Updates in Malignant Hematology
The 2021 American Society of Clinical Oncology ( ASCO ) Annual Meeting took place virtually June 4-8 . The program featured hundreds of on-demand and broadcast sessions in which participants discussed trends in cancer research and practice-changing data from clinical trials . Here , we cover the latest advances in malignant hematology shared at the meeting , including research supporting prophylactic letermovir in transplant and questioning VTE prediction tools in gynecologic cancers .
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Does Khorana Score Accurately Predict VTE in Patients With Uterine and Ovarian Cancer ?
At the 2021 ASCO Annual Meeting , researchers shared results from two studies examining the Khorana score for predicting venous thromboembolism ( VTE ) in patients with gynecologic cancers .
The Khorana score assigns risk according to cancer type ( with gynecologic cancers defined as highrisk cancers ), hemoglobin level , body mass index , and pre-chemotherapy platelet and leukocyte counts . Patients with higher scores are more likely to experience VTE . Clinical practice guidelines recommend that patients with Khorana scores ≥2 who are on systemic chemotherapy receive thromboprophylaxis .
However , both studies found that the tool , which has been validated to identify patients with cancer who are at high risk for VTE and would benefit from thromboprophylaxis , did not accurately predict VTE in this patient population .
In the first study , Ellen Marcus , BS , a medical student from Albert Einstein College of Medicine and Montefiore Medical Center in New York , and colleagues , examined the predictive ability of the Khorana score in 427 patients who were diagnosed with ovarian cancer at her institution between 2000 and 2020 . Scores were retrospectively calculated for all patients who received chemotherapy based on their pre-chemotherapy lab values .
Patients in the cohort had a median follow-up of 33.7 months ( range = 13.3-61.1 ). During that time , 142 patients ( 31 %) underwent diagnostic testing to rule out VTE , and 62 ( 15 %) were diagnosed with VTE . The median time to VTE presentation was 8.7 months ( range = 2.7-30.3 ). Factors significantly associated with VTE included stage III-IV disease , epithelial histology , open surgery , radical tumor debulking , and presence of residual disease after surgery .
The researchers found that , compared to patients with a score of 1 , patients with Khorana scores of 2 or 3 were not significantly more likely to develop VTE during chemotherapy ( odds ratios [ ORs ] = 1.73 and 0.89 ). However , patients with scores of 4 were nearly seven times more likely to develop VTE while on chemotherapy .
In addition , in a multivariable model , “ a Khorana score of 2 or higher could explain only 0.86 % of the variability in predicting VTE ,” the authors wrote . Only stage III-IV disease and hyperlipidemia were significantly associated with VTE after adjustment .
Overall , the results from this analysis suggest that , although patients with ovarian cancer are at high risk of developing VTE many months after diagnosis and initiation of chemotherapy , a higher Khorana score did not predict the patients most likely to develop VTE .
“ Future models should be developed and validated in large population-based cohorts to determine if there is a more accurate strategy to identify women with ovarian cancer who are at risk for VTE ,” the authors concluded .
“ Although validated in other cancer types , the Khorana score was found to be a poor predictor of VTE in this population .”
— Vincent Wagner , MD
In the second study , Vincent Wagner , MD , from The Ohio State University Wexner Medical Center and James Cancer Hospital in Columbus , and colleagues , reviewed the predictive value of the Khorana score in another retrospective cohort of 265 patients with uterine cancer who were receiving either neoadjuvant or adjuvant chemotherapy . Researchers evaluated the incidence of VTE in the 12 months following the first cycle of chemotherapy .
Most patients in the cohort were obese ( 60.4 %) and ≥60 years old ( 70.9 %). A total of 24 patients ( 9.1 %) developed VTE , which was higher , but not statistically different , among patients receiving neoadjuvant compared with adjuvant chemotherapy ( 13.5 % vs . 8.3 %; p = 0.35 ). The authors found no statistically significant correlations between the development of VTE and pathologic data , demographics , or treatment factors such as hysterectomy or radiation treatment .
The proportion of patients with high Khorana scores ( defined as either ≥2 or ≥3 ) was similar between groups . In the whole cohort , high Khorana score did not significantly predict VTE ; however , the model using ≥3 was more predictive than the ≥2 model typically used in clinical practice guidelines ( OR = 1.15 ; p = 0.7326 ). For patients who received neoadjuvant chemotherapy , neither model was predictive of VTE , the researchers added , while a Khorana score ≥3 was a better prediction model in those who received adjuvant chemotherapy ( OR = 1.56 ; p = 0.4213 ).
“ Although validated in other cancer types , the Khorana score was found to be a poor predictor of VTE in this population ,” the authors concluded . “ At this time , use of the Khorana score to guide routine thromboprophylaxis in patients undergoing chemotherapy for uterine cancer should be used with caution .”
Study authors report no relevant conflicts of interest .
References
1 . Marcus E , Kuo DYS , Nevadunsky NS , et al . Association of the Khorana Score with development of venous thromboembolism in ovarian cancer . Abstract # 5555 . Presented at the 2021 ASCO Annual Meeting , June 4-8 , 2021 .
2 . Wagner V , Levine M , Piver R , et al . Use of Khorana score to predict VTE in patients undergoing chemotherapy for uterine cancer . Abstract # 5589 . Presented at the 2021 ASCO Annual Meeting , June 4-8 , 2021 .
Investigating the Combination of Ivosidenib Plus Venetoclax and Azacitidine in IDH-Mutated Myeloid Malignancies
In a small study of patients with IDH1-mutated myeloid malignancies , treatment with ivosidenib plus venetoclax , with or without azacitidine , had an acceptable safety profile and led to high rates of complete responses in patients with acute myeloid leukemia ( AML ). Curtis Andrew Lachowiez , MD , from The University of Texas MD Anderson Cancer Center , shared interim results from this study at the 2021 ASCO Annual Meeting .
Research has shown that malignancies that harbor the IDH1-mutation demonstrate increased reliance on the anti-apoptotic protein BCL2 , Dr . Lachowiez explained , suggesting an enhanced susceptibility to the BCL2 inhibitor venetoclax . In this phase Ib / II trial , investigators enrolled a total of 25 adults with IDH1-positive malignancies : four with myelodysplastic syndromes ( MDS ), 13 with newly diagnosed
32 ASH Clinical News August 2021