BL22, een niet toxische aanpak, zorgt voor 19 complete en 6 gedeeltelijke remissies uit trial met 31 patienten met hairy cell leukemie. Artikel update 12 december 2012
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Complete remission to BL22 and hairy cell leukemia tumor burden
Abstract No: 2373 Citation: Proc Am Soc Clin Oncol 22: page 590, 2003 (abstr 2373)
Author(s): R. J. Kreitman, D. R. Squires, M. Stetler-Stevenson, P. Noel, K. Matsushita, D. J. P. Fitzgerald, W. H. Wilson, I. Pastan; NCI, Bethesda, MD; NHLBI, Bethesda, MD
Abstract: Hairy cell leukemia (HCL) cells that are cladribine resistant retain CD22. BL22, a recombinant immunotoxin targeting CD22, has finished phase I accrual in 31 patients with cladribine-resistant HCL. Patients received 151 cycles of BL22 at dose levels between 3 and 50 ug/kg every other day for 3 doses (QOD x3). There were 19 complete and 6 partial responders (61% CR, 19% PR). CR was observed after cycle 1 in 11 and after cycles 2-14 in 8 patients. The cycle 1 CR rate was related to BL22 dose level (p = 0.03) and area under the curve (AUC) (p = 0.012). Low (< 50/mm3) circulating HCL count was also associated with cycle 1 CR (p = 0.018) but not with dose level (p = 0.13), possibly because low HCL counts were associated with high AUC (p = 0.016). Of 6 non-responders, 5 had high tumor burden with either high HCL count (> 70,000/mm3) (n=2), abdominal mass > 10 cm (n=2), or spleen size > 25 cm (n=1), and 3 had high levels of neutralizing antibodies. However, some patients achieving CR also had high tumor burdens with HCL counts up to 132,000/mm3, spleen size up to 21 cm, and lymph nodes up to 2.5 cm. Of the 19 CRs, 1 had minimal residual disease (MRD) in the bone marrow biopsy by immunohistochemistry and 2 had MRD by flow cytometry of blood. Serum soluble CD25, a recognized HCL marker, normalized with CR in 11 out of 11 patients evaluated. Soluble CD22, previously unreported in human serum, was measured by ELISA at 120 +/- 40 (mean +/- standard deviation) ng/ml pretreatment (n=12), 0.6 +/- 4 ng/ml after CR (n=8, p < 0.001 vs pretreatment), and 4.8 +/- 1.2 ng/ml in normal donors (n=7, p < 0.001 vs pretreatment). Eight out of 19 CRs relapsed without cytopenias and 3 out of 3 who were retreated reentered CR with more BL22. All 3 with MRD relapsed. The median (range) CR duration has not been reached at 18 (3-38) months. We conclude that CR to BL22 is affected by tumor burden and that further testing will help optimize dosing and retreatment to further improve CR rates and durations.
