Front-line daratumumab-VTd versus standard-of-care in ASCT-eligible multiple myeloma: matching-adjusted indirect comparison

Immunotherapy ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 143-154
Author(s):  
Philippe Moreau ◽  
Benjamin Hebraud ◽  
Thierry Facon ◽  
Xavier Leleu ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Indirect Comparison ◽  
Standard Of Care ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Front Line ◽  
Adjusted Indirect Comparison ◽  
Matching Adjustment

Aim: To compare daratumumab plus standard-of-care (SoC; bortezomib/thalidomide/dexamethasone [VTd]) and VTd alone with other SoC for transplant-eligible newly diagnosed multiple myeloma. Patients & methods: We conducted an unanchored matching-adjusted indirect comparison of progression-free and overall survival (PFS/OS) with D-VTd/VTd versus bortezomib/lenalidomide/dexamethasone (VRd), bortezomib/cyclophosphamide/dexamethasone (VCd) and bortezomib/dexamethasone (Vd). Results: After matching adjustment, significant improvements in PFS were estimated for D-VTd versus VRd (hazard ratio [HR]: 0.47 [95% CI: 0.33–0.69]), VCd (HR: 0.35 [95% CI: 0.21–0.58]) and Vd (HR: 0.42 [95% CI: 0.28–0.63]). OS was significantly longer with D-VTd versus VRd (HR: 0.31 [95% CI: 0.16–0.57]), VCd (HR: 0.35 [95% CI: 0.14–0.86]) and Vd (HR: 0.38 [95% CI: 0.18–0.77]). No significant PFS/OS differences were seen for VTd versus other SoC. Conclusion: This analysis supports front-line daratumumab for transplant-eligible newly diagnosed multiple myeloma.

scholarly journals Development of a Medicare Health Outcomes Survey Deficit-Accumulation Frailty Index and Its Application to Older Patients With Newly Diagnosed Multiple Myeloma

2018 ◽  
pp. 1-13 ◽  
Author(s):  
Hira S. Mian ◽  
Tanya M. Wildes ◽  
Mark A. Fiala
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Standard Deviation ◽  
Health Outcomes ◽  
Older Patients ◽  
Frailty Index ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Increased Risk ◽  
The Mean

Purpose To develop a frailty index using the Rockwood Accumulation of Deficits approach for the Medicare Health Outcomes Survey (MHOS) and apply it in a subset of older patients with newly diagnosed multiple myeloma. Methods Data from 2,692,361 patients without cancer, > 66 years of age, in SEER-MHOS linked databases between 1998 and 2009 were analyzed. A frailty index was constructed, resulting in a 25-item scale; cutoff values were created for individuals classified as frail. This frailty index was then applied to 305 patients with newly diagnosed myeloma in the database to predict overall survival. Results In the derivation cohort of patients without cancer, the median age was 74 years and the mean frailty index was 0.23 (standard deviation, 0.17). Among patients without cancer, each 10% increase in frailty index (approximately three to four more deficits) was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; 95% CI, 1.396 to 1.399; P < .001). In the cohort of patients with newly diagnosed myeloma, the median age was 76 years and the mean frailty index was 0.28 (standard deviation, 0.17). Each 10% increase in frailty index was associated with a 16% increased risk for death (adjusted hazard ratio, 1.159; 95% CI, 1.080 to 1.244; P < .001). Fifty-three percent of patients with multiple myeloma were considered frail. The estimated median overall survival of patients considered frail was 26.8 months, compared with 43.7 months ( P = .015) for those who were not. Conclusion The MHOS-based frailty index was prognostic for patients with multiple myeloma in predicting overall survival.

Tisagenlecleucel versus historical standard therapies for pediatric relapsed/refractory acute lymphoblastic leukemia

2020 ◽  
Vol 9 (12) ◽  
pp. 849-860
Author(s):  
Qiufei Ma ◽  
Jie Zhang ◽  
Elliott O'Brien ◽  
Amber L Martin ◽  
Andrea Chassot Agostinho
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Survival Benefit ◽  
Lymphoblastic Leukemia ◽  
Indirect Comparison ◽  
Standard Of Care ◽  
Salvage Chemotherapy ◽  
Adjusted Indirect Comparison ◽  
Baseline Characteristics ◽  
Combination Regimens

Aim: We compared outcomes from a single-arm study of tisagenlecleucel with standard of care (SOC) regimens in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Methods: The analysis included one tisagenlecleucel study, one blinatumomab study, one clofarabine monotherapy study, three studies of clofarabine combination regimens and two studies of other salvage chemotherapy. Matching-adjusted indirect comparison analyses were conducted. Results: After adjusting for baseline characteristics, tisagenlecleucel was associated with significantly prolonged overall survival compared with blinatumomab (hazard ratio [95% CI], 0.32 [0.16–0.64]); clofarabine monotherapy (0.24 [0.13–0.42]); clofarabine combination regimens (0.26 [0.15–0.45]); two salvage therapies (0.15 [0.09–0.25] and 0.27 [0.15–0.49]). Conclusion: The analysis demonstrated tisagenlecleucel was associated with substantially greater survival benefit versus all SOC regimens.

The effects of different schedules of bortezomib, melphalan, and prednisone for patients with newly diagnosed multiple myeloma who are transplant ineligible: a matching-adjusted indirect comparison

2019 ◽  
Vol 61 (3) ◽  
pp. 680-690 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Jesus San-Miguel ◽  
Hartmut Goldschmidt ◽  
Pieter Sonneveld ◽  
Meletios A. Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Indirect Comparison ◽  
Newly Diagnosed ◽  
Adjusted Indirect Comparison

The Bone Resorption Marker Serum-ICTP and the Circulating Proteasome Levels Separate ISS-Stages 1–3 and Are the Most Powerful Prognostic Factors for Overall Survival in Newly Diagnosed Symptomatic Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1475-1475
Author(s):  
Christian Jakob ◽  
Peter Liebisch ◽  
Karl Egerer ◽  
Jan Sterz ◽  
Martin Kaiser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Resorption ◽  
Hazard Ratio ◽  
Bone Resorption Marker ◽  
Type I ◽  
Newly Diagnosed ◽  
Normal Value ◽  
Cox Regression Analysis

Abstract Prognostic markers are important to identify high-risk patients in Multiple Myeloma (MM). Several prognostic models have been published, including parameters of tumor burden and cytogenetics. Recently the International Staging System (ISS) for Multiple Myeloma, which includes beta2-microglobulin (beta2-MG) and albumin, has been introduced for newly diagnosed patients with symptomatic MM. We previously reported about the prognostic significance of circulating proteasome levels (cProteasomes) in MM patients (Jakob et al., Blood 2007). In the present study we investigated the prognostic relevance of the bone resorption marker carboxy-terminal telopeptide of type-I collagen (ICTP) and cProteasome levels in comparison to the classical prognostic factors (beta2-MG), albumin, deletion 13q14 and type of chemotherapy (high-dose-therapy versus conventional dose chemotherapy) in 92 patients with newly diagnosed active MM. ICTP and cProteasome were significantly elevated parallel to ISS stages (P&lt;0.001). ICTP (cut off: normal value), cProteasome levels (cut off: median value) and a combined ICTP-cProteasome score (1: ICTP &lt; normal value and cProteasome &lt; median; 2: one of both parameters elevated; 3: both parameters elevated) were significant univariate prognostic factors for overall survival in active MM (P&lt;0.001, P=0.002 and P&lt;0.001, respectively). Survival rates at 5-yrs were 95%, 66% and 27% in the groups of patients with ICTP-cProteasome score 1, 2 and 3, respectively. In a further analysis ICTP alone and the combined ICTP-cProteasome score significantly separated each of the three ISS stages into two distinct groups with a better versus worse prognosis. In a multivariate Cox regression analysis, including beta2-MG, albumin, deletion 13q14, type of chemotherapy, cProteasome levels and ICTP, ICTP was the parameter with the strongest prognostic power (P&lt;0.001, hazard-ratio: 7.9) and cProteasomes (P=0.011, hazard-ratio: 3). Our study underlines that the activity of myeloma bone disease, as reflected by the collagen-I degradation product ICTP, has a major impact on the prognosis of symptomatic MM. This result is in line with published data showing a positive feedback between myeloma cells and osteoclasts, i.e. a vicious cycle. The inclusion of the bone resorption marker ICTP and cProteasome levels into multivariate models add substantial prognostic information on overall survival in newly diagnosed active MM.

scholarly journals Comparative survival analysis using the International Stratification Score (ISS) in newly-diagnosed multiple myeloma in the Uruguayan population

2021 ◽  
Author(s):  
David Israel Garrido ◽  
Virginia Bove ◽  
Victoria Matosas ◽  
Eloisa Riva
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Survival Analysis ◽  
Hematologic Malignancy ◽  
Staging System ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Survival Estimation ◽  
Real Practice

Background and aims. Multiple myeloma is a frequent hematologic malignancy, in which the International Stratification Score (ISS) is widely used to estimate the overall survival. However, there are no studies in Latin America evaluating its performance. This study aims to describe the ISS performance in the overall survival estimation for newly diagnosed multiple myeloma patients in Uruguay. Methods. This is a retrospective registry‐based survival analysis through the Grupo Uruguayo de Mieloma Múltiple (GUMMA) database, including newly diagnosed multiple myeloma patients from January 2001 until May 2019. Results. 249 patients were included, 51.81% males and an average age of 63.49 years. According to ISS and Durie-Salmon score (DSS), 47.79% and 82.3% were ISS III and DSS III, respectively. Also, 32.3% were DSS B. Auto hematopoietic stem cell transplantation was performed in 31.73% of patients, and bortezomib was used in 44.18% as frontline therapy. The overall survival was 80% for ISS1, 64.9% ISS2, and 48.6% ISS3 (Log-Rank; p <0.01). The average overall survival was 116.5 months for ISS 1, 77.6 months for ISS 2, and 57.8 months for ISS 3. The hazard ratio between ISS II and ISS I was 2.42 (95% CI 1.10-5.33; p<0.05), and 3.94 (95% CI 1.88-8.26; p<0.05) between ISS III and ISS II. Conclusion. The ISS staging system allows an adequate stratification of patients according to overall survival in the real-practice setting. However, considering the relevance of the new cytogenetic advances, it is necessary to increase the availability and quality of iFISH in Latin America.

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