were assigned to receive a single autologous transplantation. Compared to Tx-1, Tx-2 significantly extended OS (P=0.04), EFS (P=0.000006) and TTP (P=0.000001) also among patients who failed Cr or nCR after receiving the entire treatment program to whom they were assigned (Tx-1 or Tx-2). At the opposite, for patients who were in CR or nCR after the first transplantation, there was no significant benefit from receiving a second autologous transplantation. In conclusion, data from the present analysis show that in comparison with a single autologous transplantation, i) double transplantation significantly prolonged EFS and TTP among younger (< 60 years) patients with previously untreated MM; ii) double autologous transplantation was of particular benefit for patients who failed at least nCR. Mature data derived from the final analysis of the study must be awaited before definite conclusions can be given concerning the impact of double autologous transplantation on the outcome of patients with MM. Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.Cavo); Ministero dell’Università e Ricerca Scientifica, progetto FIRB, RBAU012E9A_001 (M. Cavo); and Fondazione Carisbo.

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