Long Term Results of BL22 (CAT-3888) in Multiply Relapsed Hairy Cell Leukemia.

Abstract 3442

Poster Board III-330

BL22 is a 63 kDa anti-CD22 recombinant immunotoxin containing truncated Pseudomonas exotoxin and variable domains from an anti-CD22 antibody. Patients with multiply relapsed/refractory hairy cell leukemia received BL22 and achieved 19 (61%) complete remissions (CRs) and 6 (19%) partial responses (PRs) in phase I testing, and 17 (47%) CRs plus 9 (25%) PRs in phase II testing (n=36), for overall response rates (ORR) of 72-81%. The average dose/cycle was the same for phase I and II (29 vs 33 ug/Kg x3). The dose for phase II was 40 ug/Kg x3 initially and 30 ug/Kg x3 for retreatment, but retreatment was held if patients had hematologic remission (HR, neutrophils ≥ 1500/mm³, Hgb ≥ 11 g/dL, and platelets ≥ 100,000/mm³) after cycle 1. Disease-free survival (DFS, CR duration) for phase II has not yet been reached at a median of 32 (range 4-62) months, with 12 (71%) of 17 CRs still ongoing. Considering all 36 CRs from phase I and II testing, median DFS was 33 (3-112) months with 15 (42%) of 36 CRs ongoing. Patients in CR usually underwent bone marrow biopsy every 6 months for 2 years and yearly thereafter, and after relapsing usually remained in HR. In fact, the median HR duration of these patients has not yet been reached at 42 (range 4-112) months, with 24 (67%) of the 36 patients remaining in HR or CR. Outcomes were better for those with pre-BL22 spleens measuring ≤ 200 mm in height than those with either prior splenectomy or spleens > 200 mm, in terms of CR (68% vs 34%, p=0.007), ORR 95% vs 48%, p=0.000003), and DFS (median 69+ vs 27 mo, p=0.002). In contrast, CR rates or DFS was not related to whether patients had <1 (n=28) or >1 (n=8) years of response to their last course of purine analog (p=0.5-0.75). Of 69 patients who received BL22, 8 (12%) had a completely reversible hemolytic uremic syndrome (HUS) and all maintained normal renal function after a median 80 (9-112) months of follow-up. We conclude that BL22 is highly active producing durable remissions in chemoresistant HCL, particularly in patients with limited disease burden. Testing is underway with a high-affinity version of BL22, called HA22 (CAT-8015).