Long-term results in multiple myeloma treated with high-dose melphalan and autologous peripheral stem cell transplantation and achieving complete remission.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18564-e18564
Author(s):  
Massimo Vincenzo Martino ◽  
Maurizio Postorino ◽  
Giuseppe Alberto Gallo ◽  
Giuseppe Irrera ◽  
Eugenio Piro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Long Term Results ◽  
Cumulative Probability ◽  
High Dose ◽  
Probability Of Survival ◽  
High Dose Melphalan

e18564 Background: Major progress has been made in the treatment of multiple myeloma (MM) in recent years, including the introduction of novel agents and transplant strategy. High-dose melphalan (HDM) followed by autologous haematopoietic stell cell transplantation (AHSCT) remains an integral component of upfront treatment strategy. Many studies stress the importance of achieving a deeper response as a surrogate for improved survival but, despite the improvements, MM remains incurable and long-term survival appears elusive. The aim of study is to establish the actual prognosis for the different response categories in the same original cohort of patients with MM treated with HDM and AHSCT after long-term follow-up. Methods: We evaluated a cohort of MM patients treated up-front in the Bone Marrow Transplant Unit of Reggio Calabria between 1994 and 2006. Disease response was assessed with the use of criteria from the European Group for Blood and Marrow Transplantation modified to include Complete Remission (CR) and near Complete Remission (nCR). Results: The study group was composed by 150 patients (age at 1st AHSCT M±SD 55±9 years, male 64%); 94 (63%) of them had 2 AHSCT. After treatments 22 (15%) patients have a CR, 32 (21%) a nCR and 90(64.0%) a PR. After a mean follow up of 50 months the cumulative probability of survival was 69% for patients with CR, 43% for those in nCR and 0% for patients in PR (log-rank test P PR vs nCR=0.006; CR vs nCR and nCR vs PR<0.001 ). The estimate mean survival for patients with CR, nCR and PR was respectively 166, 81 and 46 months. For patients with CR the survival curves showed a plateau of cumulative probability of survival after 134 months. Conclusions: In MM achieving a CR after HDM and AHSCT is a central prognostic factor. The relapse rate is low in patients with >11 years of follow-up, possibly signifying durable remission in patients in CR.

Long-term follow-up of autotransplant (AT)-supported high-dose melphalan (hdm) for multiple myeloma (MM): Update of Intergroup Francophone du Myelome (IFM), Southwest Oncology Group (SWOG), and Arkansas (ARK) Total Therapy (TT) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8519-8519
Author(s):  
B. Barlogie ◽  
M. Attal ◽  
J. Crowley ◽  
J. Harousseau
Keyword(s):  
Phase Iii ◽  
Long Term Results ◽  
High Dose ◽  
Long Term Follow Up ◽  
Phase Iii Trials ◽  
Trial Outcomes ◽  
Total Therapy ◽  
High Dose Melphalan

8519 Background: Clinical trial outcomes are usually published when statistical protocol objectives have been met, with short median follow-up not exceeding 5 years. Due to treatment innovations, MM survival beyond 10 years has become more common but formal long-term results are seldom reported. Methods: IFM, SWOG and ARK provide an update of their major trials. IFM-90: 1 AT v standard therapy (STD), IFM-94: 2 v 1 AT, IFM-9902: 2AT ± THAL, IFM-9904: 2AT for high-risk MM; SWOG-9321: 1 AT v STD; TT1: 2 AT with interferon, TT2: 2AT ± THAL, TT3: 2AT + THAL + bortezomib. Results: OS clustered in 3 groups with superior outcomes for TT3/TT2/IFM-99 v TT1 v IFM-94/ IFM-90/SWOG-9321 with 5/10/15-yr estimates of 70%/50%/TE v 57%/35%/20% v 43%/25%/15% (p<0.0001). EFS also clustered in 3 groups with superior outcomes for TT3 v TT2 v remainder with estimates of 71%/TE/TE v 50%/35%/TE v 27%/ 15%/10% (p<0.0001). Among phase III trials, added THAL in TT2 increased 10-yr OS/EFS from 40%/25% to 60%/40% (p=0.04/p=0.0005); 10-yr OS was 30% v 8% with 1 v 0 AT in IFM-90 (p=0.005), 31% v 21% with 2 AT v 1 AT in IFM-94 (p=0.08), and 20% for both arms of S9321. On multivariate analysis involving 2962 patients, OS was adversely affected by B2M >=3.5mg/L (p<0.001), LDH >=ULN (p<0.001), hemoglobin <10g/dL (p=0.001) and albumin <3.5g/dL (p=0.02). 2AT (65%) and THAL (21%) both contributed independently to superior OS (p<0.001, p=0.002); among individual trials, IFM-9902 (19%) and TT2/TT3 (33%) both improved OS significantly (both p<0.001). For each of the 3 major OS clusters, 228 patients could be matched on B2M, LDH, hemoglobin and albumin, with 10-yr OS/EFS estimates of 65%/30% for the TT3/TT2/IFM-9902 group significantly exceeding 30%/15% each for the other 2 groups (p=0.001/p=0.001). Conclusions: A 15-yr EFS plateau of 10% with older trials and superior 10-yr EFS/OS estimates of 50%/35% with recent studies emphasize that cure should be a realistic trial objective in contemporary MM therapy, requiring however very long-term follow-up beyond 15 years. [Table: see text]

Long-Term Results in Multiple Myeloma After High-Dose Melphalan and Autologous Transplantation According to Response Categories in the Era of Old Drugs

2014 ◽  
Vol 14 (2) ◽  
pp. 148-154 ◽  
Author(s):  
Massimo Martino ◽  
Maurizio Postorino ◽  
Giuseppe Alberto Gallo ◽  
Giuseppe Messina ◽  
Santo Neri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Long Term Results ◽  
High Dose ◽  
High Dose Melphalan ◽  
Old Drugs

Durable Responses to Lenalidomide (Revlimid®) in Patients with AL Amyloidosis: Follow Up of a Phase II Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 192-192 ◽  
Author(s):  
David C. Seldin ◽  
Michael Rosenzweig ◽  
Kathleen T. Finn ◽  
Salli Fennessey ◽  
Anthony Shelton ◽  
...  
Keyword(s):  
Long Term Results ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Al Amyloidosis ◽  
Treatment Protocols ◽  
Results Of Treatment ◽  
Kaplan Meier ◽  
High Dose Melphalan

Abstract AL amyloidosis is a clonal plasma cell dyscrasia in which misfolded immunoglobulin light chains deposit in tissues and produce organ failure and death. Untreated, median survival is short. Melphalan-based regimens can produce hematologic remissions and improvement in organ function; more than 20% of patients treated with high dose melphalan and autologous stem cell transplantation (HDM/SCT) have survived more than 10 years (Blood, in press). The combination of lenalidomide and dexamethasone can also produce partial and complete hematologic responses (Blood2007;109:492–496). Here we report on remission duration and long-term results of treatment in the original 34 patients and an additional 9 patients, with median follow up of 26.5 m. The median age of the 43 patients was 64 (range, 44–84), 70% were male, 67% were lambda isotype, 46% had multi-organ involvement, and 42% had cardiac involvement. 90% had received prior melphalan-based therapy; in 60% this was HDM/SCT. 14% of patients had received thalidomide and 5%, bortezomib. 10% had no prior treatment. Patients were begun at 15 mg lenalidomide per day for 21 days per month; the median tolerated dose was 10 mg. The response rate was 60% (24% CR, 36% PR); an additional 15% of patients had minor responses. Of the 8 patients who achieved a CR, 6 occurred at 3–6 months of treatment, but 2 were late (18m, 19m). 7 of 8 are alive; one died of cardiac allograft rejection. 3 of 8 have relapsed. 5 of 8 maintain remissions for 6–30 m, of which 4 of 8 continue in CR off therapy for 6–21m. Kaplan-Meier survival for all 43 patients is shown. 7 of 8 patients achieving CR had significant proteinuria: in 2 patients (29%), proteinuria resolved (2 g to 120 mg, 8.8 g to 140 mg); in 3 (43%) it improved by 50% or more; and in 2 there has been no change. Thus, lenalidomide can produce beneficial hematologic and organ responses in AL amyloidosis patients, and remissions can be durable off therapy. Further trials should be done to determine how and when to incorporate lenalidomide into treatment protocols for AL amyloidosis. Figure Figure

Reduced-Intensity Conditioning for Allograft (RICT) after Cytoreductive Autograft (ASCT) in Relapsed/Resistant Hodgkin’s Lymphoma (HL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3294-3294
Author(s):  
A. M. Carella ◽  
E. Todisco ◽  
L. Castagna ◽  
A. Santoro ◽  
G. Catania ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Complete Remission ◽  
Long Term Results ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
High Dose Therapy ◽  
Previous Therapy ◽  
Reduced Intensity

Abstract Reduced-intensity conditioning for transplant (RICT) aims to exploit graft vs lymphoma (GvLy) effects while reducing conditioning-related toxicity. Because GvLy responses might be insufficient when HL are bulky and lymphoma growth is rapid, we pionered that intensive cytoreduction prior to RICT may allow GvLy reaction to be exploited (Carella et al. JCO2000; 18:3918). Thirty-eight patients with relapsed (n=26) or refractory (n=12) HL underwent RICT from an HLA-identical sibling preceeded by ASCT. Previous therapy consisted of 2–6 lines. High-dose therapy with ASCT consisted of BEAM protocol (n=29) or melphalan 200 mg/m2 (n=9). RICT consisted of fludarabine-cyclophosphamide (n=30) or fludarabine-melphalan (n=8). The two groups had similar prognostic factors. The median time to neutrophils and platelets recovery was 10 days and 16 days, respectively. Chimerism studies indicated 100% donor-derived engraftment. Day 100 and cumulative (2 yrs) TRM were 5,3 % (2 pts) and 18% (7 pts), respectively. Seventeen patients (44%) are alive (12 in complete remission and 5 with stable disease) with a median follow-up of 41 months (7–110 months). Twenty-one patients expired (TRM n=7, disease progression n=14). In conclusion, tandem ASCT/RICT is feasible and effective salvage therapy for patients with advanced HL. The long-term results obtained appear encouraging.

scholarly journals Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6721-6727 ◽  
Author(s):  
Luisa Giaccone ◽  
Barry Storer ◽  
Francesca Patriarca ◽  
Marcello Rotta ◽  
Roberto Sorasio ◽  
...  
Keyword(s):  
Complete Remission ◽  
New Drugs ◽  
High Dose ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
High Dose Melphalan

Abstract Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed myeloma patients was based on the presence or absence of HLA-identical siblings. First-line treatments included a cytoreductive autograft followed by a nonmyeloablative allograft or a second melphalan-based autograft. Here, we report long-term clinical outcomes and discuss them in the light of the recent remarkable advancements in the treatment of myeloma. After a median follow-up of 7 years, median overall survival (OS) was not reached (P = .001) and event-free survival (EFS) was 2.8 years (P = .005) for 80 patients with HLA-identical siblings and 4.25 and 2.4 years for 82 without, respectively. Median OS was not reached (P = .02) and EFS was 39 months (P = .02) in the 58 patients who received a nonmyeloablative allograft whereas OS was 5.3 years and EFS 33 months in the 46 who received 2 high-dose melphalan autografts. Among patients who reached complete remission in these 2 cohorts, 53% and 19% are in continuous complete remission. Among relapsed patients rescued with “new drugs,” median OS from the start of salvage therapy was not reached and was 1.7 (P = .01) years, respectively. Allografting conferred a long-term survival and disease-free advantage over standard autografting in this comparative study.

scholarly journals Extending Autologous Hematopoietic Stem Cell Transplantation As First Line Treatment in Multiple Myeloma Patients with Severe Renal Impairment: A Retrospective Study of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4637-4637 ◽  
Author(s):  
Karine Augeul-Meunier ◽  
Denis Caillot ◽  
Anne-Marie Stoppa ◽  
Lionel Karlin ◽  
Lofti Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Renal Impairment ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
High Dose ◽  
Advisory Committees ◽  
High Dose Melphalan

Abstract Introduction Renal impairment occurs in 20-30% of newly diagnosed multiple myeloma patients, requiring dialysis for up to 10% of patients.Recent results ofan IFM (Intergroupe Francophone du Myélome) study confirm the effectiveness of high dose melphalan followed by Autologous Hematopoietic Stem Cell Transplantation (ASCT) as first line therapy in multiple myeloma patients. Most centers exclude renal failure patients due to concerns of toxity, because data are limited for safety and toxicity to consider. This current retrospective study observes toxicity and outcome in 55 multiple myeloma patients with severe renal impairment, undergoing high dose melphalan and ASCT, in the age of bortezomib. Methods Using the PROMISE database, 55 multiple myeloma patients French SFGM-TC centers were included from January 2002 to November 2012. Characteristics of the patients presenting with creatinine clearance less than 30ml/min at time of ASCT were included. Results Median age was 61 (40-75) years old. Thirty-nine (71%) presented free light chain myeloma. Twenty-three (42%) patients were on dialysis at the time of ASCT and during hospitalization. Thirty-one (56%) patients received bortezomib as induction therapy. Melphalan dose ranged from 75mg/m² to 200mg/m². Thirty (55%) patients were treated with a dose of 140mg/m². Median delay between diagnosis and ASCT was 5.3 months. Among 50 patients evaluated for toxicity, respectively febrile neutropenia and mucositis occurred in 92% and 90% of patients. Half of the mucositiscases were grade 3-4. The median number of days before neutrophil and platelet recovery was respectively 12 days (10 - 34) and 16 days (7 - 331). Two patients experienced cardiac toxicity (grade 1-2), and 4 patients neurologic toxicity (grade 3 for one patient). Among 51 patients evaluated for response, 12 patients (24%) were at least in Very Good Partial Response (VGPR) before ASCT, including 5 in Complete Response (CR). All of them were treated with bortezomib as induction therapy. After ASCT, 30 patients (58.8%) reached at least VGPR (22 CR and 8 VGPR). Among 30 patients in VGPR or more post ASCT, 22 (73%) were treated with bortezomib before ASCT. Table 1 shows the responses. Fourteen (26%) received two ASCT. One patient died from toxicity (cerebral bleeding during second ASCT). There is no argument for dramatic response improvement with this procedure in comparison to single ASCT. After a median follow-up of 55 months, median progression free survival (PFS) was 55 months, and median overall survival (OS) was 95 months. In multivariate analysis, dose of melphalan at 140mg/m² was significantly correlated with a better PFS (p=0.006), compared to 100mg/m² (or less) and to 200mg/m². During follow-up 29 patients (54%) relapsed and 25 died. The main causes of death were relapse and disease progression (72%). There were only 3 cases of treatment related mortality (TRM). At day 100, the cumulative incidence of TRM was 6%. Among 23 dialysis patients, 6 patients (26%) became dialysis independent, but not during ASCT. Thirteen (56%) were still alive at last follow-up, and 8 (34%) experienced relapse. Median PFS for this subgroup of patients was 73 months. Conclusion With an acceptable TRM, without major toxicities, high dose melphalan (140mg/m²) following by ASCT appears to be a real benefit for multiple myeloma patients with severe renal failure. This includes patients on dialysis. Response is dramatically improved by this procedure, with median PFS similar to that of patients with normal renal function. Finally, adjunction of bortezomib as induction therapy also improves the efficacy of ASCT. Disclosures Augeul-Meunier: gilead: Consultancy; janssen: Consultancy. Karlin:amgen: Consultancy, Honoraria; janssen-cilag: Consultancy, Honoraria; celgene: Consultancy, Honoraria; Bristol: Consultancy; takeda: Consultancy. Benboubker:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau:sanofi: Consultancy; amgen: Consultancy; janssen: Consultancy; celgene: Consultancy.

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