Alemtuzumab is highly effective at eliminating chronic lymphocytic leukemia (CLL) from bone marrow, the usual site of residual disease following treatment with a fludarabine-based regimen. Eradication of residual disease has been associated with longer time to progression and overall survival. A clinical trial was conducted to evaluate the activity of alemtuzumab 30mg SQ thrice weekly for 4 weeks each course (up to 2) to eliminate residual disease. Eligible pts were recently treated and achieved NCI-WG partial remission (PR) with measurable disease or complete remission (CR) with residual disease present in the bone marrow by 2-color flow cytometry. Responders on this trial were pts with NCI-WG PR that converted to CR or nodular PR, pts with nPR converted to CR, or pts in CR that had no evidence of disease by 2-color flow cytometry following treatment. To date, 29 pts have been enrolled and treated, 3 CR, 7 nPR, and 19 PR. The median number of prior treatments was 1 (range, 1–6); 2 PR pts were fludarabine-refractory. The median age=65(49–82) yrs; WBC=4.9(2.5–18.3)K/μ L; HGB=13.7(10.8–16.6)g/dL; PLT=186(93–418)K/μ L; ANC 2.4(.2–7.1)K/μ L; β 2M=1.7(1.3–3.5)mg/L. There were 12 / 23 ZAP70+; 13 / 23 with unmutated IgVH; all had PS 0–1. Twenty-three pts completed 1 and 6 completed 2 courses. There was 1 death (PR) due to uncontrolled hemolytic anemia and 1 pt was not assessable (CR) for response. Of the 27 assessable pts, there were 21 (78%) responders: 2 / 2 CR, 8 / 9 nPR, and 11 / 16 PR. The median follow-up time is 10 mo; 11 / 22 continue with their response, the median time to loss of response is 10 mo. Grade (G)3 and G4 neutropenia was experienced by 4 and 3 pts during treatment, respectively. Anemia, G3 was seen in 2 pts; only 1 pt experienced G4 thrombocytopenia. Therapy was well-tolerated; 25 / 29 pts developed G1–2 injection-site reactions. Twenty-five pts self-administered alemtuzumab without difficulties. No patients developed anti-alemtuzumab antibodies. Two pts received treatment for documented CMV reactivation, and 1 received empiric treatment for fever but was CMV negative by PCR. There were 4 pts with serious adverse events: 1 neutropenic gram positive bacteremia; 1 neutropenic fever without infection; 1 neutropenic pneumonia; 1 pt with pneumonia and fatal AIHA. On a previous trial with alemtuzumab IV for residual disease (

O’Brien et al.
Cancer
98
:
2657
,
2003
), the updated response rate for 58 pts is 53%; the median time to loss of response is 34 mo, 9 mo for pts who had minimal residual disease (MRD) at end of treatment by PCR for IgVH. Therefore the median time to loss of response is shorter in this trial, despite a higher response rate. Evaluation for MRD in bone marrow is ongoing to determine if the shorter time to loss of response can be attributed to more MRD, possibly suggesting that longer treatment time may be needed for more durable responses with SQ alemtuzumab administration.

Topics:
alemtuzumab, brachial plexus neuritis, residual tumor, self administration, neutropenia, flow cytometry, fludarabine, pneumonia, polymerase chain reaction, adverse event

Disclosures: Berlex Laboratories.

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2006, The American Society of Hematology
2006
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