Phase II study of alemtuzumab–rituximab therapy in previously untreated patients with chronic lymphocytic leukemia: short- and long-term outcomes

Abstract

We investigated the safety, efficacy, and long-term outcomes of alemtuzumab and rituximab (AR) combination therapy in previously untreated patients with CLL. Thirty patients, ages 28-80 years, 47% older than 60 years, 90% Rai clinical stages II-IV, and 67% without favorable cytogenetics received AR. Based on the NCI-WG 1996 criteria, OR was 100%, with 60% CR. With CT scans OR was 70%, with 23% CR, 47% PR, and 30% SD. Sixty-seven percent of patients showed no evidence of MRD in the bone marrow by 6-color flow cytometry. Median PFS, TFS, and 5-year OS were 24.4, 50.7 months, and 80%, respectively. Grade 3/4 neutropenia and thrombocytopenia were reported in 30% and 7% of patients, respectively. CMV reactivation, asymptomatic in all but one patient, occurred in 8 patients. Immunotherapy with alemtuzumab and rituximab results in robust responses and long asymptomatic therapy-free intervals. It is well tolerated with infrequent, predictable, and easily managed complications.

Early treatment of high risk chronic lymphocytic leukemia with alemtuzumab, rituximab and poly-(1-6)-beta-glucotriosyl-(1-3)- beta-glucopyranose beta-glucan is well tolerated and achieves high complete remission rates

“…However, monotherapy therapy with either rituximab or alemtuzumab rarely achieves a complete or sustained response and is not curative. Combination therapy with alemtuzumab and rituximab is effective and tolerable resulting in high complete response rates in phase II studies [1-5]. Although these response rates appear to be better than those reported previously for monotherapy with either mAb [1-5], there are no reported randomized studies comparing therapy with alemtuzumab alone with the combination of alemtuzumab and rituximab.…”

“…Combination therapy with alemtuzumab and rituximab is effective and tolerable resulting in high complete response rates in phase II studies [1-5]. Although these response rates appear to be better than those reported previously for monotherapy with either mAb [1-5], there are no reported randomized studies comparing therapy with alemtuzumab alone with the combination of alemtuzumab and rituximab. In addition, the outcomes for both of these regimens are suboptimal, and even patients who achieve a complete response (CR) to therapy have a relatively short duration of response.…”

Flow cytometric evaluation of measurable residual disease in chronic lymphocytic leukemia: Where do we stand?

“…Despite this, great attention has been paid on MRD evaluation due to the demonstration of the relevant prognostic impact of undetectable (u)‐MRD in immuno‐chemotherapy and venetoclax plus CD20‐antibody combinations (Table 1). 1–23 Furthermore, the detection of u‐MRD status before discontinuation therapy is crucial when targeted agents, such as B cell receptor (BCR) inhibitors, are used 24–26 . Actually, the advent of BCR inhibitors initially reduced the relevance of MRD measurements, because these drugs as single agents aim more at the control rather than at the eradication of the disease itself.…”

A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG‐ACRIN cancer research group (E1908)

“…Combination therapy with alemtuzumab and rituximab achieved high response rates in phase II studies [6–10]. Although these response rates are higher than those previously reported for monotherapy with either mAb [6–11], there are no reported randomized studies showing conclusively that the addition of rituximab to alemtuzumab therapy in CLL patients improves outcome.…”