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The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients.

ABSTRACT: The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum ?2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL-IPI score stratified Binet stage A patients into three subgroups with different outcome. Since the CLL-IPI was originally developed to predict survival, we next investigated the optimal cut-off score to predict TTFT in Binet stage A patients. Recursive partitioning analysis identified three subsets with scores of 0 (n = 139), 1 (n = 90), and???2(n = 108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (P?

SUBMITTER: Molica S

PROVIDER: S-EPMC5072993 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients.

Molica Stefano S Shanafelt Tait D TD Giannarelli Diana D Gentile Massimo M Mirabelli Rosanna R Cutrona Giovanna G Levato Luciano L Di Renzo Nicola N Di Raimondo Francesco F Musolino Caterina C Angrilli Francesco F Famà Angelo A Recchia Anna Grazia AG Chaffee Kari G KG Neri Antonino A Kay Neil E NE Ferrarini Manlio M Morabito Fortunato F

American journal of hematology 20160808 11

The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CL ...[more]

PMID: 27465919

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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

The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients.

Publications

The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients.

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