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  • Online Resource  (5)
  • American Society of Hematology  (5)
  • Sui, Weiwei  (5)
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  • 1
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 47-48
    Abstract: Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 26-27
    Abstract: Background: Age is a pivotal prognostic factor for multiple myeloma (MM). The risk of evolving from MGUS and SMM to symptomatic MM steadily increases with age. And there are nuances in clinical manifestations and cytogenetic characteristics between young and old patients. The aim of this study is to delineate the clinical and laboratory features and determine the relative contribution of ISS, performance status and cytogenetic abnormalities in each age MM patients. Methods: In this study, 778 MM patients were enrolled in the prospective, non-randomized BDH2008/02 clinical trial between January, 2008 and December, 2016. Briefly, the patients accepted bortezomib or thalidomide-based induction therapy. Transplantation eligible patients accepted ASCT, otherwise they accepted the original regimen consolidation therapy. Subsequently, unless intolerance, patients received either thalidomide-based or lenalidomide-based maintenance therapy for two years. Conventional FISH panel included del(13q), del(17p), gain(1q), t(11;14), t(4;14), t(14;16), and t(14;20). The positive cut-off value for chromosome deletion or gain was 20%, and for chromosome translocation was 10%. A multivariate Cox proportional-hazards model was developed to assess the variables with significant effects on PFS and OS. Explained variation of variables was quantified by RD2. Statistical analysis was conducted by Stata/MP 16.0 (Stata Corp., TX, USA) and SPSS 26.0 (IBM Corp., Chicago, Illinois, USA). Results: Among 778 patients with complete data, 59.5% (463/778) were younger than 60 years old, 31.4% (244/778) were 61-70 years old, and only 9.1% (71/778) were over 71 years old. The median PFS of patients≤60, 61-70 and ≥71 years of age was 36.3, 32.6 and 23.1 months, respectively (P & lt;0.001). The median OS in each age group was 86.2, 60.7 and 34.9 months, respectively (P & lt;0.001) (Figure A-D). The median evaluated glomerular filtration rate of the three groups was 89.1, 74.0 and 66.4 ml/min (P & lt;0.001), respectively. The serum β2-microglobulin level gradually increased with age (P & lt;0.001), along with the proportion of patients with ISS 3 stage. Patients ≥71 years old had a higher proportion of ECOG performance status score 3-4, twice than that of patients ≤60 years old. The incidence of high-risk IgH translocation decreased with age, and was 25.4%, 21.3% and 14.3% across age groups. The incidence of gain(1q) increased with age, and was 43.9%, 47.1% and 54.8%, respectively. The incidence of del(17p) and del(13q) seldom changed with age (Figure E). With age, the risk of high-risk cytogenetic abnormalities did not change significantly, accounting for about 50% in each age group. The risk of ISS gradually decreased, accounting for 36%, 27%, and 14% in ≤60, 61-70 and ≥71 year subgroups, respectively. The risk of the ECOG performance status gradually increased with age, accounting for 10%, 17%, and 36% in the three subgroups (Figure F). The overall response rate of induction treatment gradually decreased with age, and were 90.2%, 81.9%, and 69.2%, respectively (P & lt;0.001). Elderly patients with impaired renal function or more than one high-risk cytogenetic abnormalities might benefit more from bortezomib based treatment than younger patients (Figure G). Conclusion: Age is an important prognostic factor in MM. With age, the risk of MM progression or death steadily grows. Cytogenetic abnormalities are equally important in every age group. The risk of poor performance status increases in elderly patients with a reduction risk in ISS. Elderly patients should focus on the status of frailty and molecular events to determine treatment. Figure Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5836-5836
    Abstract: Objective: To evaluate the efficacy and long-term outcome of the total treatment of induction therapy, ASCT and consolidation and maintenance therapy. Methods: A retrospective analysis was made on in multiple myeloma patients in our center between April 1, 2003 and February 1, 2016. The 157 patietns received autologous hematopoietic stem cell transplantation and review the autologous transplantation of long-term follow-up results. Analysis of the effect of transplantation efficacy, the impact on survival remission of different transplantation depth, transplantation in first line or not, salvage transplantation, prognosis of different staging system and other factors. Results: The baseline characteristics of the patients were shown in table 1. Overall patient ASCT before total effective rate (ORR) was 93.6%, in which the complete remission (CR) ratio was 33.1%. After ASCT, the best treatment response rate of PR was 80.3%, and the rate of CR was 58.6%. 91.69 months of median follow-up, patients with an overall survival (OS) and progression free survival (PFS) respectively 91.69 and 50.76 months; in 2005 before the median OS and PFS 39.0m and 23.0m. In 2005 after respectively and 56.41m 120.90m, P = 0.000. The median OS and PFS in the first line transplantation group and salvage transplantation group were vs 54.21m 39.0m and vs 7.09m 119.0m (P value was 0). 136 cases of patients with R-ISS stage, I, II, III of the patients with the median survival time were 120.90m (n=46), 86.43m (n=69), 35.65m (n=21), there were significant differences between groups, p=0.000. Each period of PFS were 72.11m, 51.84m, 28.09m, I and II, III,, p=0.001 and p=0.03, while there was no significant difference between II and III, p=0.122. The received autologous transplantation as first-line and salvage treatment of patients with subgroup survival analysis, median OS of the R-ISS stage III patients and different 15.84m 35.65m, P = 0.031; two groups of patients the median PFS (phase I: 91.69m vs18.92m; II: vs 16.69m 53.42m; phase III: vs 5.91m 28.52m) have difference (P = 0.000). In the first-line transplantation group, transplantation is more than or equal to PR and did not get effective PR group between OS were significantly different; before transplantation achieved CR, PR but did not obtain Cr and did not get effective PR group between PFS were significantly different; after transplantation and achieved CR CR did not get the patients had a median PFS were 65.57m 48.13m, P = 0.039 and median OS no difference. Accept any kind of noval agent- based chemotherapy were significantly longer OS and PFS than traditional chemotherapy (P = 0.001, P = 0.004) .There was no obvious difference on median OS between based regimen (bortezomib group median OS: NR; thalidomide group:120.90m); PFS in thalidomide group (median PFS : NR vs 54.21m) significantly prolonged (P = 0.010). By comparing the baseline characteristics of the two groups, it was found that the PFS was significantly shorter in the bortezomib group with an extra medullary lesion. Multivariate analysis showed that only R-ISS and the depth of remission before transplantation had effect on OS (p=0.003) and PFS (p=0.036) respectively. Conclusion: The total treatment of novel agent-based chemotherapy and ASCT for transplantation-eligible multiple myeloma patients is effective, further improve the remission rate and remission depth, prolong PFS and OS, the overall median survival up to 120.9m. First line transplantation can significantly prolong the OS and PFS compared with salvage transplantation. R-ISS and pre-transplant remission depth are prognostic factors influencing survival of patients. The total treatment to thalidomide based without extramedullary perhaps makes patients get long-term survival. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10585-10586
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5581-5581
    Abstract: OBJECTIVE:To review the role of ixazomib in the treatment of MM from a single center in China, focusing on the efficacy and safety of this oral PI at all stages of disease since ixazomib was approved by CFDA in 2018.METHODS:The data of real-world outcomes were collected from of the patients with high-risk multiple myeloma diagnosed in the blood diseases hospital,CAMS & PUMC from July 2018 to June 2019 when the patients received the first Ixazomib cycle. The patients were divided into three groups, which were salvage therapy of R/RMM, maintenance and frontline therapy of NDMM respectively.RESULTS:The first group was Ixa-based salvage treatment in R/RMM.31 patients were included and median age was 62years(47-71).The proportion of patients with cytogenetic high risk was 50%(One patient was unable to stratify risk). Extramedullary invasion was very high 40% in early relapse. Half of them received more than 2 lines of treatment, and about 10% received 4 or more lines of prior treatment. ORR was 51.6%; ≥ PR 35.5%; VGPR+CR9.7%.The median ixazomib therapy cycles were 3(1-12). 5 patients entered maintenance therapy for more than eight cycles.In all 8 patients who interruptedIxazomib treatment,six were due to disease progression,one was SD,and the remaining one will receive CART therapy.The median follow-up was 6.8 months, and the median PFS was not yet achieved.The survival curves of high-risk group and standard-risk group were obviously separated, but there was no statistical difference.However, the prognosis of extramedullary invasion group was very poor. PFS was significantly shorter than that of control group after treatment with Ixazomib(2.86m vs NA).The second group was Ixa-based maintenance therapy of NDMM. Seven patients received maintenance therapy after ASCT, and 20 transplant-ineligible(TIE) patients entered maintenance therapy.Maitenance with Ixazomib appears to have efficacy with deepen responses,the transplantation group(57.1%CR before vs 85.7%after) similar to the non-transplantation group(35.3%before vs 58.8%after).All the patients did not interrupt Ixazomib treatment.Only 1 patient(3.7%) had grade 4 adverse events, which was thrombocytopenia.The median ixazomib therapy cycles were 4(1-11).The third group was Ixa-based frontline therapy. The median age of 24 patients was 66y (42-79), CA High Risk was 25% (6/24), R-ISS III Stage was 12.5%(3/24), and no patients with EMD.The total of 9 patients were suitable for transplantation. Among them, 5 patients completed stem cell collection, 3 patients completed autotransplantation, 1 patient waited for transplantation, and 1 patient entered the continuous treatment group because of poor mobilization.The other 4 patients were still in induction stage. There were 15 patients in the TIE group and one patient dropped out of the group because of disease progression.The remaining 23 patients achieved a overall response rate of 78.3%. Nearly half of the patients achieved deep remission(VGPR+CR 43.5%).Posttransplantation patients could achieve 100% deep remission rate.As the number of treatment cycles increased, the proportion of complete remission increased in TIE patients.CONCLUSION:Ixazomib as induction/consolidation after ASCT, followed by maintenance, is well tolerated, convenient, and effective. Ixazomib is an important option for high-risk patients with real-world experience.KEYWORDS:Real-world, Ixazomib, multiple myeloma Figure Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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