E-resources
-
Sallman, David A; Brayer, Jason B.; Poire, Xavier; Havelange, Violaine; Awada, Ahmad; Lewalle, Philippe; Odunsi, Kunle; Wang, Eunice S.; Lonez, Caroline; Lequertier, Thomas; Alcantar-Orozco, Erik; Braun, Nathalie; Flament, Anne; Moors, Ine; Kerre, Tessa
Blood, 11/2019, Volume: 134, Issue: Supplement_1Journal Article
CYAD-01 cells are engineered T-cells expressing a chimeric antigen receptor (CAR) based on the natural full-length human natural killer group 2D (NKG2D) receptor fused to the intracellular domain of CD3ζ. NKG2D receptor binds to 8 ligands (MICA/B, ULBP1-6) expressed by a large variety of malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The hematological arm of the Phase I THINK study (NCT03018405) evaluates the safety and clinical activity of multiple CYAD-01 infusions (inf) without any prior preconditioning chemotherapy in r/r AML, MDS and multiple myeloma (MM) patients (pts). Three dose levels (DL) were evaluated: 3x108, 1x109 and 3x109 T-cells/inf. The first cycle of the treatment consists of 3 CYAD-01 infusions every 2 weeks and a potential 2nd cycle of 3 CYAD-01 infusions every 2 weeks if the patient is not in progressive disease (PD) at the end of the 1st cycle. Additional cohorts evaluate DL2 and DL3 following a denser treatment schedule for the 1st cycle of treatment, with the first 3 CYAD-01 infusions administered every week. As of end of July 2019, 16 pts were enrolled in the dose-escalation segment of the hematological cohort with the initial schedule (CYAD-01 infusions every 2 weeks) for 1st cycle, now completed. In total (uncleaned database), 7 pts experienced grade (G) 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 7 pts with only 2 pts at DL2 who experienced G3 CRS and 1 pt who experienced G4 CRS at DL3 reported as a dose-limiting toxicity (DLT). All CRS AEs resolved with early tocilizumab treatment. No treatment-related neurotoxicity AEs have been observed. Out of the 10 AML/MDS pts who received at least 3 CYAD-01 infusions and were assessed for clinical activity, 4 showed overall response (OR) at Day 29 of which 1 complete remission (CR) with partial hematologic recovery (CRh) for > 21 months in a r/r AML pt at DL1, 2 CR with incomplete hematologic recovery (CRi) for 1 month in AML pt at DL1 and DL3, and 1 marrow CR (mCR) for 1 month in an MDS pt at DL3. 2 AML pts at DL2 had stable disease (SD) for ≥ 3 months with bone marrow (BM) blast percentage decrease. Two other AML pts in DL3 achieved SD for at least 2 months. 2 AML pts did not have evidence of clinical response. The 2 evaluable MM pts did not show evidence of clinical response. As of end of July 2019, 8 pts were enrolled in cohorts with the dense schedule (4 in DL2 and 4 in DL3). Recruitment at 3x109 T-cells/inf. is still ongoing and is expected to be completed by the time of presentation. At DL2 (uncleaned database), only 1 pt out of 4 experienced a study treatment-related G4 AE (infusion related reaction). The 3 other pts experienced G1 or 2 study treatment-related AEs, with 3 pts who experienced G1/2 CRS. One AML pt reached a stable disease at the Day 32 tumor evaluation. At DL3, 2 out of 4 currently enrolled pts experienced study treatment related G3 AE (CRS) after their first CYAD-01 infusion. One of these G3 CRS was reported as a dose-limiting toxicity. Altogether, results obtained to date demonstrate an encouraging safety and tolerability profile of CYAD-01 without preconditioning chemotherapy in pts with r/r hematological malignancies. Encouraging anti-leukemic activity was observed in 6 out of 13 (46%) evaluable r/r AML/MDS pts in the THINK study, presenting relevant decrease in BM blasts. Four objective responses (1 CRh, 2 CRi, 1 mCR) were observed with the initial schedule. At DL2, the denser schedule did not modify the safety profile while increasing the area under the curve of CYAD-01 peripheral blood levels, which could suggest a possible impact on clinical activity at DL3, results expected by the time of presentation. Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Awada:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Lilly: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EISAI: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genomic Health: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ispen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Leo Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Wang:Abbvie: Other: Advisory role; Kite: Other: Advisory role; Jazz: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Pfizer: Other: Advisory role, Speakers Bureau; Stemline: Other: Advisory role, Speakers Bureau; Daiichi: Other: Advisory role; Amgen: Other: Advisory role; Agios: Other: Advisory role. Lonez:Celyad: Employment. Lequertier:Celyad: Employment. Alcantar-Orozco:Celyad: Employment. Braun:Celyad: Employment. Flament:Celyad: Employment.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.