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Critical appraisal of the role of rituximab in the treatment of patients with previously untreated or treated chronic lymphocytic leukemia (CLL).

ABSTRACT: Patients with chronic lymphocytic leukemia (CLL) have benefited from the introduction of targeted therapy for leukemia. Rituximab (a chimeric murine-derived monoclonal antibody that targets CD20 on lymphocytes) was the first monoclonal antibody to affect the natural course of this disease. Several reports have shown modest single-agent activity in patients with CLL. However, the best results come from the combination of this agent with chemotherapy; a significant benefit has been seen with the use of fludarabine, cyclophosphamide, and rituximab (FCR). The addition of rituximab to chemotherapy boosted overall response rates, complete response rates and prolonged progression free survival. Recent data showed an overall survival benefit with FCR. Other combinations including bendamustine and rituximab appear more effective than bendamustine alone, while combining rituximab with other types of agents also appears to improve response rates. This type of relatively nontoxic regimen is being investigated in elderly patients who may not tolerate standard combination chemoimmunotherapies.

SUBMITTER: Al-Kali A

PROVIDER: S-EPMC3262335 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Critical appraisal of the role of rituximab in the treatment of patients with previously untreated or treated chronic lymphocytic leukemia (CLL).

Al-Kali Aref A Wierda William W Keating Michael M O'Brien Susan S

Journal of blood medicine 20100621

Patients with chronic lymphocytic leukemia (CLL) have benefited from the introduction of targeted therapy for leukemia. Rituximab (a chimeric murine-derived monoclonal antibody that targets CD20 on lymphocytes) was the first monoclonal antibody to affect the natural course of this disease. Several reports have shown modest single-agent activity in patients with CLL. However, the best results come from the combination of this agent with chemotherapy; a significant benefit has been seen with the u ...[more]

PMID: 22282690

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Project description:Purpose of reviewThere have been significant advances in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) over the past two decades. However, the intention of treatment remains control of the disease and delay of progression rather than a cure which remains largely elusive. Considering that CLL is mostly seen in older patients, there are multiple factors that play a role in the selection of CLL beyond the frontline treatment. Here, we review the concept of relapsed CLL, factors that predispose to relapse, and therapeutic options available to this patient population. We also review investigational therapies and provide a framework for selection of therapies in this setting.Recent findingsPlease check if the affiliations are presented correctly.Targeted therapies with continuous BTK inhibitors (BTKi) or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and have become the preferred standard of care treatment. The second-generation more selective BTK inhibitors (acalabrutinib and zanubrutinib) have shown improved safety profile compared to ibrutinib. However, resistance to the covalent BTK inhibitors may emerge and is commonly associated with mutations in BTK or other downstream enzymes. The novel non-covalent BTK inhibitors such as pirtobrutinib (Loxo-305) and nemtabrutinib (ARQ 531) are showing promising activities for relapsed CLL refractory to prior covalent BTKi. Other novel therapies such as chimeric antigen receptor (CAR) T cell therapy have also shown significant activities for relapsed and refractory CLL. Measurable residual disease (MRD) assessment has a growing importance in venetoclax-based limited-duration therapy and there is mounting evidence that MRD negativity improves outcomes. However, it remains to be seen if this will become an established clinically significant endpoint. Further, the optimal sequence of various treatment options remains to be determined. Patients with relapsed CLL now have more options for the treatment of the disease. The choice of therapy is best individualized especially in the absence of direct comparisons of targeted therapies, and the coming years will bring more data on the best sequence of use of the therapeutic agents.

Dataset Information

Critical appraisal of the role of rituximab in the treatment of patients with previously untreated or treated chronic lymphocytic leukemia (CLL).

Publications

Critical appraisal of the role of rituximab in the treatment of patients with previously untreated or treated chronic lymphocytic leukemia (CLL).

Similar Datasets

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