Publication Date:
2015-12-03
Description:
Background The current standard immunochemotherapy for frontline treatment of CLL is highly effective but has poor tolerance in older patients with comorbidities, potential long-term marrow toxicity, and limited efficacy in high risk CLL. Monoclonal antibody combination may offer an alternative, non-stem cell toxic treatment option. Here we update the safety and effectiveness of alemtuzumab-ofatumumab (A+O) combination as a frontline treatment for CLL. Methods This phase 2 study is conducted at Northwestern University and Karolinska University Hospital with an accrual goal of 60 patients. Eligibility requires symptomatic, previously untreated CLL, and PS ≤ 2. Alemtuzumab (Alem) is given subcutaneously tiw for up to 18 weeks (dose escalation 3mg-10mg-30mg for week 1 and 30mg per dose for subsequent weeks). Starting week 3, ofatumumab (Ofa) is added intravenously q2 weeks up to 8 doses at 300mg for dose 1 and 2000mg for doses 2-8. All patients received anti-herpes, anti-fungal and anti-pneumocystis prophylaxis. Cytomegalovirus (CMV) was monitored by PCR every other week. Bone-marrow biopsy and CT scans are required for response assessment (IWCLL 2008 criteria). Minimal residual disease (MRD) in bone marrow was assessed using 6-color flow. Hematologic toxicity was assessed using IWCLL 2008 criteria and non-hematologic toxicity graded by CTCAE 4.0. Results By June 22, 2015 the study has enrolled 52 patients among whom 47 patients have completed treatment and the updated efficacy reported here. Median age was 64 (range 45-79) years; 59% had Rai stage III/IV; 48% had unmutated IgHV, and 30% had high-risk cytogenetics with 11q-, 17p- and/or TP53 mutation. One early patient developed prolonged cytopenia after 18 weeks of therapy and died of sepsis; post-therapy bone marrow (BM) biopsy showed hypocellular marrow with no residual CLL (MRD negative). It was speculated that continued treatment with Alem beyond the point of MRD-negative CR in bone marrow might increase the risk of prolonged cytopenia. Early stopping rules were therefore implemented based on BM biopsy after 9 and 12 weeks of treatment. Alem is stopped if CR in the bone-marrow is achieved, or if cellularity
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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