Campath Continuous IV Followed by Subcutaneous Campath+Rituximab

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[2827] The Combination of Alemtuzumab [Continuous Intravenous

Infusion (civ) Followed by Subcutaneous Injection (sc)] Plus

Rituximab Has Activity in Patients (pts) with Relapsed Chronic

Lymphocytic Leukemia (CLL). Session Type: Poster Session, Board #56-

III

Stefan Faderl, Alessandra Ferrajoli, G. Wierda,

O'Brien, Farhad Ravandi-Kashani, Fayad, Deborah , Hagop

Kantarjian, L. Browning, J. Keating Department of

Leukemia, The University of Texas MD Cancer Center, Houston,

TX, USA; Department of Lymphoma, The University of Texas MD

Cancer Center, Houston, TX, USA

Available data suggest enhanced activity of monoclonal antibodies in

combinations. In a previous study of iv bolus alemtuzumab plus

rituximab in relapsed CLL, we have shown that the combination is safe

and produces a response rate of 54% following a 4-week treatment

period (Blood 101: 3413, 2003).

As questions remain about the optimal dose, schedule and route of

administration of alemtuzumab, we have been exploring alemtuzumab by

civ followed by sc injections in combination with rituximab in pts

with relapsed/refractory CLL who express both CD20 and CD52.

Forty-five pts have been enrolled of whom 32 pts are evaluable (30

CLL, 1 CLL/SLL, 1 MZL). Six pts are too early and 7 are inevaluable

[withdrawal of consent prior to treatment start (2), ineligible (2),

removal from study and continuation of therapy with home physician

(3)].

All pts received alemtuzumab 15mg by civ over 24 hours daily x 6 days

on days 2-7 of the first course followed by 30mg sc twice weekly on

days 3 and 5 of weeks 2 to 4 (one course). Rituximab was given at

375mg/m2 iv on day 1 followed by 500mg/m2 on days 8, 15, and 22.

Maximum duration of therapy was 3 courses. Pts received standard

premedication with acetaminophen and an antihistamine, and

antiinfective prophylaxis with TMP/SMX and valacyclovir. CMV

antigenemia was tested before and after completion of each course.

The median age was 59 yrs (range 39-78), the median number of prior

therapies was 3 (1-8), and the median b2M 3.8 mg/dL (1.7-13.6).

Seventeen pts (53%) had Rai stage 3 disease. Eighteen pts (56%) were

refractory to fludarabine and alkylators. All pts had prior

rituximab; only 4 (13%) had received alemtuzumab.

Sixteen pts (50%) responded [8 CR (25%), 1 PRn (3%), 7 PR (23%)]

following one course. Response by site: peripheral blood 24/26 (92%),

marrow 22/32 (69%), lymph nodes 13/26 (50%) and liver/spleen 8/9 pts

(89%). The combination was well tolerated with no unexpected

toxicities.

Most non-hematologic AEs were infusion-related and grade 2 by NCI

toxicity criteria. Fevers and chills occurred in up to 56% of pts,

fatigue in 34%, skin rashes in 19%, nausea in 16%, myalgias in 9%,

and diarrhea in 6%.

Although toxicites were more frequent with civ alemtuzumab than

during the s.c. injections (with the exception of skin rashes), civ

alemtuzumab was well tolerated. CMV reactivation occurred in 7 pts

(22%) and was the most common infectious complication.

In conclusion, the combination of civ/sc alemtuzumab plus rituximab

has activity in patients with relapsed and refractory CLL. Most

responses occurred after 4 weeks of therapy only. The combination is

well tolerated. Side effects are predictable and manageable.