Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence

Abstract

Background Monoclonal antibodies may be used more effectively in combination. A previous study of intravenous (iv) bolus alemtuzumab plus rituximab in patients with chronic lymphocytic leukemia (CLL) recurrence produced a response rate of 54% after a 4-week treatment period. Methods To optimize dose, schedule, and route of alemtuzumab, a study was designed exploring continuous intravenous infusion (civ) followed by subcutaneous (sc) alemtuzumab together with weekly iv rituximab in patients with previously treated CLL. Results Data from 40 patients with a median age of 59 years, and a median of 3 prior regimens (range, 1-8 regimens) were evaluable. Approximately 64% of patients were fludarabine-refractory. Seven patients (18%) achieved a complete response (CR), 4 (10%) a nodular partial response (nPR), and 10 (25%) a partial response for an overall response rate of 53%. Of 11 major responses (CR, nPR), 8 occurred after cycle 1. Response rates were highest in blood (94%), followed by liver/spleen (82%), bone marrow (68%), and lymph nodes (51%). The combination did not generate unexpected toxicities. Cytomegalovirus (CMV) reactivations occurred in 6 patients (15%) and responded well to anti-CMV therapy. High titers of anti-idiotype antibodies after sc alemtuzumab were demonstrated in 1 patient, but remained without clinical sequelae. Conclusions The combination of civ/sc alemtuzumab plus rituximab has activity in some patients with recurrent/ refractory CLL and maximum response is achieved after 1 cycle (4 weeks) in 73% of patients. Further exploration in other settings of CLL together with accompanying pharmacokinetic studies is recommended.

Treatment of older patients with chronic lymphocytic leukemia: key questions and current answers

“…Nonchemotherapy regimens such as alemtuzumab-rituximab, [93][94][95] lenalidomide monotherapy, 96 lenalidomide in combination with rituximab, 97 rituximab monotherapy, 98 rituximab-GM-CSF, 99 and high-dose methylprednisolone Ϯ rituximab 100 have also been explored in clinical trials. With the exception of the alemtuzumabrituximab regimen for patients with nonbulky disease and/or del(17p13) and the methylprednisolone-rituximab regimen, there are currently inadequate data to recommend the routine use of these regimens.…”

Emerging antibody combinations in oncology

“…Phase 1/2 studies in hematological malignancies with rituximab in combination with either epratuzumab, galiximab or alemtuzumab, which target the B-cell antigens CD22, CD80 and CD52, respectively, demonstrated that these combinations were well-tolerated and resulted in clinical responses equal to or greater than single-agent therapy alone ( Table 2). [168][169][170][171] Preclinical evidence for expanded hematological indications for the combination of anti-CD20 and anti-CD52 mAbs have been reported and may influence further development of this combination, 172,173 although issues with adventitious infections may complicate its use as consolidation therapy. 174,175 A Phase 2b study testing the combination of rituximab and lumiliximab, which targets the B-cell marker CD23, did not achieve clinical superiority even though there were favorable signals in earlier trials.…”

Refractory chronic lymphocytic leukemia - new therapeutic strategies

“…The most adverse events were again infusion-related and well manageable. Infections were seen in 28 % of the patients; 15 % of the patients developed CMF infections which were only detected in blood samples without organ manifestation [16].…”