Search

Background 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. Methods 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. Results 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 ( Conclusions 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.

Background 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. Methods 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. Results 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). Conclusions 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.

CONTEXT AND OBJECTIVE: Refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) is a provisional entity included in the MDS/MPN overlap syndromes, with features of refractory anemia with ring sideroblasts (RARS) and thrombocytosis (platelet count ³ 450 x 10/L), recently renamed MDS/MPN with ring sideroblasts and thrombocytosis. Management of RARS-T is extrapolated from MDS and MPN treatment options namely for alleviating symptoms of anemia and, occasionally, for thrombocytosis. Individual case reports have suggested that lenalidomide may be effective in treating RARS-T. In non-del 5q, low-risk MDS, 25% of patients (pts) became red blood cell transfusion independent (RBC-TI). In the phase II study of lenalidomide in non-del 5q lower risk MDS, 35% of pts with RARS treated with lenalidomide achieved RBC-TI. The primary objective of this study is to evaluate a series of pts with RARS-T and compare hematological improvement (HI) responses among different treatment options. METHODS: This is a retrospective, single-center study. Patients with RARS-T were identified from the MDS Database at Moffitt Cancer Center. Samples for somatic mutation testing were obtained at time of referral. Descriptive statistics were used to describe baseline characteristics and response rates to treatment. The primary endpoint was HI using international working group criteria (IWG) 2006. The median overall survival (OS) was calculated from time of diagnosis. RESULTS: We identified 33 pts with RARS-T. The mean age was 67 years (38-80), 15 pts were male (45.5%), and majority were Caucasians (n=27, 82%). According to international prognostic scoring system (IPSS), 24 patients (73%) were low risk and 9 pts (27%) were int-1 risk. By revised IPSS, 11 pts (33%), 18 (55%), 3 (9%), and 1 (3%) were very low, low, intermediate, and high risk, respectively. The mean WBC was 7.7 (2.8-25.7), the mean Hemoglobin was 9.9 g/dl (7.3-12.4), and the mean platelet count was 682 (372-1644). Among 20 pts who had Next generation sequencing for somatic mutations at time of referral, 19 pts (95%) had SF3B1 mutation and 4 pts (20%) had JAK-2 V617 F mutation. The median OS was 90 mo (95% CI 47-134). For pts with JAK-2 V617F mutations, the median OS was 110 mo versus 74 mo for those with wild type (p=0.24). The rate of AML transformation was 3% (one patient only). Among the 33 pts, 8 pts had no treatment (observation only), 22 pts (67%) received erythroid stimulating agent (ESA) prior to any active therapy, 2 patients received lenalidomide with no prior ESA, and 1 pt ruxolitinib with no prior ESA. Twelve pts (36%) received lenalidomide (7 as first line active therapy after ESA and 2 without prior ESA exposure) and 13 pts (33%) received azacitidine (6 as first line active therapy after ESA). The HI rate for ESA was 36% (12/22) with a median duration of ESA treatment of 33mo. The HI rate for lenalidomide was 50% (6/12) with a median duration of lenalidomide treatment of 10.3mo. Among the 9 pts who received lenalidomide as first line active therapy (2 pts without prior ESA exposure) HI rate was 56%. The HI rate for azacitidine was 15% (2/13) with a median duration of azacitidine treatment of 6.3mo. CONCLUSIONS: Pts with RARS-T had favorable outcomes, with long overall survival and a low rate of AML transformation. Rates of hematological improvement with the use of azacitidine were lower than expected. Lenalidomide is an effective treatment option and should be considered when treating patients with RARS-T. Figure. Figure. Disclosures Sallman: Celgene: Research Funding, Speakers Bureau. List:Celgene: Research Funding. Komrokji:Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau.