Preliminary Exploration of the Stimulating Effect of Pomalidomide on BCMA-CART in the Treatment of Multiple Myeloma Patients

Research Background: BCMA-CART treatment can give patients with relapsed and refractory multiple myeloma a chance of remission, but because the patient's own lymphocytes are poor in number and function, poor autologous CART cell expansion or failure to expand will affect the efficacy of CART. It is necessary to explore ways to improve the curative effect of CART so as to increase the remission rate. Research purposes The purpose of the study was to observe the changes in symptoms, signs, and vital signs of patients with pomalidomide in the early stage after BCMA-CART reinfusion, analyze the changes in cytokines and CART expansion after oral pomalidomide, and summarize the symptoms of such patients Disease remission rate and survival status. Research methods Collect the clinical characteristics of patients who took pomalidomide orally within one month after BCMA-CART cell reinfusion in our hospital from January 2019 to July 2021, and count the symptoms and signs of patients with pomalidomide before and after CART. Compare the values of cytokine and CART cell expansion before and after CART reinfusion to explore the synergistic effect of pomalidomide with CART. Research result From January 2019 to July 2021, a total of 5 patients with multiple myeloma who took pomalidomide orally within 1 month after BCMA-CART cell reinfusion were treated in our department from January 2019 to July 2021. There were 2 male patients and 3 female patients. The median age is 63 years (35-70). The median number of patients' previous treatment lines is 7 (3-18), of which 3 patients(3/5) have had previous autologous hematopoietic stem cell transplantation. The number of reinfused BCMA-CART cells in 5 patients was 8.13 (0.11-16.5)*105/kg, the median time of oral pomalidomide was 14 (8-19) days of CART reinfusion, and the dose was 1 case (1/ 5) 4 mg 1/day for patients, 2 mg 1/day for 3 patients (3/5), 1 mg 1/5 for 1 patient (1/5); 3 patients (3/5) before pomalidomide treatment ). The number of CART cell expansion in patients was 0.00%, 0.40% in 1 case (1/5), and 7.03% in 1 case (1/5). None of them had fever. 4 patients (4/5) had fever after taking pomalidomide, the median maximum body temperature was 38.95 (38.3-40.2) ℃, and the fever occurred 1.5 (1-4) days after taking pomalidomide; The amplification of CART cells of all patients can be detected by PCR method after pomalidomide, and the start time of amplification is 5 (2-8) days after taking pomalidomide; the amplification of CART cells The highest peak occurred at 9 (4-19) days after taking pomalidomide. The peak of CART cell expansion increased by 3.86 (0.06-37.8)% compared to before treatment with pomalidomide; the CRS classification after taking pomalidomide of 4 cases (4/5) were grade 2 and 1 case (1/5) was grade 3, of which 2 cases (2/5) had ICANS. Cytokines were increased in all patients after pomalidomide. Among them, IL-6 of all cases (5/5) increased after pomalidomide, and the highest value of IL-6 appeared after pomalidomide. At 9 (5-22) days after pomalidomide administration, the increase value was 20.60 (16.16-380.23) pg/mL; among the 4 patients that can be counted, TNF-α level of 4 patients (4/4) were increased after pomalidomide administration, the highest value of TNF-α appeared at 7.5 (6-8) days after pomalidomide administration, and the increase value was 21.825 (11.60-32.81) pg/mL. All 4 countable patients had higher soluble CD25 after pomalidomide administration, and the highest value of soluble CD25 appeared 11 (6-14) days after pomalidomide administration, and the value of increase was 7987 (3765-26173) pg/Ml. Gamma interferon of all 4 countable patients increased after pomalidomide administration, and the highest value of gamma interferon appeared in 9.5 (2-14) days after pomalidomide use, the increase value was 18.49 (5.3-587.8) pg/ml. The efficacy of 5 patients evaluated after 1 month after BCMA-CART was 2 cases (2/5) with stable disease, 2 cases (2/5) with partial remission, and 1 case (2/5) with disease progression. As of the deadline for submission, 5 patients are currently alive, and the median OS is 113 (42-236) days after CART reinfusion. Analysis conclusion Pomalidomide can promote the expansion and activation of CART and stimulate the release of cytokines in the early stage after BCMA-CART treatment. Whether it can enhance the anti-tumor effect of CART remains to be further studied. Disclosures No relevant conflicts of interest to declare.

Screening of hemophagocytic lymphohistiocytosis in children with severe sepsis in pediatric intensive care

Background: We sought to screen for clinical and laboratory features of hemophagocytic lymphohistiocytosis among pediatric patients with severe sepsis. Methods: We conducted a retrospective study that analyzed the clinical and laboratory data of 70 pediatric patients who died of severe sepsis. Medical records were revised for the presence of fever, splenomegaly, pancytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. Soluble CD25 was measured in stored samples. Results: Patients’ ages ranged between 0.5 and 11 years with median (interquartile range) 2 (1–5). All patients had fever (≥38.5 °C) and pancytopenia, 58 (82.9%) hepatosplenomegaly, 36 (51.4%) lymphadenopathy, 37 (52.9%) had ferritin >500 ng/ml, 20 (28.6%) had fibrinogen <1.5 mg/ml, 14 (20%) had fasting triglycerides >264 mg/dl while 5 (7.1%) had soluble CD25 >2400 U/ml. Twenty-five (35.7%) patients fulfilled at least 5/6 of the hemophagocytic lymphohistiocytosis-2004 diagnostic criteria. Multivariate backward binary logistic regression analysis revealed lymphadenopathy as an independent predictor for hemophagocytic lymphohistiocytosis criteria fulfilment with odds ratio of 23.9. Fibrinogen had the best performance in discriminating hemophagocytic lymphohistiocytosis fulfilling from non-fulfilling groups (cut-off value: <1.8 mg/ml), followed by ferritin/erythrocyte sedimentation rate ratio (cut-off value: >17). Conclusion: There is a significant clinical and laboratory overlap between hemophagocytic lymphohistiocytosis and severe sepsis, making the syndromes difficult to distinguish. The use of current hemophagocytic lymphohistiocytosis-2004 diagnostic criteria should be applied cautiously in those patients.