scholarly journals RVD induction and autologous stem cell transplantation followed by lenalidomide maintenance in newly diagnosed multiple myeloma: a phase 2 study of the Finnish Myeloma Group

2019 ◽  
Vol 98 (12) ◽  
pp. 2781-2792 ◽  
Author(s):  
Sini Luoma ◽  
Pekka Anttila ◽  
Marjaana Säily ◽  
Tuija Lundan ◽  
Jouni Heiskanen ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Maintenance Phase ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients

Abstract Autologous stem cell transplantation (ASCT) combined with novel agents is the standard treatment for transplant-eligible, newly diagnosed myeloma (NDMM) patients. Lenalidomide is approved for maintenance after ASCT until progression, although the optimal duration of maintenance is unknown. In this trial, 80 patients with NDMM received three cycles of lenalidomide, bortezomib, and dexamethasone followed by ASCT and lenalidomide maintenance until progression or toxicity. The primary endpoint was the proportion of flow-negative patients. Molecular response was assessed if patients were flow-negative or in stringent complete response (sCR). By intention to treat, the overall response rate was 89%. Neither median progression-free survival nor overall survival (OS) has been reached. The OS at 3 years was 83%. Flow-negativity was reached in 53% and PCR-negativity in 28% of the patients. With a median follow-up of 27 months, 29 (36%) patients are still on lenalidomide and 66% of them have sustained flow-negativity. Lenalidomide maintenance phase was reached in 8/16 high-risk patients but seven of them have progressed after a median of only 6 months. In low- or standard-risk patients, the outcome was promising, but high-risk patients need more effective treatment approach. Flow-negativity with the conventional flow was an independent predictor for longer PFS.

Rapid Risk-Profiling Including Fast Donor Search within a Multi-Center Trial Allows for Early Allogeneic Stem Cell Transplantation during Aplasia in Patients with High-Risk Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2767-2767 ◽  
Author(s):  
Markus Andreas Schaich ◽  
Monika Fuessel ◽  
Martin Bornhaeuser ◽  
Christian Thiede ◽  
Brigitte Mohr ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
High Risk Patients ◽  
Risk Profiling ◽  
Risk Patients

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing allogeneic HSCT within induction therapy can circumvent these problems and may furthermore reduce cumulative toxicity in high risk patients. Therefore, the prospective randomized treatment trial AML2003 for patients <= 60 years was set up, to investigate the feasibility and value of an intensified treatment strategy, i.e. early allogeneic stem cell transplantation in aplasia after induction therapy, for high risk AML patients in a multi-center setting. To achieve this goal, rapid analysis of cytogenetics, FLT3 status and HLA-types of the patient and possible family donors is of utmost importance. This fast search diagnostics together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. Furthermore, in all patients the likelihood to find an unrelated donor is checked by an internet search in the BMDW database. Within the first 8 months 107 AML patients with a median age of 48 (17–60) years were included in the study. Fast search diagnostics was complete within a median of 15 (range 5–31) days after arrival of the bone marrow samples for all patients. 57/107 patients were randomized into the intensified treatment arms. Out of these 25 (44%) patients with high risk characteristics have been identified. A suitable related or unrelated donor was found for 22 (88%) of those high-risk patients. Nine of those high risk patients with a donor (41%) received early allogeneic stem cell transplantation in aplasia after the first (n=4) or the second (n=5) induction therapy course on an intend to treat basis within the protocol. Three were transplanted with stem cells of related and six of unrelated donors. The preparative regimen consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. So far no treatment associated death had to be recognized. These encouraging preliminary results show that fast risk-profiling and early donor-search is feasible in a large multi-center study. This leads to a significant proportion of early allogeneic stem cell transplants in aplasia after induction therapy within the group of high risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

Upfront Allogeneic Stem Cell Transplantation for Remission Induction in High-Risk Acute Myeloid Leukemia Patients within the Randomized Multi- Center Trial AML2003.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 978-978 ◽  
Author(s):  
Markus Schaich ◽  
Thomas Illmer ◽  
Walter E. Aulitzky ◽  
Martin Bornhaeuser ◽  
Martin Griesshammer ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Allogeneic Transplantation ◽  
Remission Induction ◽  
High Risk Patients ◽  
Risk Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing upfront allogeneic HSCT for remission induction as part of induction therapy has the potential to circumvent these problems and might furthermore reduce cumulative toxicity in high-risk patients. Therefore, in 2003 we started a prospective multicenter randomized trial that investigates both the feasibility and efficacy of upfront allogeneic stem cell transplantation for remission induction in high-risk AML patients. Methods: The AML2003 study compares in a randomized fashion an intensified treatment approach using upfront allogeneic transplantation in high risk patients as part of the induction therapy (IT) during marrow aplasia achieved by DA (daunorubicin 60 mg/ m2 – day 3–5; cytarabine 100 mg/m2 – day1–7) to a “conventional” treatment strategy, which allows for allogeneic transplantation only in patients achieving remission after two induction courses (DA). To do this, rapid analysis of cytogenetics, FLT3 status and HLA-DNA-typing of the patient and possible family donors is of utmost importance. This “fast search diagnostics” together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. The dose-reduced preparative regimen for upfront allogeneic stem cell transplantation within induction therapy consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. Results: Until the last update we recruited 679 patients <= 60 years with de novo (n=570) or secondary (n=109) AML. Out of 340 patients randomized for an intensified treatment approach we identified 139 patients (41%) with high-risk defined by cytogenetic criteria (n=87), FLT3 status (n=15) or day 15 blast count (n=37). Fast search strategy revealed HLA identical donors (related or unrelated) for 106 patients. Consequently, 78 high-risk AML patients assigned to the intensified treatment strategy received allogeneic transplantation. Upfront allogeneic stem cell transplantation for remission induction was feasible in 28 high-risk AML patients during marrow aplasia after IT1 (n=10) or IT2 (n=18), respectively. Fifteen of these patients received unrelated grafts. Conclusions: These preliminary results show that rapid risk profiling and fast donor-search is feasible in a large multi-center study. This leads to a significant proportion of upfront allogeneic stem cell transplants as part of the induction therapy within the group of high-risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

A cost and resource utilization analysis of micafungin bridging for hemato-oncological high-risk patients undergoing allogeneic stem cell transplantation

2015 ◽  
Vol 94 (6) ◽  
pp. 526-531 ◽  
Author(s):  
Sebastian M. Heimann ◽  
Maria J.G.T. Vehreschild ◽  
Oliver A. Cornely ◽  
Bernd Franke ◽  
Michael von Bergwelt-Baildon ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Resource Utilization ◽  
Allogeneic Stem Cell Transplantation ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals Newly Diagnosed Myeloma (MM) Patients (Pts) with High-Risk (HR) Cytogenetics By FISH: Is There a Role for Tandem Autologous Stem Cell Transplantation (ASCT)?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3176-3176
Author(s):  
Sara Farshchi-Zarabi ◽  
Gurdeep Parmar ◽  
Esther Masih-Khan ◽  
Sophia Farooki ◽  
Christine Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Cancer Centre

Abstract Background: Recent analyses have suggested that newly diagnosed multiple myeloma (MM) patients with the high-risk (HR) chromosomal abnormalities del 17p and t(4;14) detected by FISH may benefit from bortezomib (BTZ)-based induction therapy and tandem autologous stem cell transplantation (ASCT) (Sonneveld P et al, J Clin Oncol 2013;31: 3279). At Princess Margaret Cancer Centre, we have offered upfront tandem ASCT for HR pts with del 17p, t(4;14) and/or t(14;16) and now retrospectively review the results of this approach. Methods: After obtaining Institutional Research Ethics Board approval, we used Princess Margaret Myeloma Database to identify HR MM pts who underwent tandem ASCT between June 2005 and January 2015. We performed a retrospective chart review to investigate the survival outcome of this group of patients. Results: Between 06/05 and 01/15, 52 HR pts underwent tandem ASCT at Princess Margaret Cancer Centre. 21 had del 17p, 20 had t(4;14), 5 had t(14;16), 3 had both t(4;14) + del 17p and 3 had both t(14;16) + del 17p. Median age was 56.5 yrs (range 31-71); 34 were male. ISS stage was I in 12, II in 15, III in 12 and N/A in 13 pts. The majority (42 pts) received BTZ-based induction therapy which consisted of CyBorD in 38; 11 pts required a 2nd regimen before ASCT. The median time from diagnosis to 1st ASCT was 6.7 mos (range 4.8 -45.7) and the median time between transplants was 3.7 mos (range 0.9- 6.6); 30 pts received lenalidomide (len) between ASCTs to prevent early relapse. All but 2 pts (96%) received maintenance therapy after the 2nd ASCT which included thalidomide in 7 (13%), len +/- steroids in 39 (75%) and BTZ +/- len in 4 (8%) of all pts. Thirty-six (69%) received both BTZ-based induction and len maintenance after the 2nd ASCT. No transplant-related deaths occurred. Median follow-up is 26.3 mos (range 9.1 to 104.3). The median overall survival in all 52 pts from diagnosis was 31.1 mos (range 11.9 to 110.8) with a median PFS of 24.0 mos (9.1 to 83.6); median survival after progression was only 8.2 mos (0.1-62.8) mos in the 16 pts who relapsed after the 2nd ASCT.Table 1.HR Group#Calculated from diagnosisCalculated from 2nd ASCTMedian PFS, mos (range)Median OS, mos (range)Median PFS, mos (range)Median OS, mos (range)t(4;14)2322.4 (11.4-58.1)29.9 (17.7-84.4)7.0 (0.2-23.5)17.3 (5.4-73.6)Del 17p2724.4 (9.1-83.6)35.0 (11.9-110.8)11.2 (1.3-69.4)25.3 (3.8-99.6)t(14;16)827.4 (10.3-55.4)30.6 (11.9-55.4)16.9 (2.2-48.1)19.7 (3.8-48.1)Both BTZ-induction + len maint3622.2 (10.3-55.4)30.5 (11.9-67.5)8.1 (1.4-48.1)18.7 (3.8-57)No BTZ-induction + len maint1627.2 (9.1-83.6)49.5 (22.0-110.8)12.1 (0.2-69.4)24.5 (6.9-99.6) Conclusions: 1) MM pts with HR cytogenetics, particularly those with t(4;14), have a short PFS and OS after tandem ASCT; 2) even following BTZ-based induction therapy and len maintenance, outcomes with tandem ASCT are suboptimal in HR pts; 3) further investigations are necessary to identify novel strategies for the management of HR MM in the era of modern therapeutic agents. Disclosures Chen: Celgene: Consultancy, Honoraria, Research Funding. Kukreti:Janssen Ortho: Honoraria; Roche: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Tiedemann:Janssen Ortho: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Trudel:Oncoethix: Research Funding; Novartis: Honoraria; Trillium Therapeutics Inc.: Research Funding; BMS: Honoraria; Amgen: Honoraria, Speakers Bureau; Celgene: Equity Ownership, Honoraria, Speakers Bureau. Reece:Lundbeck: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Otsuka: Research Funding; Merck: Research Funding; Millennium Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria; Onyx: Consultancy; Janssen-Cilag: Consultancy, Honoraria, Research Funding.

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