Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M195 Journal Article

Authors: Jurcic, J. G.; Caron, P. C.; Miller, W. H. Jr; Yao, T. J.; Maslak, P.; Finn, R. D.; Larson, S. M.; Warrell, R. P. Jr; Scheinberg, D. A.
Article Title: Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M195
Abstract: Acute promyelocytic leukemia (APL) provides a model to examine the sequential use of selective oncogene product-targeted and lineage-targeted agents. All-trans retinoic acid (RA) has been shown to produce brief remissions by a novel differentiating mechanism in most patients with APL. M195, a mouse monoclonal antibody (moAb) reactive with the cell-surface antigen CD33, can target myeloid leukemia cells in patients and reduce large leukemic burdens when labeled with 131I. We studied whether 131I-M195 could safely reduce minimal residual disease and prolong remission and survival durations in patients with relapsed APL after they had attained remission with all-trans RA. Seven patients with relapsed APL in second remission were treated with either 70 (n = 2) or 50 (n = 5) mCi/m2 of 131I-M195. As a measure of minimal residual disease, we serially monitored PML/RAR-α mRNA by a reverse transcription polymerase chain reaction (RT-PCR) assay. There was no immediate toxicity. Late toxicity was limited to myelosuppression, but no episodes of febrile neutropenia were seen. Six patients had detectable PML/RAR-α mRNA after all-trans RA therapy; two had single negative RT-PCR determinations following 131I-M195. Median disease-free survival of the seven patients was 8 months (range 3-14.5). Four patients with median follow-up of 24 months remain alive, and median overall survival exceeds 21+ months (range 5.5-33+). This regimen based on targeted therapy compares favorably to other approaches for the treatment of relapsed APL, including that used in the immediately preceding trial in which patients were induced into remission and maintained with all-trans RA, as well as other chemotherapy-based regimens. These data support further study of moAb-based therapy for minimal residual disease in acute leukemia.
Keywords: survival; adult; clinical article; aged; clinical trial; neutropenia; cytarabine; follow up; reverse transcription polymerase chain reaction; bone marrow suppression; cell differentiation; monoclonal antibody; membrane antigen; iodine 131; drug mechanism; isotope labeling; messenger rna; daunorubicin; acute myeloblastic leukemia; idarubicin; retinoic acid; intravenous drug administration; oral drug administration; leukemia remission; retinoic acid receptor; apl; atra; monoclonal antibody m 195; human; male; female; priority journal; article; m195 moab
Journal Title: Leukemia
Volume: 9
Issue: 2
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 1995-02-01
Start Page: 244
End Page: 248
Language: English
PUBMED: 7869759
PROVIDER: scopus
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus