A Phase I Study Of Myeloablative Radioimmunotherapy Using Iodine-131 Anti-CD45 Antibody Followed By Autologous Stem Cell Transplantation For High-Risk B-Cell and T-Cell Non-Hodgkin Lymphoma and Hodgkin Lymphoma

摘要: Background High-dose therapy and autologous stem cell transplant (ASCT) remains the standard of care for many high-risk/relapsed B-cell non-Hodgkin lymphomas (B-NHL), T-cell NHL (T-NHL) classical Hodgkin lymphoma (HL), yet most will not achieve sustained remissions. anti-CD20 radioimmunotherapy (RIT) ASCT has been successfully employed to address this challenge in B-NHL, relapse still occurs potentially due blockade target sites by circulating rituximab (R). RIT options are limited patients with T-NHL HL. Preclinical data indicate that targeting panhematopoietic antigen CD45 can circumvent R blocking B-NHL a variety histologies (Gopal, 2008 & 2009). We thus performed phase I trial using high-dose anti-CD45 T-NHL, HL. Methods Patients were ≥18 years old relapsed, refractory, or high-risk HL had acceptable organ function an ECOG performance status 0-1 no detectible human anti-mouse antibodies. They could have received ≥20 Gy prior radiation (RT) critical organs within 1 year, allogeneic at any time. All first antibody (BC8) trace-labeled 131I followed gamma camera imaging evaluate biodistribution estimate organ-specific absorbed doses. then 131I-BC8 dose determined following: RT >20 started 10 dose-limiting normal (Arm A), while others escalation 20 B). Subsequent escalation/de-escalation two-stage approach (Storer, 2001). occurred after sufficient decay, G-CSF was on day 1. Dose limiting toxicity (DLT) Bearman grade III/IV events. The primary objective maximum tolerated dose, defined as yielding DLT rate 25%. Responses scored criteria (Cheson, 2007). Results Between August 2009 March 2013, 15 treated. Median age 62 (range 20-71); stage = 11 (73%); median regimens 3 2-12), including ASCT; chemorefractory disease (i.e., 500/μl) platelet (>20 K/μl) engraftment 8 10-20) 12 8-26) days ASCT, respectively. No DLTs, non-relapse deaths, non-hematologic toxicities > NCI-CTCAE v3 observed. Currently, (73%) alive 7 (47%) progression-free follow-up months. Seven (54%) 13 measurable enrollment responses, 6 HL, follicular (FL; see [Table][1]). View table: Table Patient characteristics, escalation, response. Conclusion Myeloablative doses targeted safe feasible lymphoma, DLTs observed delivery up 30 liver. Objective responses heavily-treated This work led current studies yttrium-90 therapeutic radionuclide (given its longer beta pathlength absence emission) lymphoma. Disclosures: relevant conflicts interest declare. [1]: #T1