Optimising alemtuzumab therapy for refractory B cell chronic lymphocytic leukaemia (CLL)

Abstract

6522 Background: Approximately half of CLL patients do not respond to alemtuzumab and others progress after responding to alemtuzumab. We report here factors predictive for lack of response and approaches to achieve the best outcome for these patients. Methods: 91 patients with relapsed or refractory CLL received alemtuzumab aiming for minimal residual disease (MRD) negativity. Factors correlated with response were reviewed and strategies for overcoming resistance or relapse are reported. Results: The chance of response was associated with lymph node size (p <0.0001): High dose methyl prednisolone (HDMP; 1g/m2/day x5 every 4 weeks; 4 patients) or CHOP (1) were used to reduce bulky nodes prior to alemtuzumab. 2 of 5 had a resolution of lymph nodes with both achieving MRD negative remissions with alemtuzumab. The other 3 did not respond to HDMP or alemtuzumab. 8 patients refractory to alemtuzumab, due to bulky lymph nodes, received alemtuzumab with concurrent fludarabine and 6 responded (2 MRD negative, 2 CR, 2 PR). In addition, 9 patients relapsing after a median of 23 months (range 8–46) from alemtuzumab were retreated of which 5 responded (1 MRD negative, 2 CR, 2 PR): 2 of the non-responders then received alemtuzumab combined with fludarabine with 1 achieving MRD negativity. One patient was treated on relapse directly with the alemtuzumab/fludarabine combination and achieved a MRD negative CR. Thus 11 refractory patients received combined alemtuzumab and fludarabine with 8 responding (4 MRD negative, 2 CR, 2 PR). Conclusions: Gross lymphadenopathy predicts for poor response to alemtuzumab but therapy with HDMP or CHOP followed by alemtuzumab can be effective in achieving MRD negative CR. The majority of alemtuzumab refractory patients (8/11) respond to the addition of fludarabine. Retreatment with alemtuzumab was effective for 3 of 7 relapsing patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ilex Oncology Ltd. Ilex Oncology Ltd. Ilex Oncology Ltd.