Early Tocilizumab Research Articles

Improvement in Cytokine Release Syndrome Management for the Treatment of AML Patients with Flotetuzumab, a CD123 x CD3 Bispecific Dart® Molecule for T-Cell Redirected Therapy

Improvement in Cytokine Release Syndrome Management for the Treatment of AML Patients with Flotetuzumab, a CD123 x CD3 Bispecific Dart® Molecule for T-Cell Redirected Therapy

Results from the Completed Dose-Escalation of the Hematological Arm of the Phase I Think Study Evaluating Multiple Infusions of NKG2D-Based CAR T-Cells As Standalone Therapy in Relapse/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients

Results from the Completed Dose-Escalation of the Hematological Arm of the Phase I Think Study Evaluating Multiple Infusions of NKG2D-Based CAR T-Cells As Standalone Therapy in Relapse/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients

PS1212 UPDATED RESULTS FROM PHASE I TRIALS ASSESSING A NKG2D CAR T‐CELL APPROACH IN RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROME PATIENTS

Background:CYAD‐01 cells are chimeric antigen receptor (CAR) T cells based on the NKG2D receptor fused to the intracellular domain of CD3ζ, and bind ligands (MICA/B, ULBP1–6) expressed by a large variety of malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Aims:A comprehensive clinical program was developed with the objective to define the optimal CYAD‐01 treatment in relapsed/refractory (r/r) AML/MDS patients (pts).Methods:The Phase I THINK trial (NCT03018405) assesses the safety and clinical activity of multiple CYAD‐01 infusions without preconditioning chemotherapy in various malignancies, including r/r AML, MDS and multiple myeloma (MM). 3 dose levels (DL) were evaluated in the dose escalation segment (3x108, 1x109 and 3x109 T‐cells/inf.). 1st cycle of treatment consists of 3 CYAD‐01 infusions every 2 weeks and a 2nd cycle of 3 CYAD‐01 infusions with a 2 week‐interval in case of no progressive disease (PD) after the 1st cycle. Additional cohorts aim to provide a dense treatment schedule at the same DL (3x 1 CYAD‐01 every week + 3x 1 CYAD‐01 every 2 weeks). The Phase I/II DEPLETHINK study (NCT03466320) evaluates the safety and preliminary efficacy of 1 CYAD‐01 infusion administered after preconditioning with cyclophosphamide and fludarabine to pts with r/r AML/MDS. A 2nd cycle of 3 CYAD‐01 without preconditioning is administered in case of no PD after 1st treatment. 3 DL (1x108, 3x108 and 1x109 cells/inf.) and 2 intervals between preconditioning and CYAD‐01 infusion are evaluated in the dose escalation segment. Data as of February 20, 2019 are presented.Results:THINK study: 16 pts were enrolled in the dose‐escalation segment of the hematological cohort, now completed. 4 pts were enrolled in cohorts with the dense schedule. In total, 7 pts experienced grade (G) 3/4 treatment‐related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 10 pts with only 2 G3 CRS (at DL2) and 1 G4 CRS (at DL3), which resolved with early tocilizumab treatment. No treatment‐related neurotoxicity AEs have been observed.Out of 12 pts who received at least 3 CYAD‐01 infusions in the dose‐escalation segment, 2 pts with MM did not have evidence of clinical response. For pts with r/r AML/MDS, 4/10 pts had overall response (OR) at D29 with 1 complete remission (CR) with partial hematologic recovery (CRh) for 16 months in a r/r AML pt at DL‐1, 2 CR with incomplete hematologic recovery (CRi) for 1 month in AML pts at DL‐1 and DL‐3, and 1 marrow CR (mCR) for 1 month in an MDS pt at DL‐3. 2 AML pts at DL‐2 had stable disease (SD) with bone marrow (BM) blast percentage decrease upon 1st treatment cycle and further reduction upon 2nd treatment cycle. Two other AML pts in DL‐3 achieved SD for at least 2 months. 2 AML pts did not show evidence of clinical response.DEPLETHINK study: 6 pts were enrolled in the first 2 cohorts which evaluated 1x108 cells/inf. In total, there were 3 G3/4 treatment‐related AE observed in the same pt. Five CRS occurred in 4 pts: 3 G1/2 after the 1st infusion and 2 CRS during 2nd cycle (1 G4 CRS and 1 G1), which resolved with tocilizumab treatment. At the 1st cohort, 2 pts reached a stable disease (SD) at D36, allowing the initiation of the 2nd cycle of 3 CYAD‐01 infusions.Summary/Conclusion:Altogether, results obtained to date in both phase 1 trials demonstrate the safety of CYAD‐01 with or without preconditioning chemotherapy in patients with r/r hematological malignancies. A promising OR rate of 40% at D29 was seen in pts with r/r AML/MDS in the THINK study. The DEPLETHINK study is still accruing.image

Comparisons of the outcomes between early and late tocilizumab treatment in systemic juvenile idiopathic arthritis.

Around 40% of systemic juvenile idiopathic arthritis (SJIA) in Thailand is steroid dependent or fails to respond to conventional therapy; therefore, tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody, was indicated in these patients. Due to financial problems, some patients cannot receive TCZ treatment immediately following failure of the conventional treatment occurs, leading to disability and poor quality of life. Therefore, this study focused on the outcomes between early and late TCZ treatment in SJIA patients. This was an observational study. Baseline characteristics and disease severity were collected. Patients were divided into the early TCZ treatment group and the late TCZ treatment group. The outcomes of this study were the remission rates by the end of the study and treatment response using the American College of Rheumatology Pediatric (ACR Pedi) 30, 50, 70 criteria at 3, 6, 9, and 12months after TCZ initiation. Descriptive analyses were conducted to determine the outcomes. Twenty-three SJIA patients were included in this study. At the end of this study, patients in the early TCZ treatment had a remission rate of 54.5%, whereas none in the late TCZ treatment achieved remission. At the 12-month follow-up, 10 patients (91%) in the early TCZ treatment group and 6 patients (50%) in the late TCZ achieved ACR Pedi 70. The outcomes of TCZ treatment in SJIA patients depend on the time to start TCZ treatment. In the early TCZ treatment, SJIA patients had a higher remission rate and better treatment response than patients who received TCZ treatment late.

Very early improvements in the wrist and hand assessed by power doppler sonography predicting later favorable responses in tocilizumab‐treated patients with rheumatoid arthritis

To investigate the response of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) by ultrasonographic evaluation of changes in the wrist and hand, and to determine whether such assessments during early TCZ treatment predict later clinical outcome. Thirty-two RA patients about to receive TCZ treatment were examined by ultrasound at baseline and after 2 weeks using the Outcome Measures in Rheumatology Clinical Trials semiquantitative scoring of 22 joints (both wrists, proximal interphalangeal joints 1-5, and metacarpophalangeal joints 1-5) as well as clinical and laboratory variables, leading to a calculation of composite indexes. The aim was to determine whether methotrexate treatment and clinical, laboratory, and ultrasonographic evaluation after 2 weeks of TCZ treatment predict treatment outcome at 24 weeks, as assessed by the Disease Activity Score in 28 joints (DAS28). Changes of ultrasound scores after 2 weeks were found to be correlated with changes in DAS28 at 24 weeks (r = 0.545-0.622, P < 0.05). The change of sum power Doppler scores after 2 weeks of treatment was identified as the variable most closely correlated with the change in DAS28 at 24 weeks (r = 0.622, P < 0.05). The best predictors after 2 weeks of favorable treatment outcome at 24 weeks were improved power Doppler scores. Methotrexate treatment and composite indexes did not predict favorable treatment outcome in this study.