in a Different Vein
CLINICAL NEWS
Research from ASH ’ s online peer-reviewed journal , Blood Advances
Lenalidomide Therapy Increases VTE Risk in B-Cell Non-Hodgkin Lymphoma
Patients with B-cell non-Hodgkin lymphoma ( NHL ) treated with lenalidomide have an increased risk of developing venous thromboembolism ( VTE ) – similar to the increased risk observed in lenalidomide-treated patients with myeloma – according to results from a systematic review and meta-analysis published in Blood Advances . This risk appears to be consistent among patients with NHL who receive lenalidomide alone or in combination with biologic agents or chemotherapy .
To characterize the risk of VTE among this patient population , the authors , led by Samuel Yamshon , MD , from Weill Cornell Medicine in New York , searched literature databases ( including Ovid MEDLINE and The Cochrane Library ) to identify abstracts across all languages that assessed patients with either newly diagnosed or relapsed / refractory B-cell NHL who were treated with lenalidomide . Of 1,719 citations found in the initial review , 28 articles were included .
Researchers selected VTE events per 100 patient-cycles as the study ’ s primary outcome . A VTE event was defined as a grade ≥2 venous thrombosis ( according to National Cancer Institute Common Toxicity Criteria , the Common Terminology Criteria for adverse events , or the World Health Organization criteria ).
VTE rate was measured within three predefined cohorts :
• patients treated with lenalidomide monotherapy ( n = 698 )
• patients treated with lenalidomide plus biologic agents ( n = 357 )
• patients treated with lenalidomide plus chemotherapy ( n = 378 )
The median age among all three cohorts was between 65 and 68 years ( ranges not specified ). Patients in the lenalidomide-plus-chemotherapy group received a median of zero prior therapies , while those in the other two cohorts had a median of three prior therapies .
Overall , the 28 studies included a total of 10,332 lenalidomide treatment cycles with 77 VTE events reported . The pooled VTE rate per 100 patient-cycles among the entire B-cell NHL cohort was 0.77 events ( 95 % CI 0.48-1.12 ).
In the sub-analyses of the three cohorts , rates of the primary outcome were as follows :
• lenalidomide monotherapy : 1.09 events ( 95 % CI 0.49-1.94 )
• lenalidomide plus biologic agents : 0.49 events ( 95 % CI 0.17-0.97 )
• lenalidomide plus chemotherapy : 0.89 events ( 95 % CI 0.39-1.60 )
The authors also calculated the threeand six-month rates of VTE for the overall population ( 2.3 % and 4.5 %, respectively ), which appeared to be similar to those reported among lenalidomide-treated patients with myeloma . ( See TABLE for VTE rates among the three treatment cohorts ). “ Although meta-analysis techniques do not allow for direct significance testing across the subgroups , the single-agent group appears to be associated with a higher VTE event rate ,” the authors reported , offering several hypotheses for this association . “ A reduction in tumor burden by the addition of a second agent may account for this relatively decreased risk in those patients treated with lenalidomide and an additional agent ,” they wrote . “ A direct interaction between lenalidomide and tumor cells is a possibility as well , with lenalidomide having an effect on the vasculature and mediators of coagulation .”
“ Our systematic review and metaanalysis suggest that the rate of thrombosis in patients with lymphoma treated with lenalidomide is similar to that in multiple myeloma , where guidelines recommend VTE prophylaxis for all patients ,” Dr . Yamshon told ASH Clinical News . “ Given these similarities , and the emerging potential clinical applications of lenalidomide-containing regimens in various lymphoma populations , outpatient VTE prophylaxis should be carefully considered in patients with B-cell NHL treated with lenalidomide .”
The findings of this meta-analysis are limited by the lack of data on the total number of treatment cycles received by patients in certain included studies . In addition , this report examined studies that enrolled highly selected patients who were actively participating in clinical trials , which may limit the generalizability of the findings across the average B-cell NHL population . Also , “ although the median age , stage , and performance status throughout the three cohorts were similar , other risk factors for thrombophilia could not be further differentiated with these study reports ,” the authors noted .
“ We hope that the data will help
“ In future trials of lenalidomide in non-Hodgkin lymphoma , it might be helpful to report VTE as a defined outcome stratified to risk factors ... .”
– SAMUEL YAMSHON , MD
inform clinicians in evaluating the risks and benefits of VTE prophylaxis in this population ,” Dr . Yamshon said . “ In future trials of lenalidomide in NHL , it might be helpful to report VTE as a defined outcome stratified to risk factors such as age , comorbidities , and lymphoma subtypes , in addition to including it as an adverse event .” He added that “ a randomized controlled trial comparing VTE preventative approaches in high-risk populations also could be clinically relevant , as there is no consensus for best practices for VTE prophylaxis in this group of patients .” ●
The authors report financial relationships with Celgene .
REFERENCE
Yamshon S , Christos PJ , Demetres M , et al . Venous thromboembolism in patients with B-cell non-Hodgkin lymphoma treated with lenalidomide : a systematic review and meta-analysis . Blood Adv . 2018 ; 2:1429-38 .
TABLE . Pooled VTE Events per 100 Patient-Cycles by Treatment Modality Using Random-Effects Models
Treatment cohort
All patients treated with lenalidomide
Pooled VTE events / patient-cycle
Pooled VTE events / 100 patient-cycles
95 % CI 3-month VTE risk , % 6-month VTE risk , %
0.007685 0.77 0.48-1.12 2.3 4.5
Single-agent lenalidomide 0.0109 1.09 0.49-1.94 3.2 6.4 Lenalidomide + biologics 0.00486 0.49 0.17-0.97 1.5 2.9 Lenalidomide + chemotherapy 0.00891 0.89 0.39-1.60 2.6 5.2 VTE = venous thromboembolism
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