CLINICAL NEWS that led to hospitalization occurred in 59.7 percent of RCT-ineligible and 55.6 percent of RCT-eligible patients . Multivariate analyses identified hemoglobin < 8 g / dL , creatinine level > 2.5 mg / dL , previous venous thromboembolism , previous malignancy , ISS stage , and ECOG performance status as being associated with greater risk of a serious AE ( see TABLE 4 ).
“ Safety is a common endpoint of RCTs , and the perceived increased safety risks of clinical trials have been identified as a barrier to participation ,” the researchers noted . “ However , results of this analysis suggest that patients with newly diagnosed myeloma who are RCT-ineligible are no more likely to experience serious AEs or become hospitalized than RCT-eligible patients .”
These data identify specific criteria and parameters that have no effect on survival or serious AEs , the authors observed ,
TABLE 4 . Multivariate Analysis of Incidence Ratios ( IRs ) of Serious AEs to RCT Exclusion Criteria
Exclusion Criteria |
IR |
95 % CI |
p Value |
ECOG PS ( 3 or 4 vs . < 3 ) |
1.34 |
1.07-1.68 |
0.012 |
History of VTE |
1.64 |
1.41-1.90 |
< 0.001 |
ISS stage ( I or II vs . III ) |
1.24 |
1.11-1.38 |
< 0.001 |
Previous invasive malignancy |
1.17 |
1.03-1.32 |
0.016 |
Creatinine level > 2.5 mg / dL |
1.19 |
1.06-1.33 |
0.004 |
AEs = adverse events ; RCT = randomized , controlled trial ; ECOG PS = Eastern Cooperative Oncology Group performance status ; VTE = venous thromboembolism ; ISS = International Staging System
including absolute neutrophil count level ≤1.5 × 10 9 / L , elevated aspartate or alanine aminotransferase , hemoglobin ≤8 g / dL , and previous HIV or hepatitis infection .
“ Re-evaluation of RCT eligibility criteria is needed to improve enrollment without compromising the ability of trials to determine treatment effects ,” the authors concluded . “ These parameters could potentially be eliminated from RCT eligibility criteria , [ which ] would lead to a broader patient population and accelerate enrollment without affecting the integrity of a trial or safety of patients .”
The study is limited by its inclusion of only newly diagnosed patients , which
Print-only content
“Re-evaluation of RCT eligibility criteria is needed to improve enrollment ...”
— JATIN J . SHAH , MD
is not generalizable to the relapsed / refractory , real-world population . Also , “ this analysis was able to show an association between certain eligibility criteria and serious AEs , but causality cannot be established ,” the authors wrote . Future studies should examine outcomes related to race , as the present study found that 53 percent of the African-American subpopulation were deemed RCT-ineligible , compared with 39 percent in the white subpopulation ( p < 0.001 ).
Celgene Corporation provided funding for this study .
Contributing authors report financial support from Celgene Corporation , Millennium Pharmaceuticals , Onyx Pharmaceuticals , Novartis , and Array Biopharma .
REFERENCE
Shah JJ , Bonjour R , Lazaretto C , et al . Analysis of common eligibility criteria of randomized controlled trials in newly diagnosed multiple myeloma patients and extrapolating outcomes . Clin Lymphoma Myeloma Leuk . 2017 ; 17:575-83 .
ASH Clinical News 61