Abstract

Lumiliximab is a PRIMATIZED® anti-CD23 monoclonal antibody with human IgG1 constant regions and macaque variable regions. Preclinical data demonstrated that lumiliximab enhanced both fludarabine- and rituximab- mediated apoptosis in CLL cells. Thus, a Phase 1/2, open-label, dose-escalation, multicenter study (Study 152–30) evaluating lumiliximab + fludarabine, cyclophosphamide, and rituximab (L + FCR) for relapsed CD23+ B-cell CLL was initiated. Treatment has been completed and follow-up is ongoing. Thirty-one patients (pts) received either 375 mg/m2 (n=3) or 500 mg/m2 (n=28) of lumiliximab in combination with a 28-day cycle of FCR for up to 6 cycles. Median age at study entry was 58 yrs. The majority of pts (74%) were Rai Stage I/II. The most common adverse events included nausea (77%), pyrexia (61%), chills (55%), neutropenia (55%), and fatigue (48%). Twenty pts (65%) experienced a Grade 3 or 4 event. An overall response rate of 71% was demonstrated: 48% complete response (CR), 10% partial response (PR), and 13% unconfirmed PR. Currently, baseline cytogenetic data is available for 21 pts who received 500 mg/m2 of lumiliximab. Although preliminary, 1 of the 4 pts with del(17p13.1) responded; of the 6 pts with del(11q22.3), 5 responded with 4 attaining a CR. A comparison with published data from a study of FCR alone in 177 pts with relapsed or refractory CLL conducted at the M.D. Anderson Cancer Center (MDACC) (

Wierda W, O’Brien S, Wen S, et al.
J Clin Oncol.
2005
;
23
:
4070
–4078
) demonstrated that L + FCR has an acceptable safety profile, does not appear to increase the toxicity (including myelosuppression) of the FCR regimen, and compares favorably with the CR rate of the FCR regimen alone, as displayed in Table 1. Most pt characteristics (age, gender, median number of prior therapies, and WHO performance status) were similar between the 2 studies; however, more pts in the MDACC study were Rai Stage III-IV (50% vs 22%) and were rituximab-naïve (88% vs 40%). Furthermore, there were no obvious differences in hematologic toxicity between the 2 studies and the tolerability of L + FCR was similar to that of FCR, with approximately 50% percent of pts completing 6 cycles of treatment in both studies. These data suggest that L + FCR may produce a higher complete response rate than FCR without additional toxicity. Based upon this data, a multicenter, global, randomized study of L + FCR vs. FCR alone is being initiated.

Table 1.

Comparison of Responses in Study 152–30 and the MDACC Study

Study 152–30, L + FCR (N=31), n (%)MDACC, FCR (N =177), n (%)
1CR and PR response criteria were the same in both studies. 2PRu is included in the OR. 
Overall Response 22 (71%) 130 (73%) 
Complete Response1 15 (48%) 45 (25%) 
Partial Response1 3 (10%) 85 (48%) 
Unconfirmed Partial Response2 4 (13%)  
Study 152–30, L + FCR (N=31), n (%)MDACC, FCR (N =177), n (%)
1CR and PR response criteria were the same in both studies. 2PRu is included in the OR. 
Overall Response 22 (71%) 130 (73%) 
Complete Response1 15 (48%) 45 (25%) 
Partial Response1 3 (10%) 85 (48%) 
Unconfirmed Partial Response2 4 (13%)  

Disclosures: Kheoh, Wynne, & Molina employed by Biogen Idec.; Kheoh, Wynne, & Molina have Biogen Idec stock.; Kheoh, Wynne, & Molina have Biogen Idec stock options.; Byrd, Castro, O’Brien, Flinn, Forero-Torres, Kipps, Hereema, Lin.

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