Abstract 4595: Moxetumomab pasudotox spares CD4 and CD8 lymphocytes in multiply relapsed hairy cell leukemia patients, while prospective trials of first, second, and later lines of purine analogs show increasing toxicity
Authors: Kreitman Robert J. , Stetler-Stevenson Maryalice , Arons Evgeny , Pastan Ira 
Published: July 2017

Abstract
The purine nucleoside analogs cladribine and pentostatin damage DNA and cause long-term suppression of CD4 and CD8 lymphocytes in patients with hairy cell leukemia (HCL). There is increasing concern that these reductions, particularly in CD4+ T-cells, may be associated with opportunistic infections and secondary malignancies. The anti-CD22 recombinant immunotoxin moxetumomab pasudotox targets HCL without damaging DNA, and spares T-cells. In a phase 1 trial, 20 patients treated with 50 ug/Kg every other day for 3 doses for 2-8 (median 4) cycles were evaluated for T-cell subsets. CD4 cells increased -56% to 152% (median 46%) after end of treatment, decreasing in only 1 of the 20 patients. Because there is very little prospective data on the effect of purine analogs on T-cells, we analyzed data from 80 consecutively enrolled patients receiving cladribine in first line, 40 receiving cladribine in second line, and 52 receiving either pentostatin or bendamustine in third or later lines. The latter group was most appropriate to compare with moxetumomab pasudotox, which was also used in third or later-line treatment of HCL. CD4 counts after moxetumomab pasudotox were 85-600 (median 424), compared to 22-618 (median 73) after third or later line purine analog (p&lt;0.0001). These CD4 counts after moxetumomab pasudotox were even higher than those after first line (86-954, median 259, p=0.0037) or second line (53-724, median 185, p&lt;0.0001) cladribine. CD4 counts after first line cladribine were higher than those after second line cladribine (p=0004), which in turn were higher than those after third or later line purine analogs (p&lt;0.0001). Even after 2 years, CD4 counts after third or later line purine analogs, 41-1004 (median 264), n=43, remained suppressed compared to 1st line cladribine, 191-1044 (median 392, n=68, p=0.0013). The percent decreases in CD4 counts after first line cladribine were significantly greater compared to those after moxetumomab pasudotox (median 63% decrease vs 46% increase, p&lt;0.0001). CD8 counts were also preserved after moxetumomab pasudotox, increasing by -32% to 198% (median 46%). Similar differences between moxetumomab pasudotox and purine analog groups were observed with respect to CD8-cell suppression. Opportunistic infections, neutropenic fevers, and other infectious complications were much more common after purine analogs than after moxetumomab pasudotox, particularly in later lines of therapy. These data provide a rationale for avoiding repeated cycles of purine analog for relapsed HCL, and support the use of non-chemotherapy approaches like moxetumomab pasudotox before repeated courses of purine analog are tried. (Supported in part by MedImmune and NCI, Intramural Program).
Citation Format: Robert J. Kreitman, Maryalice Stetler-Stevenson, Evgeny Arons, Ira Pastan. Moxetumomab pasudotox spares CD4 and CD8 lymphocytes in multiply relapsed hairy cell leukemia patients, while prospective trials of first, second, and later lines of purine analogs show increasing toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4595. doi:10.1158/1538-7445.AM2017-4595