Trends in pre- and post-transplant therapies with first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004-2014.
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ABSTRACT:
SUBMITTER: D'Souza A
PROVIDER: S-EPMC5587375 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Trends in pre- and post-transplant therapies with first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004-2014.
D'Souza A A Zhang M-J MJ Huang J J Fei M M Pasquini M M Hamadani M M Hari P P
Leukemia 20170613 9
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Project description:Autologous hematopoietic stem cell transplantation (AHCT) improves survival in patients with multiple myeloma (MM) but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and survival in patients with MM undergoing AHCT. We analyzed outcomes of 1156 patients of AHCT after high-dose melphalan reported to the Center for International Blood and Marrow Transplant Research. Individual comorbidities were prospectively collected at the time of AHCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subjects score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohort). One-year NRM was low at 2% (95% confidence interval, 1% to 4%) and did not correlate with HCT-CI score (P = .9). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Overall survival was also inferior with KPS < 90 (P < .001), IgA subtype (P ≤ .001), those receiving >1 pretransplant induction regimen (P = .007), and those with resistant disease at the time of AHCT (P < .001). AHCT for MM is associated with low NRM, and death is predominantly related to disease progression. Although a higher HCT-CI score did not predict NRM, it was associated with inferior survival.
| S-EPMC3961011 | biostudies-literature
Project description:BackgroundRace/ethnicity remains an important barrier in clinical care. The authors investigated differences in the receipt of autologous hematopoietic cell transplantation (AHCT) among patients with multiple myeloma (MM) and outcomes based on race/ethnicity in the United States.MethodsThe Center for International Blood and Marrow Transplant Research database was used to identify 28,450 patients who underwent AHCT for MM from 2008 through 2014. By using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registries, the incidence of MM was calculated, and a stem cell transplantation utilization rate (STUR) was derived. Post-AHCT outcomes were analyzed among patients ages 18 to 75 years who underwent melphalan-conditioned peripheral cell grafts (N = 24,102).ResultsThe STUR increased across all groups from 2008 to 2014. The increase was substantially lower among Hispanics (range, 8.6%-16.9%) and non-Hispanic blacks (range, 12.2%-20.5%) compared with non-Hispanic whites (range, 22.6%-37.8%). There were 18,046 non-Hispanic whites, 4123 non-Hispanic blacks, and 1933 Hispanic patients. The Hispanic group was younger (P < .001). Fewer patients older than 60 years underwent transplantation among Hispanics (39%) and non-Hispanic blacks (42%) compared with non-Hispanic whites (56%). A Karnofsky score <90% and a hematopoietic cell transplantation comorbidity index score >3 were more common in non-Hispanic blacks compared with Hispanic and non-Hispanic whites (P < .001). More Hispanics (57%) versus non-Hispanic blacks (54%) and non-Hispanic whites (52%; P < .001) had stage III disease. More Hispanics (48%) versus non-Hispanic blacks (45%) and non-Hispanic whites (44%) had a very good partial response or better before transplantation (P = .005). Race/ethnicity did not impact post-AHCT outcomes.ConclusionsAlthough the STUR increased, it remained low and was significantly lower among Hispanics followed by non-Hispanic blacks compared with non-Hispanic whites. Race/ethnicity did not impact transplantation outcomes. Efforts to increase the rates of transplantation for eligible patients who have MM, with an emphasis on groups that underuse transplantation, are warranted. Cancer 2017;123:3141-9. © 2017 American Cancer Society.
| S-EPMC5544566 | biostudies-literature
Project description:We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8.5 years. Relapse occurred before 6 months after a second HCT in 46% of the auto/allo patients, compared with 26% of the auto/auto patients. The 6-year postrelapse survival was better in the auto/allo group compared with the auto/auto group (44% versus 35%; P = .05). Mortality due to MM was 69% (n = 101) in the auto/allo group and 83% (n = 229) deaths in auto/auto group. In multivariate analysis, both cohorts had a similar risk of death in the first year after relapse (hazard ratio [HR], .72; P = .12); however, for time points beyond 12 months after relapse, overall survival was superior in the auto/allo cohort (HR for death in auto/auto =1.55; P = .005). Other factors associated with superior survival were enrollment in a clinical trial for HCT, male sex, and use of novel agents at induction before HCT. Our findings shown superior survival afterrelapse in auto/allo HCT recipients compared with auto/auto HCT recipients. This likely reflects a better response to salvage therapy, such as immunomodulatory drugs, potentiated by a donor-derived immunologic milieu. Further augmentation of the post-allo-HCT immune system with new immunotherapies, such as monoclonal antibodies, checkpoint inhibitors, and others, merit investigation.
| S-EPMC5826888 | biostudies-literature
Project description:Autologous hematopoietic cell transplantation (Auto-HCT) is commonly an in-patient procedure. However, Auto-HCT is increasingly being offered on an outpatient basis. To better characterize the safety of outpatient Auto-HCT, we compared the outcome of 230 patients who underwent Auto-HCT on an in-patient vs outpatient basis for myeloma or lymphoma within a single transplant program. All outpatient transplants occurred in a cancer center day hospital. Hematopoietic recovery occurred earlier in the outpatient cohort, with median time to neutrophil recovery of 10 vs 11 days (P<0.001) and median time to platelet recovery of 19 vs 20 days (P=0.053). Fifty-one percent of the outpatient cohort never required admission, with this percentage increasing in later years. Grade 3-4 non-hematologic toxicities occurred in 29% of both cohorts. Non-relapse mortality at 1 year was 0% in the outpatient cohort and 1.5% in the in-patient cohort (P=0.327). Two-year PFS was 62% for outpatient vs 54% for in-patient (P=0.155). One- and two-year OS was 97% and 83% for outpatient vs 91% and 80% for in-patient, respectively (P=0.271). We conclude that, with daily outpatient evaluation and aggressive supportive care, outpatient Auto-HCT can result in excellent outcomes for myeloma and lymphoma patients.
| S-EPMC4490016 | biostudies-literature
Project description:We studied 2,528 patients with upfront autologous haematopoietic cell transplantation (AHCT) for multiple myeloma (MM) from 2008-2017 to develop a prognostic model to predict outcomes. High-risk cytogenetics included t(4;14), t(14;16), t(14;20), del13q on karyotype, del17p, +1q or 1pdel. A Cox model identified factors prognostic of progression/relapse in a training subset (n = 1,246). A weighted score using these factors was assigned to a validation cohort (n = 774). Presence of high-risk cytogenetics [hazard ratio, (HR) 1·68 (1·3-2·17)] and pre-AHCT bone marrow plasma cells (BMPCs) ≥10% [1·68 (1·33-2·12)] were assigned 4 points each; albumin at diagnosis <3·5 g/dl [1·31 (1·07-1·61)] 2; standard risk cytogenetics 1, and no cytogenetics abnormality, BMPCs <10% at AHCT and albumin ≥3·5 g/dl at diagnosis 0 points each. A three-category system with low risk (0-3), intermediate risk (4-8) and high risk (9-10) showed 3-year progression-free survival in the low vs. intermediate vs. high risk of 58% (95% CI: 52-63) vs. 49% (95% CI: 43-56) vs. 31% (95% CI: 12-51), P < 0.001 respectively, and 3-year OS in low vs. intermediate vs. high risk of 88% (95% CI: 84-91) vs. 81% (95% CI: 76-86) vs. 64% (95% CI: 39-80); P < 0·001. Our prognostic scoring system can identify MM patients at risk for early relapse after AHCT.
| S-EPMC7990054 | biostudies-literature
Project description:We evaluated tandem autologous/allogeneic hematopoietic cell transplantation followed by bortezomib maintenance therapy in a prospective phase 2 trial of treatment of high-risk multiple myeloma. The high-dose conditioning regimen for autologous hematopoietic cell transplantation consisted of melphalan 200 mg/m2. The nonmyeloablative conditioning regimen for the allogeneic transplant involved low-dose total body irradiation (2 Gy) with or without fludarabine (30 mg/m2 × 3 days). Among the 31 patients enrolled, 26 (84%) proceeded to HLA-matched allogeneic hematopoietic cell transplantation at a median of 61 (range, 41-168) days following the autologous transplant. Twenty-one patients (68%) started bortezomib (1.6 mg/m2 IV or 2.6 mg/m2 subcutaneously every 14 days for 9 months) at a median of 79 (range, 63-103) days after allogeneic transplantation. With a median follow-up of 51 (range, 16-86) months and based on intention to treat, the 2-year and 4-year progression-free survival and overall survival estimates among 24 newly diagnosed high-risk patients were 71% and 75%, and 52% and 61%, respectively. The 7 patients enrolled with relapsed or persistent disease had a 2-year and 4-year progression-free survival and overall survival rates of 14% and 43%, and 14% and 29%, respectively. These findings suggest that for patients with newly diagnosed high-risk multiple myeloma, bortezomib maintenance therapy after tandem autologous/allogeneic hematopoietic cell transplantation is safe and may prevent disease progression until full establishment of a graft-versus-myeloma effect. This benefit, however, does not extend to patients who enroll after unsuccessful prior therapy. This trial was registered at www.clinicaltrials.gov as #NCT00793572.
| S-EPMC5737131 | biostudies-literature
Project description:The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p < 0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p < 0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p < 0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes.
| S-EPMC8764606 | biostudies-literature
Project description: Not available
| S-EPMC9278304 | biostudies-literature
Project description:We previously reported initial results in 102 multiple myeloma (MM) patients treated with sequential high-dose melphalan and autologous hematopoietic cell transplantation followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m2 and allogeneic hematopoietic cell transplantation. Here we present long-term clinical outcomes among the 102 initial patients and among 142 additional patients, with a median follow up of 8.3 (range 1.0-18.1) years. Donors included human leukocyte antigen identical siblings (n=179) and HLA-matched unrelated donors (n=65). A total of 209 patients (86%) received tandem autologous-allogeneic upfront, while thirty-five patients (14%) had failed a previous autologous hematopoietic cell transplantation before the planned autologous-allogeneic transplantation. Thirty-one patients received maintenance treatment at a median of 86 days (range, 61-150) after allogeneic transplantation. Five-year rates of overall survival (OS) and progression-free survival (PFS) were 54% and 31%, respectively. Ten-year OS and PFS were 41% and 19%, respectively. Overall non-relapse mortality was 2% at 100 days and 14% at five years. Patients with induction-refractory disease and those with high-risk biological features experienced shorter OS and PFS. A total of 152 patients experienced disease relapse and 117 of those received salvage treatment. Eighty-three of the 117 patients achieved a clinical response, and for those, the median duration of survival after relapse was 7.8 years. Moreover, a subset of patients who became negative for minimal residual disease (MRD) by flow cytometry experienced a significantly lower relapse rate as compared with MRD-positive patients (P=0.03). Our study showed that the graft-versus-myeloma effect after non-myeloablative allografting allowed long-term disease control in standard and high-risk patient subsets. Ultra-high-risk patients did not appear to benefit from tandem autologous/allogeneic hematopoietic cell transplantation because of early disease relapse. Incorporation of newer anti-MM agents into the initial induction treatments before tandem hematopoietic cell transplantation and during maintenance might improve outcomes of ultra-high-risk patients. Clinical trials included in this study are registered at: clinicaltrials.gov identifiers: 00075478, 00005799, 01251575, 00078858, 00105001, 00027820, 00089011, 00003196, 00006251, 00793572, 00054353, 00014235, 00003954.
| S-EPMC6355483 | biostudies-literature
Project description:Autologous stem cell transplant (ASCT) is an effective treatment for multiple myeloma (MM). However, the timing of ASCT in the era of novel agents (lenalidomide, thalidomide, bortezomib) is unknown. We retrospectively reviewed the outcome of patients with MM who received novel agent-based induction treatment and received first ASCT within 12 months of diagnosis (early ASCT, n = 102) or at a later date (late ASCT, n = 65). Median time to ASCT was 7.9 months vs. 17.7 months in early vs. late ASCT. The 3- and 5-year overall survival (OS) from diagnosis was 90 and 63% vs. 82 and 63% in early and late ASCT, respectively (p = 0.45). Forty-one and 36 patients in the early and late ASCT groups have relapsed or progressed, with median time to relapse of 28 and 23 months (p = 0.055). On multivariable analysis, factors predictive of increased risk for progression were International Scoring System (ISS) stage III (p = 0.007), and less than a very good partial response (< VGPR) post-ASCT (p < 0.001). A factor predictive of worst outcome for OS was being on hemodialysis (p = 0.037). No superiority of one agent was seen. In summary, early or late ASCT is a viable option for patients with MM receiving induction treatment with novel targeted therapies.
| S-EPMC3769940 | biostudies-literature