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Chimeric antigen receptor (CAR) T-cell therapy is effective in relapsed/refractory large B-cell lymphoma and results in a unique toxicity profile, namely cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. The hyper-inflammatory state associated with these toxicities has been suggested to increase the risk of thrombosis. We conducted a retrospective analysis of patients treated with axicabtagene ciloleucel (axi-cel) to assess the rate of thrombosis with axi-cel therapy from the time of CAR T-cell infusion until the end of hospitalization, when performed in the inpatient setting, or up to day +30 when performed in the outpatient setting. Ninety-two (95%) of 97 patients were hospitalized during axi-cel therapy and 85 (88%) developed CRS. Fifty-five patients (57%) received concurrent anticoagulation (53 as prophylaxis). Patients with prior VTE did not have progression or evidence of new VTE. Only 2 (2.1%) patients developed VTE. These results demonstrate a low-risk for thrombosis in axi-cel recipients. [ABSTRACT FROM AUTHOR]

Introduction: Hypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi‐cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B‐cell lymphoma. Methods: We conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi‐cel. Results: This analysis included 81 patients. Two patients had no available SA levels preceding axi‐cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P =.018). There was no difference in 1‐year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P =.81) and (74% vs 73%, P =.97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups. Conclusion: Notwithstanding the limitations related to the relatively small sample size, axi‐cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings. [ABSTRACT FROM AUTHOR]

IgG4‐related disease (IgG4RD) with intracranial involvement is rare. We report a 56‐year‐old male who had an excellent response to rituximab and dexamethasone after going undiagnosed for 5 years. After 3 years of rituximab maintenance, he has no evidence of disease on brain MRI. [ABSTRACT FROM AUTHOR]

Oxaliplatin is one of the most commonly used drugs for patients with colorectal cancer. It has rarely been associated with disseminated intravascular coagulation (DIC) with only 3 previously reported cases. In all those instances, the patients had started receiving oxaliplatin, developed evidence of DIC during the course of planned treatment, and recovered with supportive care. We report a case of a 71-year-old man with colorectal cancer treated successfully with an oxaliplatin- based regimen who had disease relapse after 3 years. When treated again with oxaliplatin, he developed signs of an acute hypersensitivity reaction, and eventually had signs and symptoms consistent with DIC despite appropriate management. This case is unique in that a DIC reaction evolving from a hypersensitivity reaction occurred after the patient had already tolerated the drug years earlier. It suggests a possible immune-mediated etiology to this rare occurrence that should be kept in mind while utilizing this commonly employed drug. [ABSTRACT FROM AUTHOR]

Axicabtagene ciloleucel (Axi-cel) is an autologous chimeric antigen receptor (CAR) T-cell therapy which is effective in relapsed/refractory (R/R) anti-CD19 B-cell leukemia and lymphomas. Axi-cel is associated with unique toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Management of these toxicities often requires ICU admission. Scoring systems have been developed to grade severity of these toxicities and help guide treatment escalation as needed; however, they provide little insight into duration of ICU stay. C-reactive protein (CRP) and ferritin are serum inflammatory markers associated with onset and persistence of CAR-T cell related toxicity. Here, we examine the relationship between these serum inflammatory markers and the duration of ICU stay in CAR-T Cell therapy recipients. We conducted a retrospective analysis of patients (pts) treated with axi-cel across two Mayo Clinic campuses (Jacksonville and Phoenix) from 06/01/2018 until 07/01/2019. Primary objective was to examine the relationship between serum ferritin and CRP levels with need for and length of ICU stay in axi-cel treated pts. Our study population consisted of 18 pts (11 males, 61%), median age of 51 (26-67) years. Nine were admitted to the ICU during their initial hospitalization. The median time from axi-cel infusion to ICU admission was 4 (2-8) days with a median ICU length of stay of 4 (2-24) days. All 9 admitted pts developed CRS: grade 1 (1), grade 2 (7), and grade 3 (1); 7 pts developed ICANS: grade 2 (1), grade 3 (1) and grade 4 (5). Eight of the 9 non-ICU pts developed CRS: grade 1 (5) and grade 2 (3). Three pts developed grade 1 ICANS. Grade of CRS and ICANS were higher in ICU pts vs non-ICU pts (p=0.01 and p=0.001, respectively). There was no correlation between the severity of CRS and length of ICU stay (correlation of 0.07, p=0.86) or severity of ICANS and length of ICU stay (correlation of 0.36, p=0.35). Initial median CRP level at infusion was higher in ICU vs. non-ICU pts (25.2 mg/L vs. 13.9 mg/L); however, this difference was not significant, p=0.38. Initial ferritin levels at infusion were over 2-fold higher, albeit not statistically significant, in ICU pts (837 mcg/L vs 387 mcg/L, p=0.21). The median CRP at the time of ICU admission was 54.1 mg/L (3.2-341) mg/L. There was no significant correlation between CRP levels at time of ICU admission and length of ICU stay (correlation of 0.067, p = 0.86). The median ferritin level at the time of ICU admission was 2010mcg/L (344-10943). There was a strong direct correlation between serum ferritin levels and length of ICU stay (correlation of 0.93, p = 0.0003). This study showed that an elevated ferritin level at the time of escalation of medical care may be indicative of anticipated prolonged ICU hospitalization in axi-cel recipients. [ABSTRACT FROM AUTHOR]

Axi-cel is an autologous anti-CD19 chimeric antigen receptor T-cell therapy approved for treatment of CD19+ relapsed/refractory large B-cell lymphoma. Axi-cel is associated with unique toxicities, namely cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our understanding of these toxicities continues to evolve and identification of predictive biomarkers is essential to optimize management strategies for such toxicities. Albumin is a known inflammatory marker; however, its relation to axi-cel toxicities remains unclear. We conduct this analysis to assess the significance of a decrease in serum albumin levels and its relation to ICANS. We conducted a retrospective analysis of all patients treated with axi-cel across the 3 Mayo Clinic campuses (Rochester, Jacksonville, and Phoenix) from 06/01/2018 until 06/01/2019. Albumin levels were collected at baseline (within 5 days prior to axi-cel infusion), time of CRS onset, time of ICANS onset and at Day +30. A total of 54 patients (male=39, 72%) with a median age of 53 (26-67) years received axi-cel during the study period. Median number of prior lines of therapy was 3 (2-8). Number of patients who developed ICANS was 33 (61%) patients; 4 patients did not have serum albumin levels available at all specified time points, therefore, 29 patients constituted the study cohort (patient characteristics are shown in Table 1, no statistically significant difference was noted between groups). Of patients who developed ICANS, 7 patients (24%) had low serum albumin (< 3.5 g/dL) at baseline. Twenty three patients (80%) had a decrease in serum albumin at onset of ICANS with a median decrease from baseline of 0.8 g/dL (range: 0.1-1.3), representing a median percentage decrease from baseline of 19% (2%-36%) (Figure 1). Recovery of serum albumin to a normal range at day +30 was observed in 21 (72%) patients with a median increase in serum albumin level of 0.7 g/dL (0.2-2.3). The magnitude of this decrease was not observed with onset of CRS or in patients with only CRS (without ICANS). A decrease in serum albumin level appears to serve as a predictive marker of ICANS onset and a subsequent increase appears to herald its resolution. If validated in larger studies, use of serum albumin could potentially serve as a cost-effective method compared to more expensive currently used serum markers. [ABSTRACT FROM AUTHOR]