Efficacy of daratumumab + SOC versus SOC in myeloma induction regimens, by risk-stratification: Meta-analysis of phase III randomized control trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20512-e20512
Author(s):  
Nisha Joseph ◽  
Craig C. Hofmeister ◽  
Madhav V. Dhodapkar ◽  
Lawrence Boise ◽  
Sagar Lonial ◽  
...  
Keyword(s):  
High Risk ◽  
Meta Analysis ◽  
Phase 3 ◽  
High Risk Patients ◽  
Hazard Ratios ◽  
Risk Patients ◽  
Q Statistic ◽  
The Impact ◽  
Standard Risk

e20512 Background: Addition of daratumumab, a CD38 monoclonal antibody, to standard of care (SOC) myeloma induction regimens resulted in deeper responses. Phase 3 trials comparing daratumumab + SOC vs SOC consistently favored the daratumumab combinations. The objective of this analysis is to test the hypothesis that high-risk patients benefit from the addition of daratumumab to SOC induction regimens. Methods: We identified four phase 3 clinical trials (RCT) that randomized newly diagnosed myeloma patients to receive daratumumab +SOC vs. SOC. The GRIFFIN trial did not have PFS events and was excluded. A meta-analysis of 3 RCTs with updated data from ASH 2019 (ALCYONE, MAIA, CASSIOPEIA) was performed using the fixed (Mantel-Haenszel) model to calculate the impact of daratumumab + SOC versus SOC. The consistency of results (effect sizes) among studies was investigated by means of two heterogeneity tests, the χ 2-based Cochran's Q test, and the I2 Statistic. We considered that heterogeneity was present when the P value of the Cochran's Q test was < 0.1 and I2 statistic was > 50%. Results: The pooled hazard ratios (HR) for standard risk patients for PFS was HR 0.589 (95% CI 0.502-0.691; P < 0.001) in favor of daratumumab. Q-statistic for PFS ( P= 3.462; df= 2; I2 = 42.23) suggests homogeneity across studies. The pooled hazard ratios (HR) for high risk patients for PFS was HR 0.799 (95% CI 0.609-1.047; P= 0.104) in favor of daratumumab. Q-statistic for PFS ( P= 1.306; df= 2; I2 = 0.00) suggests homogeneity across studies. Conclusions: Our meta-analysis demonstrates that addition of daratumumab to SOC myeloma induction regimens prevented progression in both standard and high-risk patients, though the impact was more pronounced in the standard-risk patients. This benefit seems to improve with longer follow up, as seen both in ALCYONE (Mateos et al ASH 2019) and MAIA trial (Bahlis et al ASH 2019). Focused accrual of high-risk patients in larger daratumumab induction trials and longer follow up of the existing trials are further needed.

Survival in Patients with Newly Diagnosed Myeloma Undergoing Therapy with Lenalidomide and Dexamethasone: Impact of High-Risk Cytogenetic Risk Status on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 95-95 ◽  
Author(s):  
Prashant Kapoor ◽  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E Witzig ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Stratification ◽  
Plasma Cell ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact ◽  
Standard Risk

Abstract Background: Multiple myeloma (MM) is a heterogeneous disease with very divergent outcomes that are dictated in a large part by specific cytogenetic abnormalities, as well as other prognostic factors such as the proliferative rate of marrow plasma cells. Prognostic systems incorporating these factors have shown clinical utility in identifying high-risk patients, and are increasingly being utilized for treatment decision-making. However, the prognostic relevance of these factors may change with the application of novel therapies. The objective of this study was to determine the impact of risk-stratification (incorporating plasma cell metaphase cytogenetics, interphase fluorescent in-situ hybridization (FISH) and the slide-based plasma cell labeling index (PCLI)) in a cohort of patients with newly diagnosed MM treated initially with lenalidomide + dexamethasone (Rev-Dex). Methods: From March 2004 to November 2007, 100 consecutive patients treated with Rev (25mg/day) on days 1 through 21 of a 4-week cycle in combination with dexamethasone as initial therapy for newly diagnosed myeloma, were identified. High-risk MM was defined as presence of any one or more of the following: hypodiploidy, monoallelic loss of chromosome 13 or its long arm (by metaphase cytogenetics only), deletion of p53 (locus 17p13) or PCLI ≥ 3% or immunoglobulin heavy chain (IgH) translocations, t(4;14) (p16.3;q32) or t(14;16)(q32;q23) on FISH. PFS and OS survival estimates were created using the Kaplan Meier method, and compared by log-rank tests. Results: The median estimated follow-up of the entire cohort (N=100) was 36 months. The median PFS was 31 months; the median OS has not been reached. The 2- and 3-year OS estimates were 93% and 83%, respectively. 16% patients were deemed high-risk by at least one of the 3 tests (cytogenetics, FISH or PCLI). Response rates (PR or better) were 81% versus 89% in the high-risk and standard risk groups, respectively, P=NS; corresponding values for CR plus VGPR rates were 38% and 45% respectively. The median PFS was 18.5 months in high-risk patients compared to 37 months in the standard-risk patients (n=84), P<0.001(Figure). Corresponding values for TTP were 18.5 months and 36.5 months, respectively, P=<0.001. OS was not statistically significant between the two groups; 92% 2-year OS was noted in both the groups. Overall, 95 patients had at least one of the 3 tests to determine risk, while 55 patients could be adequately stratified based on the availability of all the 3 tests, or at least one test result that led to their inclusion in the high-risk category. The significant difference in PFS persisted even when the analysis was restricted to the 55 patients classified using this stringent criterion; 18.5 months vs. 36.5 months in the high-risk and standard- risk groups respectively; P<0.001. In a separate analysis, patients who underwent SCT before the disease progression were censored on the date of SCT to negate its effect, and PFS was still inferior in the high-risk group (p=0.002). Conclusion: The TTP and PFS of high-risk MM patients are inferior to that of the standard-risk patients treated with Rev-Dex, indicating that the current genetic and proliferation-based risk-stratification model remains prognostic with novel therapy. However, the TTP, PFS, and OS obtained in high-risk patients treated with Rev-Dex in this study is comparable to overall results in all myeloma patients reported in recent phase III trials. In addition, no significant impact of high-risk features on OS is apparent so far. Longer follow-up is needed to determine the impact of risk stratification on the OS of patients treated with Rev-Dex. Figure Figure

Prospective Analysis of TEL and MLL Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia: A Children’s Oncology Group Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 218-218
Author(s):  
Jeffrey Rubnitz ◽  
David Wichlan ◽  
Meenakshi Devidas ◽  
Jonathan Shuster ◽  
Joanne Kurtzberg ◽  
...  
Keyword(s):  
High Risk ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Gene Rearrangements ◽  
High Risk Patients ◽  
Favorable Prognosis ◽  
Risk Patients ◽  
Gene Status ◽  
Standard Risk

Abstract In a retrospective study, we previously demonstrated that TEL gene rearrangements, representing the TEL-AML1 fusion created by the t(12;21), conferred a favorable prognosis among children with newly diagnosed acute lymphoblastic leukemia (ALL). In 1996, we undertook a prospective study of patients greater than one year of age with B-precursor ALL consecutively enrolled on the ALinC16 study to confirm this result in an independent cohort of patients with extended follow up, to determine the incidence of TEL and MLL gene rearrangements, and to determine if TEL gene status should be used for risk classification. Among 928 cases studied, TEL gene rearrangements were detected in 244 (26%), including 29% of standard-risk and 21% of high-risk cases by the National Cancer Institute/Rome criteria. TEL-rearranged cases had a median age of 4.4 years (91% < 10 years) and a median presenting leukocyte count of 12 × 109/L (81% < 50 × 109/L). Cases with germline TEL had similar features, with a median age of 5.0 years and a median presenting leukocyte count of 12 × 109/L. At a median follow-up of 7.8 years, the 5-year event-free survival (EFS) ± SE for patients with TEL rearrangements was 86% ± 2%, compared to 72% ± 2% for those with germline TEL (p<0.0001). TEL rearrangements were associated with a favorable outcome among standard risk patients (5-yr EFS 88% ± 3% vs. 78% ± 2%, p=0.001) as well as high risk patients (5-yr EFS 81% ± 5% vs. 62% ± 3%, p=0.003). TEL rearrangements were associated with a favorable outcome among patients with rapid early responses to therapy (5-yr EFS 87% ± 2% vs. 75% ± 2%, p=0.0002), but the association did not attain statistical significance among those with slow early responses (5-yr EFS 71% ± 12% vs. 56% ± 6%, p=0.16). Overall, patients with TEL rearrangements had an outcome similar to that of patients with trisomies 4 and 10 (5-yr EFS 86% ± 2% vs. 82% ± 3%, p=0.18). By contrast, MLL rearrangements were detected in only 19 cases (2%) and the 5-yr EFS for patients with this genetic abnormality was 58% ± 11%, compared to 76% ± 1% for those with germline MLL (p=0.02). MLL rearrangements were associated with a significantly worse outcome among standard-risk patients (5-yr EFS 55% ± 2% vs. 82% ± 2%, p=0.01), but not among high-risk patients (5-yr EFS 63% ± 2% vs. 66% ± 3%, p=0.57). However, these findings should be interpreted with caution because of the small number of patients with MLL rearrangements in each risk group. The finding of TEL rearrangements in association with a favorable prognosis among both standard-risk and high-risk patients indicates that TEL gene status should be incorporated into current risk classification schemes for childhood ALL. We suggest that patients with TEL rearrangements and good early responses to therapy should be assigned to lower-risk treatment protocols.

scholarly journals Effects of Delayed Radical Prostatectomy and Active Surveillance on Localised Prostate Cancer—A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3274
Author(s):  
Vinson Wai-Shun Chan ◽  
Wei Shen Tan ◽  
Aqua Asif ◽  
Alexander Ng ◽  
Olayinka Gbolahan ◽  
...  
Keyword(s):  
High Risk ◽  
Radical Prostatectomy ◽  
Meta Analysis ◽  
Expectant Management ◽  
Intermediate Risk ◽  
Active Monitoring ◽  
High Risk Patients ◽  
Oncological Outcomes ◽  
Risk Patients ◽  
Randomised Controlled

External factors, such as the coronavirus disease 2019 (COVID-19), can lead to cancellations and backlogs of cancer surgeries. The effects of these delays are unclear. This study summarised the evidence surrounding expectant management, delay radical prostatectomy (RP), and neoadjuvant hormone therapy (NHT) compared to immediate RP. MEDLINE and EMBASE was searched for randomised controlled trials (RCTs) and non-randomised controlled studies pertaining to the review question. Risks of biases (RoB) were evaluated using the RoB 2.0 tool and the Newcastle–Ottawa Scale. A total of 57 studies were included. Meta-analysis of four RCTs found overall survival and cancer-specific survival were significantly worsened amongst intermediate-risk patients undergoing active monitoring, observation, or watchful waiting but not in low- and high-risk patients. Evidence from 33 observational studies comparing delayed RP and immediate RP is contradictory. However, conservative estimates of delays over 5 months, 4 months, and 30 days for low-risk, intermediate-risk, and high-risk patients, respectively, have been associated with significantly worse pathological and oncological outcomes in individual studies. In 11 RCTs, a 3-month course of NHT has been shown to improve pathological outcomes in most patients, but its effect on oncological outcomes is apparently limited.

scholarly journals LINC-28. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH MEDULLOBLASTOMA TREATED AT THE NATIONAL CANCER INSTITUTE (INCA) IN RIO DE JANEIRO, BRAZIL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii383-iii384
Author(s):  
Gabriela Oigman ◽  
Diana Osorio ◽  
Joseph Stanek ◽  
Jonathan Finlay ◽  
Denizar Vianna ◽  
...  
Keyword(s):  
High Risk ◽  
Maternal Education ◽  
Survival Outcomes ◽  
Middle Income ◽  
Female Ratio ◽  
High Risk Patients ◽  
Presenting Symptoms ◽  
Risk Patients ◽  
Epidemiological Characteristics ◽  
Standard Risk

Abstract BACKGROUND Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. Brazil is an upper-middle income country according to World Bank, with features of LMIC and HIC. METHODS We conducted a retrospective review of 126 children (0–18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively; overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS The male/female ratio was 1.42 and the median age at diagnosis was 7.9 years. Headache (79%) and nausea/vomiting (75%) were the most common presenting symptoms. The median time from onset of symptoms to surgery was 50 days. The OS for standard-risk patients was 69% and 53% for high-risk patients. Patients initiating radiation therapy within 42 days after surgery (70.6% versus 59.6% p=0.016) experienced better OS. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.025). Patients who lived &gt;40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS These findings suggest that socioeconomic factors, education, early diagnosis and continuous data collection, besides oncological treatment must be adressed to improve the survival of children with MB.

Efficacy of NSAIDs versus radiotherapy for heterotopic ossification prophylaxis following total hip arthroplasty in high-risk patients: a systematic review and meta-analysis

2021 ◽  
pp. 112070002199111
Author(s):  
Jacob Shapira ◽  
Mitchell J Yelton ◽  
Jeffery W Chen ◽  
Philip J Rosinsky ◽  
David R Maldonado ◽  
...  
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Meta Analysis ◽  
Comparable Efficacy ◽  
Total Hip ◽  
High Risk Patients ◽  
Randomised Control Trials ◽  
Risk Patients

Background: The aims of this systematic review were: (1) to investigate the prophylactic effect of radiotherapy (RT) and NSAIDs in high-risk patients following total hip arthroplasty (THA); and (2) to compare the efficacy of non-selective and COX-II selective NSAIDs in preventing post-THA HO, utilising a meta-analysis of randomised control studies. Methods: The PubMed, Embase, and Cochrane Databases were searched for articles regarding HO following THA in March 2019. Studies were included if they contained data regarding HO incidence after THA or contained data regarding HO prophylaxis comparison of NSAIDs and/or RT in terms of dosage or duration. Results: 24 studies reported on populations that were not at high-risk for HO. These studies reported between 47.3% and 90.4% of their patient populations had no HO formation; between 2.8% and 52.7% had mild formation; and between 0.0% and 10.4% had severe formation. A total of 13 studies reported on populations at high-risk for HO. Studies analysing RT in high-risk patients reported between 28.6% and 97.4% of patients developed no HO formation; between 1.9% and 66.7% developed mild HO formation; and between 0.0% and 11.9% developed severe HO formation. Studies analysing NSAID treatment among high-risk populations reported between 76.6% and 88.9% had no HO formation; between 11.1% and 23.4% had mild HO formation, and between 0.0% and 1.8% had severe HO formation. 9 studies were identified as randomised control trials and subsequently used for meta-analysis. The relative risk for COX-II in developing any HO after THA was not significantly different compared to non-selective NSAIDs (RR 1.00; CI, 0.801–1.256; p = 0.489). Conclusions: NSAIDs prophylaxis for HO may have better efficacy than RT in high-risk patients following THA. Non-selective and COX-II selective NSAIDs have comparable efficacy in preventing HO. Factors such as medical comorbidities and side-effect profile should dictate the prophylaxis recommendation.

Sign in / Sign up

Export Citation Format

Share Document