title: Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma.
abstract: A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Tomblyn
authors.affiliation: Helen F Graham Cancer Center, Newark, DE.
authors.forename: Jamal G
authors.initials: JG
authors.lastname: Misleh
authors.affiliation: Indiana University Health Center for Cancer Care, Goshen, IN.
authors.forename: Ebenezer A
authors.initials: EA
authors.lastname: Kio
authors.affiliation: Immunomedics, Morris Plains, NJ.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.affiliation: Immunomedics, Morris Plains, NJ.
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.affiliation: Immunomedics, Morris Plains, NJ Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA dmg.gscancer@att.net.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D016499:Radioimmunotherapy; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes; C448700:epratuzumab; C493846:veltuzumab