e19506 Background: Chimeric antigen receptor (CAR) T-cell immunotherapy is a revolutionary treatment modality which has gained attention for its potential in treating multiple refractory hematological malignancies. Significant toxicities associated with CAR T- cell therapy remain a major concern. Cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are seen early on post CAR-T cell therapy. To date, the treatment of ICANS has largely been limited to supportive care and corticosteroids. More recently, some early clinical data investigated the use of Anakinra as a promising agent in prevention and treatment of severe ICANS. Methods: We analyze three cases in which Anakinra was used to treat high-grade ICANS concurrently with high dose steroids. Results: A 51-year-old woman with high grade DLBCL and secondary CNS involvement was treated with Tisagenlecleucel CAR-T therapy. On day 2, patient became altered and was diagnosed with ICANS Grade II. High dose steroids were started leading to resolution of ICANS. However, patient’s mentation worsened by day 7, progressing to ICANS Grade IV by day 8, and Anakinra 100 mg IV was added to the steroid regimen. By day 11, after 4 doses of Anakinra, patient’s neurotoxicity completely resolved. Patient achieved a PR by day 30 after CAR-T cell infusion. In the second case, a 65-year-old man with DLBCL and leptomeningeal involvement developed ICANS Grade II on day 1 after Tisagenlecleucel CAR-T therapy and was started on high dose steroids. By day 4, neurotoxicity worsened and progressed to ICANS Grade IV. On day 5 patient was transferred to ICU for a mechanical ventilation, and Anakinra 100 mg IV was added and continued daily for 7 days. By day 12, neurotoxicity improved to ICANS grade II and patient was extubated. Meanwhile, high dose steroids were tapered. His condition acutely worsened by day 19, prompting transfer to the ICU and re-initiation of Anakinra concurrently with steroids. His family decided against further escalation of care on day 22. Patient was transitioned to comfort care and died 23 days post CAR-T cell infusion. In the third case, a 65-year-old man with mantle cell lymphoma was treated with Brexucabtagene autoleucel CAR-T therapy. On day 8, patient developed ICANS Grade I which rapidly progressed to Grade IV. High dose steroids were started and ICANS improved to Grade II on Day 9. However, on Day 10 patient’s mentation again worsened and one dose of Anakinra 100mg IV was added to the steroid regimen. By day 11, ICANS completely resolved, and patient was ultimately discharged home on day 15. Patient was able to achieve interval CR by day 30 after CAR-T cell infusion. Conclusions: In the reported cases, ICANS improved following administration of Anakinra, adding support to the idea that Anakinra may be beneficial in treatment of high-grade ICANS. Future studies are needed to better understand the overall efficacy and the ideal timeline for administration.
410 Background: MB is a serious complication in patients with CAVTE receiving treatment with DOAC or LMWH. The most recent meta-analysis of the four major RCT showed that MB events rate were similar among the DOAC and LMWH group, however, it was noted that MB occurred at GU site 4.9 times more in DOAC than LMWH patients. While GUCA (e.g. bladder and testicular) are considered to be high-risk based on the Khorana Score, they were underrepresented among the RCT ( < 12%). We present a Real-World retrospective cohort study analyzing the MB rates in patients presenting with GU-CAVTE treated either by a DOAC or LMWH compared to those of the RTC. Methods: We performed a retrospective chart review of patients with a diagnosed GUCA and VTE who presented to The University of Arizona Cancer Center (UACC) and were subsequently placed on anticoagulant therapy with either a DOAC or LMWH from 11/2013-4/2020. MB outcome was defined as documented Hgb drop of ≥2 g/dL, ≥2 units of PRBC, MB in a critical site, or contributing to death. MB was extracted and compared from the SELECT D, ADAM VTE, and Caravaggio for DOAC and Hokusai for the LMWH control arm with the GUCA subgroup. Recurrent VTE was collected. In situations where there was insufficient data to categorize individuals, those individuals were excluded from the analysis. The proportion of MB reported in each study were compared using a binomial test. Results: Our review included 56 patients with similar baseline characteristics to the RCT, who were prescribed enoxaparin (n = 13), apixaban (n = 27) and rivaroxaban (n = 16). Our UACC data was compared to the RCT reported MB outcomes with rivaroxaban (12% vs 8%, [p = 0.63]), apixaban (11% vs 6%, [p = 0.40]), and LMWH (both 0 vs 1% [p = 0.67]). No statistical difference among DOAC selection [p = 0.90]. Our UACC rate of MB in patients with GUCA for both DOAC combined versus LWMH were 11.6% (5/43) and 0% [p = 0.1910], compared to the RCT GU subgroup was 5.7% (6/104) [p = 0.02] and 0.6% (1/175) [p = 1.0], respectively. Furthermore, our data found no statistical significance difference among the recurrent VTE rate among DOAC, LMWH, UACC Retrospective or RCT events. Conclusions: In agreement with the four major RCT, our study demonstrated that patients with high-risk GUCA and underlying VTE treated with a DOAC had a non-significant higher incidence of MB compared to those treated with LMWH. Further, our Real-World experience showed that GUCA DOAC had a significantly higher MB event rate compared to the RCT subgroup population. We acknowledge there are inherent biases in all retrospective studies and RCT. These data support the idea that DOAC should be further studied and used with caution in patients with a high risk of bleeding. We recommend LMWH being the safest anticoagulation modality for High-Risk Bleeding GU malignancy.
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