Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias Conference Paper

Authors: Jurcic, J. G.; Caron, P. C.; Nikula, T. K.; Papadopoulos, E. B.; Finn, R. D.; Gansow, O. A.; Miller, W. H. Jr; Geerlings, M. W.; Warrell, R. P. Jr; Larson, S. M.; Scheinberg, D. A.
Title: Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias
Conference Title: 5th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer
Abstract: M195, a mouse monoclonal antibody reactive with the early myeloid antigen CD33, has been shown to target leukemia cells in patients and to reduce large leukemic burdens when labeled with 131I. A complementarity-determining region-grafted, humanized version (HuM195) has demonstrated similar targeting of leukemia cells without immunogenicity. We have studied two applications of therapy with 131I-M195. First, to intensify therapy prior to bone marrow transplantation (BMT), we combined 131I-M195 with busulfan and cyclophosphamide. Fifteen patients received first BMT for relapsed or refractory acute myelogenous leukemia or accelerated or blastic chronic myelogenous leukemia; four received second BMT for relapsed chronic or accelerated chronic myelogenous leukemia. Doses of 131I-M195 ranged from 120 to 230 mCi/m2. Few toxicities could be attributed to 131I-M195 therapy, and all patients engrafted. Eighteen patients achieved complete remission. Among those patients receiving first BMT, three have remained in unmaintained remission for 18+ to 29+ months. Six patients relapsed, including one with isolated central nervous system disease 32 months after BMT. Ten patients died in complete remission of transplant-related complications. Second, we studied whether 131I-M195 could reduce minimal residual disease and prolong remission and survival durations safely in patients with relapsed acute promyelocytic leukemia after they attained remission with all-frans-retinoic acid. Seven patients were treated with either 50 or 70 mCi/m2 131I-M195. Toxicity was limited to myelosuppression. As a measure of minimal residual disease, we monitored PML/RAR-α mRNA by reverse transcription PCR. Six patients had positive reverse transcription PCR assays prior to receiving 131I-M195; two converted transiently to negative. Median disease-free survival and overall survival of the seven patients were 8 (range, 3-14.5) months and 28 (range, 5.5-43+) months, respectively. This regimen compares favorably with others for relapsed acute promyelocytic leukemia. In an effort to avoid nonspecific cytotoxicity associated with 131I in future trials for minimal residual disease, we have conjugated short-range, α particle-emitting radioisotopes to HuM195 using a bifunctional chelate, 2-(p-isothiocyanatobenzyl)-cyclohexyldiethyl-enetriaminepentaacetic acid, with high efficiency and specific activities. 212Bi-HuM195 has demonstrated dose- and specific activity-dependent killing of HL60 cells in vitro. Injection of 213Bi-HuM195 into healthy BALB/c mice produced no effects on weight or viability.
Keywords: adult; cancer survival; clinical article; treatment outcome; disease-free survival; unclassified drug; cancer recurrence; dose response; drug efficacy; conference paper; animal; mice; tumor localization; chronic myeloid leukemia; monoclonal antibody; cancer regression; antibodies, monoclonal; iodine radioisotopes; leukemia, myeloid; acute myeloblastic leukemia; antibody specificity; antigens, cd; immunosuppressive treatment; radioimmunotherapy; bone marrow transplantation; radioisotope therapy; antigens, differentiation, myelomonocytic; middle age; bismuth 213; monoclonal antibody m 195; monoclonal antibody hum195; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; monoclonal antibody hum195 bi 213; monoclonal antibody i 131; monoclonal antibody m195 i 131
Journal Title Cancer Research
Volume: 55
Issue: 23 Suppl.
Conference Dates: 1994 Oct 6-8
Conference Location: Princeton, NJ
ISBN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1995-12-01
Start Page: 5908s
End Page: 5910s
Language: English
PUBMED: 7493368
PROVIDER: scopus
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus