Consolidation Therapy With Subcutaneous Alemtuzumab After Fludarabine and Rituximab Induction Therapy for Previously Untreated Chronic Lymphocytic Leukemia: Final Analysis of CALGB 10101

Abstract

A B S T R A C T PurposeTo determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia. Patients and MethodsPatients (n ϭ 102) received fludarabine 25 mg/m 2 intravenously days 1 to 5 and rituximab 50 mg/m 2 day 1, 325 mg/m 2 day 3, and 375 mg/m 2 day 5 of cycle 1 and then 375 mg/m 2 day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks. ResultsOverall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n ϭ 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab. ConclusionAlemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.

Treatment of Younger Patients with Chronic Lymphocytic Leukemia

“…While several of these studies have shown that alemtuzumab consolidation is efficacious in achieving an MRD-negative state and results in better clinical responses and response duration, it is important to recognize that this treatment can be associated with myelosuppression, opportunistic infections, and other complications, and that these may offset its clinical benefit. 30 Alemtuzumab should be administered within clinical trials and not before at least 6 months have passed from the last chemotherapy regimen.…”

The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy

“…In fact, very few studies have demonstrated a clear benefit from MRD eradication or consolidation therapy in CLL, 31,32 and some of the strategies tested, although effective, resulted in significant toxicity. [33][34][35] Thirdly, it could be argued that MRD assessment is simply a surrogate for evalution of other adverse prognostic markers since, for instance, patients with a 17p A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV, TP53, NOTCH1 and SF3B1 mutations.…”

Rituximab maintenance after first-line therapy with rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia

“…[7][8][9] In CLL, maintenance or consolidation therapies with different drugs, including interferon-a, 10,11 rituximab, [12][13][14][15][16][17][18] alemtuzumab, [19][20][21][22][23][24][25][26][27] or more recently lenalidomide, 28 have been evaluated. As with other B-cell malignancies, the use of rituximab maintenance after induction treatment suggests a benefit in sustaining the response duration in patients with CLL.…”