-
1.
Prognostic nomogram for multiple myeloma early relapse after autologous stem cell transplant in the novel agent era
Zhou, H., Jian, Y., Du, J., Liu, J., Zhang, Z., Yang, G., Wang, G., Tian, Y., Li, Y., Wu, Y., et al
Cancer medicine. 2023
Abstract
BACKGROUND The present study intended to establish a predictive nomogram for early relapse (ER) (<12 months) after autologous stem cell transplantation (ASCT) in the novel drug era for multiple myeloma (MM). PATIENTS AND METHODS The nomogram was designed and constructed to a retrospective clinical data of newly diagnosed MM patients received novel agent induction therapy and subsequent ASCT at three centers in China from July 2007 to December 2018. The retrospective study was conducted among 294 patients in the training cohort and 126 in the validation cohort. The nomogram's predictive accuracy was evaluated by the concordance index, calibration curve and decision clinical curve. RESULTS The study cohort included 420 newly diagnosed MM patients, and 100 (23.8%) were identified as having ER, including 74 in the training cohort and 26 in the validation cohort. According to the result of multivariate regression in the training cohort, the prognostic variables included in the nomogram were high-risk cytogenetics, LDH > UNL, and response less than very good partial response (VGPR) after ASCT. The calibration curve showed good fitness between the nomogram predictions and the actual observations and the nomogram was further validated by a clinical decision curve. The nomogram's C-index achieved 0.75 (95% CI, 0.70-0.80), which was higher than that of the Revised International Staging System (R-ISS) (0.62), ISS (0.59), and Durie-Salmon (DS) staging system (0.52). The discrimination ability of the nomogram in the validation cohort was superior to that of the other staging systems (C-index: 0.73 vs. R-ISS (0.54), ISS (0.55), and DS staging system (0.53)). DCA showed the prediction nomogram adds much more clinical utility. Different scores of the nomogram draw a distinction of OS. CONCLUSION The present nomogram could serve as a feasible and accurate prediction of ER in novel drug induction transplantation-eligible MM patients, which could help modify the post-ASCT strategy for patients at high risk of ER.
-
2.
Risk factors, treatments and outcomes of patients with light chain amyloidosis who relapse after autologous stem cell transplantation
Zhang, Y., Guo, J., Chen, W., Zhao, L., Huang, X.
Bone marrow transplantation. 2023
Abstract
Relapse after ASCT is an important factor affecting the long-term prognosis of patients with AL amyloidosis. However, the risk factors of relapse are unknown and there are limited studies on treatment outcomes of these patients. We retrospectively reviewed 170 patients with AL amyloidosis who underwent ASCT between 2010 and 2021. Seventy-six patients confirmed as relapse and the median time from ASCT to relapse was 39 months. On multivariate analysis of variables before and after ASCT, lambda restricted, dFLC >30 mg/L pre ASCT, reduced dose melphalan and dFLC >10 mg/L at 6 months after ASCT were independent risk factors for relapse, and achieving CR after induction therapy and renal response after ASCT were protective factors. Most relapsed patients were treated with bortezomib-based regimens (50%) followed by daratumumab-based regimens (22.2%) and other chemotherapy regimens (13.9%). The overall hematological response in evaluable patients was 68.2% with 56.8% achieving CR/VGPR. The median PFS and OS from post-transplant relapse were 25 months and 81 months, respectively. Patients receiving bortezomib or daratumumab showed a better survival compared to other chemotherapy regimens. In conclusion, this study identified independent risk factors of post-transplant relapse and demonstrated the superiority of bortezomib or daratumumab treatment for these patients. CLINICAL TRIAL REGISTRATION NCT04210791.
-
3.
Triplet RVd Induction for Transplant-Eligible Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis
Yang, G., Geng, C., Jian, Y., Zhou, H., Chen, W.
Advances in therapy. 2022
Abstract
INTRODUCTION The combination of lenalidomide, bortezomib, and dexamethasone (RVd) has become standard of care for transplant-eligible patients with newly diagnosed MM (NDMM). This study aimed to determine the efficacy of RVd as induction therapy in terms of response rates and survival outcomes of transplant-eligible patients with NDMM. METHODS The databases of Medline, Embase, and Cochrane Library were searched until February 1, 2021. Both randomized controlled trials (RCT) and non-RCTs from the available literature were extracted as one-arm data to assess the efficacy of each triplet regimen for the target patients in terms of response rates and survival rates for transplant-eligible patients with NDMM. Data was summarized as estimated pooled value regarding each evaluated index. Risk of bias of studies was assessed with standard methods. RESULTS The findings of 71 studies published from 2008 to 2020 were analyzed. For RVd induction, the overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate after induction were 0.91 (95% CI 0.86-0.95), 0.23 (95% CI 0.17-0.29), and 0.56 (95% CI 0.51-0.61), respectively. Indirect comparisons in efficacy were made between RVd and other traditional triplet regimens. RVd induction led to a better ≥ CR rate than bortezomib, cyclophosphamide, and dexamethasone (VCd) regimen in both postinduction and post-ASCT phase, ≥ CR rate 0.11 (95% CI 0.08-0.15) and 0.21 (95% CI 0.12-0.32), respectively. The 1-year overall survival (OS) rate and 3-year OS rate of RVd regimen were longer than that of bortezomib, thalidomide, and dexamethasone (VTd), 0.97 (95% CI 0.94-0.98) vs 0.71 (95% CI 0.61-0.80), and 0.90 (95% CI 0.79-0.98) vs 0.70 (95% CI 0.64-0.75), respectively. CONCLUSIONS The RVd induction demonstrated confident response rates and survival benefits for transplant-eligible patients with NDMM.
-
4.
What Multiple Myeloma With t(11;14) Should Be Classified Into in Novel Agent Era: Standard or Intermediate Risk?
Gao, W., Du, J., Liu, J., Zhou, H., Zhang, Z., Jian, Y., Yang, G., Wang, G., Tian, Y., Li, Y., et al
Frontiers in oncology. 2020;10:538126
Abstract
OBJECTIVE To investigate the prognostic value of t(11;14) for de novo multiple myeloma (MM) patients in novel agent era. METHODS A total of 455 patients with fluorescence in situ hybridization (FISH), before treatments from three hospitals in China, were included in the study. All patients received autologous stem cell transplantation (ASCT) after induction therapy as consolidation. High risk (HR) cytogenetics were defined as t(4;14), t(14;16), and/or del 17p. RESULTS A total of 152 patients were in the HR group. Of patients without HR cytogenetics, 55 were in the t(11;14) group, and 248 were in the standard risk (SR) group without t(11;14). Gain in 1q21 was observed in 38.9% patients with t(11;14). There were no differences in median progression free survival (PFS) and overall survival (OS), respectively, between patients in the t(11;14) group and those in the SR group. Patients in the t(11;14) group had the longer median PFS and OS, respectively, compared with those in the HR group. Regardless of coexisting with 1q21 gain or not, patients in the t(11;14) group still had similar median PFS and OS compared to those in the SR group. Finally, multivariate analysis indicated that including 1q21 gain and bone marrow plasma cell with CD20 expression, no variables were found to predict the outcome of the t(11;14) group in our cohort. CONCLUSIONS These results confirm that outcomes of t(11;14) MM are similar to standard risk patients when they receive novel agent induction therapy consolidated by ASCT. Gain of 1q21 coexists with t(11;14) frequently. In addition, both bone marrow plasma cell with CD20 expression and 1q21 gain have no impact on median PFS or OS for patients with t(11;14).
-
5.
Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China
Gao, W., Jian, Y., Du, J., Li, X., Zhou, H., Zhang, Z., Yang, G., Wang, G., Tian, Y., Li, Y., et al
Cancer medicine. 2020;9(21):7819-7829
Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) has been recommended as a standard approach for young multiple myeloma (MM) patients for decades, even in the era of novel agents. Gain of chromosome 1q21 is a common cytogenetic abnormality in MM, while its clinical prognostic value is still controversial. METHODS In this multicenter study, we retrospectively analyzed 1q21 gain in 446 newly diagnosed MM patients who received at least one ASCT from three large myeloma centers in China. RESULTS Of the all 446 patients, 1q21 gain was an adverse predictor of progression-free survival (PFS) (34 vs 56 months, P = .005) and overall survival (OS) (69 vs 100 months, P = .002). Gain of 1q21 was more likely to coexist with t(4;14), t(14;16), and del(13q). Nevertheless, isolated 1q21 gain still exhibited unfavorable effects on PFS (35 vs 66 months, P = .045) and OS (61 vs 100 months, P = .026). The coexistence of 1q21 gain and high-risk cytogenetics (HRCs) [del(17p), t(4;14),and/or t(14;16)] showed poor prognosis on both PFS and OS, while no additional adverse effect could be identified when compared with HRCs alone. Moreover, when coexisting with t(11;14), patients with 1q21 gain showed a comparable survival to those without 1q21 gain. For patients treated with novel induction regimens followed by ASCT, 1q21 gain also conferred an inferior prognosis. Multivariate analysis further confirmed 1q21 gain could independently predict shorter PFS and OS. CONCLUSION In conclusion, 1q21 gain is an adverse prognostic factor for MM patients received ASCT.
-
6.
The role of induction therapy before autologous stem cell transplantation in low disease burden AL amyloidosis patients
Huang, X., Ren, G., Chen, W., Guo, J., Zhao, L., Zeng, C., Ge, Y., Liu, Z.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2020;:1-9
Abstract
BACKGROUND Induction therapy is recommended before autologous stem cell transplantation (ASCT) for AL amyloidosis patients with high disease burden [bone marrow plasma cells (BMPCs) > 10%], but the role of induction therapy before ASCT in patients with low disease burden (BMPCs ≤ 10%) is still unknown. METHODS A total of 227 patients with AL amyloidosis were included in this study. Among 227 patients, 124 patients received bortezomib-based induction prior to ASCT and were defined as group A, 35 patients received other chemotherapeutic induction and were defined as group B, and the other 68 patients without induction were defined as group C. We compared the differences of efficacy and prognosis between the three groups. RESULTS The haematological overall response rates (ORR) of groups A, B and C were 91%, 67% and 75%, respectively. The complete response rates (CR) of groups A, B and C were 50%, 25% and 20%, respectively. Both the ORR and CR rates of group A were significantly higher than those of groups B and C. The renal response rates of groups A, B and C were 64%, 46% and 47%, respectively. The cardiac response rates of groups A, B and C were 74%, 45% and 40%, respectively. The renal and cardiac responses rates of group A were also significantly higher than those of the other two groups. After a median follow-up of 44 months, the median OS was not reached. The 5-year estimated overall survival (OS) rates of groups A, B and C were 81%, 57% and 67%, respectively. The median progression-free survival (PFS) was 83 months for all patients. The 5-year estimated PFS rates of groups A, B and C were 61%, 38% and 49%, respectively. Both the OS and PFS of group A were higher than those of both group B and group C. On multivariate analysis, baseline dFLC > 50 mg/L was associated with worse survival, but induction with bortezomib was associated with better survival. CONCLUSION Our study demonstrated that low disease burden AL patients who are eligible for ASCT may benefit from bortezomib-based induction therapy.
-
7.
Immunoparesis recovery 1 year after ASCT is independently associated with favorable survival in patients with symptomatic multiple myeloma who undergo autologous stem cell transplantation
Gao, W., Li, J., Wu, Y., Li, Y., Leng, Y., Liu, A., Yang, G., Tian, Y., Wang, H., Wang, G., et al
Annals of hematology. 2019
Abstract
Immunoparesis is defined as a reduction in the levels of one, two, or three uninvolved immunoglobulins. However, there are very limited data on the incidence and prognostic significance of immunoparesis recovery 1 year after autologous stem cell transplantation (ASCT) in MM. We reviewed medical records of de novo MM patients who received ASCT at Beijing Chao Yang hospital. One hundred eight MM patients were included in the study. Conventional chemotherapy was administered as induction regimen in 16 patients (14.8%), whereas novel agents were used in 92 patients (85.2%). Most patients had immunoparesis at diagnosis (89.1%) and at the moment of ASCT as well (75%). After a median follow-up of 49 months, in the group with immunoglobulin recovery 1 year after ASCT, there was a trend towards longer progression-free survival (PFS) than in the group with immunoparesis (P = 0.054). And overall survival (OS) was significantly longer in patients with immunoparesis recovery (P = 0.004). In multivariate analysis, immunoparesis recovery 1 year after ASCT was independently associated with improved OS (P = 0.016). In conclusion, lack of immunoparesis recovery 1 year after ASCT in MM patients is associated with significantly shorter OS and this group of patients needs new treatment strategy to improve the prognosis.
-
8.
1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China
Li, X., Chen, W., Li, J., Chen, L., Fang, B., Feng, Y., Liu, J., Chen, M., Gu, J., Huang, B., et al
The oncologist. 2019
Abstract
BACKGROUND The prognostic value of 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Our aim was to investigate the prognostic value of 1q21 gain in a Chinese population. MATERIALS AND METHODS We retrospectively identified 565 patients with NDMM from multiple centers in China. RESULTS We detected 1q21 gain in 222 (39.3%) patients, among whom 144 had three copies of 1q21, 57 had four copies of 1q21, and 21 had at least five copies of 1q21. Copy number variation did not show any effect on the disease outcome. Multivariate analysis indicated that 1q21 gain was an independent factor for poor prognosis, but we found that 1q21 gain was strongly associated with other high-risk factors, such as del(17p), t(4;14), t(14;16), lactate dehydrogenase (LDH) level >300 U/L and International Scoring System (ISS) stage II-III (p < .001). Further analysis revealed that in the absence of other high-risk factors, isolated 1q21 gain resulted in similar progression-free survival (PFS; 52.0 vs. 52.8 months, p = .810) and overall survival (OS; not reached vs. not reached, p = .833); additionally, when present with other high-risk cytogenetic abnormalities or increased LDH levels, 1q21 gain lost its prognostic power. However, the presence of 1q21 gain increased the adverse impact of ISS stage. Furthermore, 1q21 gain predicted poor PFS and OS in patients who received bortezomib-based regimens. Moreover, autologous stem cell transplantation reversed the poor prognosis in patients with 1q21 gain. CONCLUSION Our results show that heterogeneity exists among patients with 1q21 gain and suggest that we should assess the impact of 1q21 gain on prognosis according to different treatment regimens and accompanying high-risk factors. IMPLICATIONS FOR PRACTICE 1q21 gain is one of the most common chromosomal aberrations in multiple myeloma (MM); however, the prognostic value of 1q21 gain remains controversial. This study investigated the prognostic value of 1q21 gain in a Chinese population with newly diagnosed MM. The results showed that heterogeneity exists among patients with 1q21 gain and suggested that the impact of 1q21 gain on prognosis should be assessed according to different treatment regimens and accompanying high-risk factors. These results could help stratify risk in patients with MM and guide treatment decisions.
-
9.
Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis
Huang, X., Chen, W., Ren, G., Zhao, L., Guo, J., Gong, D., Zeng, C., Hu, W., Liu, Z.
Clinical journal of the American Society of Nephrology : CJASN. 2019
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVES Our study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS From July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment. RESULTS Twenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33-71) months. The mean number of CD34(+) cells was (7.3+/-3.8)x10(6)/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7-9) and 9 (6-10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60-80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%. CONCLUSIONS Autologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.
-
10.
Combination of bortezomib in the induction, conditioning and consolidation with autologous hematopoietic stem cell transplantation in patients with immunoglobulin light chain amyloidosis
Huang, X., Fu, Z., Chen, L., Chen, W., Ren, G., Guo, J., Zhao, L., Zeng, C., Zhang, H., Gong, D., et al
American journal of hematology. 2019
Abstract
Bortezomib and autologous hematopoietic stem cell transplantation (ASCT) are both active regimen in AL amyloidosis. In this study, we assessed safety and efficacy of combination of bortezomib in the induction, conditioning and consolidation with ASCT in patients with newly diagnosed AL amyloidosis. Treatment schedule consisted of two cycles of bortezomib and dexamethasone (BD) induction therapy, ASCT treatment (the conditioning regimen consisted of melphalan and bortezomib), and four additional 21-day cycles of bortezomib treatment after ASCT. Twenty-one patients were enrolled in the study. Nine patients had cardiac involvement. The overall response rate (ORR) was 90% (18/20) at 12 months after ASCT in evaluable patients, including 10 patients (50%) with complete response, 7 patients (35%) with very good partial response. The organ response rate was 72.2%. The renal and cardiac response was 55% and 40% at 12 months after ASCT respectively, and reached to 66.7% and 50% at 24 months. Peripheral neuropathy and infection were the common adverse events during the treatment, and five patients have been discontinued bortezomib for neuropathy. No death occurred in this study. After a median follow-up of 53 months, the overall survival was 100%, and the estimated progression free survival was 79.9% at 60 months. Data from this study demonstrate that incorporating bortezomib into induction, conditioning and consolidation with ASCT yielded a high rate of hematologic response with tolerable toxicity in patients with AL amyloidosis. The overall survival and progression-free survival also improved after long term follow-up in these patients. (ClinicalTrial.gov Identifier: NCT01273844). This article is protected by copyright. All rights reserved.