Updates on safety and efficacy of maintenance therapy after autologous stem cell transplantation in newly diagnosed multiple myeloma: A systematic review.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20503-e20503
Author(s):  
Ahsan Wahab ◽  
Kamran Mushtaq ◽  
Maria Khakwani ◽  
Aqsa Khan ◽  
Afia Ashraf ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Combination Therapy ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
High Risk Patients ◽  
Risk Patients ◽  
Dose Reductions

e20503 Background: Multiple Myeloma (MM) is treatable but an incurable hematological malignancy, requiring additional approaches such as maintenance therapy (MT) after autologous-stem cell transplantation. MT aids to achieve deepened response, sustained response and prolongs progression-free survival (PFS) but has a controversy over its overall survival (OS) benefit. Within the last decade, there have been innovative efforts tested for MT. We designed a systematic review to evaluate the current evidence on this topic. Methods: PubMed and Embase were searched for articles published on MT between 01/2010 and 12/2018 and PRISMA guidelines were used to evaluate 76,588 articles on PubMed and 1516 articles on Embase. Thirty-three articles were included in systematic review. Results: Thirteen articles were available on lenalidomide-MT whereas six articles each on thalidomide and proteasome inhibitors, five articles on combination therapy, two articles on miscellaneous and one article on elotuzumab were available, including trials and observational studies. MT (thalidomide 50 mg, lenalidomide 10 mg) was given for a variable period, commonly used till relapse, progression or unacceptable toxicity. Thalidomide showed consistent PFS-benefit but no OS benefit and had significant neurotoxicity, responsible for discontinuations or dose reductions. Lenalidomide had evidence for both, improved PFS and some evidence for better OS and had hematotoxicity, mainly neutropenia which required dose reductions. Secondary primary malignancies were more frequent with lenalidomide. Longer maintenance of lenalidomide was associated with more toxicity. Thalidomide-bortezomib combination had better PFS than thalidomide alone but no OS benefit. Bortezomib-MT improved OS in high-risk patients and renal failure and had dose-dependent toxicity. Bortezomib-MT after bortezomib-based induction was better than thalidomide-based-MT after cytotoxic induction. MT was associated with the achievement of negative MRD-status. Ixazomib was effective and feasible with improved PFS. Combination of bortezomib-lenalidomide-dexamethasone MT was beneficial in high-risk patients. Conclusions: MT improves PFS with limited evidence toward improved OS. For better outcomes, lenalidomide-based-MT should be given routinely; adjustment of dose might be required due to neutropenia. High-risk patients can get benefit from combination therapy. Role of combination MT needs to be further explored in large prospective studies.

scholarly journals Proteasome Inhibitor or Immunomodulators Which is The Optimal Maintenance For Newly Diagnosed Multiple Myeloma: A 7-Year Real-World Data in China.

2021 ◽  
Author(s):  
Xiaoyan Han ◽  
Chunxiang Jin ◽  
Gaofeng Zheng ◽  
Donghua He ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Maintenance Therapy ◽  
Proteasome Inhibitor ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Real World Data ◽  
High Risk Patients ◽  
Optimal Maintenance ◽  
Risk Patients

Abstract Background: According to different patients’ subgroups choose optimal maintenance therapy. Methods: 226 Newly Diagnosed Multiple Myeloma (NDMM) patients in our center were included, the patients’ characteristics, survival, response, subgroup analysis, adverse reactions were compared between the patients with or without maintenance, proteasome inhibitor (PI) or immunomodulators (IMiDs) maintenance. And the survival of different maintenance duration of bortezomib-based regimens was also analyzed.Results: The maintenance therapy not only upgraded more patients’ response (34.3 vs. 13.3%, p= 0.006), but also significantly prolonged the patients’ PFS (median PFS: 41.1 vs. 10.5 months, p < 0.001) and OS (median OS: not reached vs. 38.6 months, p < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs. 38.5 months, p = 0.034) and OS (median OS: not reached vs. 78.5 months, p = 0.041) can both benefit from bortezomib-based maintenance. The patients younger than 65 years old with bortezomib-based maintenance significantly prolonged the OS (p= 0.032). Patients achieving the only partial response (PR) after induction and consolidation therapy experienced a significantly longer PFS and OS with bortezomib-based maintenance compared to IMiDs (p= 0.007, 0.002). Besides, the high-risk patients (ISS 2-3, DS 2-3 and RISS 2-3) with bortezomib-based maintenance can benefit PFS (p= 0.002, 0.02, 0.06, respectively) and OS (p=0.059, 0.047, 0.044, respectively) compared with IMiDs. The OS was significantly prolonged in the patients who received ≥12 months of bortezomib-based maintenance than those with maintenance < 12 months (p< 0.001), but no difference was observed in OS between the patients who received the 12-24 or ≥ 24months of bortezomib-based maintenance (p= 0.292).Conclusion: Maintenance therapy can significantly improve the survival of NDMM patients. Bortezomib-based regimens maintenance was more superior to IMiDs in overall PFS and OS. The beneficial effect is most evident in patients achieving the only PR after induction and consolidation therapy, and the high-risk patients. Moreover, younger patients also could benefit from bortezomib-based maintenance in OS. The bortezomib-based maintenance duration lasting 12-24 months after induction and consolidation therapy can reach a satisfactory OS.

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.

scholarly journals Is There an Unequal Benefit of Autologous Stem Cell Transplant in Different Cytogenetic Groups of High Risk Patients with Multiple Myeloma: The University of Miami Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Fahmin Basher ◽  
Sandra Sanchez ◽  
Jonathan H. Schatz ◽  
James E. Hoffman ◽  
Lazaros J. Lekakis
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Retrospective Analysis ◽  
Comprehensive Cancer Center ◽  
High Risk Patients ◽  
Risk Patients ◽  
University Of Miami ◽  
The University ◽  
Standard Risk

BACKGROUND: Stratification using cytogenetics (CG), either metaphase karyotyping or fluorescence in situ hybridization (FISH) is used to identify patients (pts) with multiple myeloma (MM) who are at higher risk of relapse and tend to have poorer survival. It is largely unknown if autologous stem cell transplantation (auto-HCT) after high dose melphalan (200 mg/m2) is able to modify the survival of some of these high-risk MM pts and to make it comparable to standard risk. METHODS: Pts were classified as high risk (HR) if either conventional cytogenetics or FISH demonstrated at least one of the following 1q+, 1p-, 17p-, 13q-, t(4;14), or t(14;16), realizing that the inclusion of 13q- by FISH alone and 1p- in the HR MM definition is controversial. Pts with normal chromosomes or those with trisomies and hyperdiploidy were considered standard-risk (SR). We compared progression-free survival (PFS) and overall survival (OS) via a retrospective analysis of pts at the University of Miami Sylvester Comprehensive Cancer Center who underwent auto-HCT between January 2014 and December 2017 for MM. Survival analyses were performed using the log-rank test, with significance at p-value &lt; 0.05. RESULTS: Male pts comprised 56% of the population, and 40% of pts were of Hispanic ethnicity. Of 205 pts undergoing auto-HCT, 108 (53%) had at least one HR cytogenetic abnormality. Interestingly, the depth of response to pre-transplant induction was higher in pts classified as HR, with 71% (77 of 108) achieving at least a very good partial response (VGPR), while 24% (23 of 96) SR pts achieved VGPR. While OS remained largely unaffected in HR pts (34.0 m vs. 35.1 m, p = 0.27); HR pts had an inferior PFS compared to SR pts (21.9 m vs. 25.7 m, p = 0.041). The presence of trisomies did not negate the poorer PFS of HR pts. When we evaluated specific HR CG abnormalities, OS and PFS in patients with 1q+ or t(4;14) were surprisingly comparable to SR pts, indicating a significant benefit from auto-HCT. On the other hand, OS was significantly decreased in pts with 1p- when compared to standard risk (16.5 m vs. 35.1 m, p = 0.004) or other high-risk patients (16.5 m vs. 35.4 m, p = 0.01), implying that 1p- group derive no benefit from auto-HCT. Similarly, OS was shorter in pts with t(14;16) (16.5 m vs. 34.4 m, p = 0.025) and with 17p- (26.6 m vs. 35.1 m, p=0.01), however the PFS was not affected in these populations. In pts with 13q-, PFS was significantly shorter (20.3 m vs. 25.7 m, p=0.023) compared to SR pts without affecting OS. CONCLUSION: At our center in a retrospective analysis of 205 pts: a) patients with HR MM responded better and faster than SR pts to induction, b) those with 1p- did not derive any benefit from transplant and c) pts with 17p- and t(14;16) had some short term benefit (similar PFS to SR group) but at the end their OS remained inferior. Nevertheless, we consider a very important finding the fact that, by having auto-HCT, pts with 1q+ and t(4;14), equalized their PFS and OS to those of SR pts. Based on these findings, patients with 1q+ and t(4;14) should still have a transplant in CR1 even after optimal induction. Whether 17p- and t(14;16) pts can extend PFS benefit after transplant into OS benefit with maintenance regimens stronger than lenalidomide alone remains to be determined. Disclosures Hoffman: Celgene: Honoraria, Speakers Bureau; Loxo: Current equity holder in publicly-traded company; Seattle Genetics: Research Funding.

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 &lt;= 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.

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