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Prognostic Significance of PET/CT in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline Chemoimmunotherapy.

ABSTRACT: The role of positron emission tomography/computed tomography (PET/CT) in identifying Richter Syndrome (RS) is well established, while its impact on the survival of patients with chronic lymphocytic leukemia (CLL) has been less explored. The clinical characteristics and PET/CT data of 40 patients with a biopsy-proven CLL who required frontline chemoimmunotherapy, FCR (fludarabine, cyclophosphamide, rituximab) in 20 patients, BR (bendamustine, rituximab) in 20, were retrospectively analyzed. Standardized uptake volume (SUV_max) values ? 5 were observed more frequently in patients with deletion 11q (p = 0.006) and biopsies characterized by a rate of Ki67 positive cells ? 30% (p = 0.02). In the multivariate analysis, the presence of large and confluent PCs emerged as the only factor with a negative impact on progression-free survival (PFS), and overall survival (OS). Deletion 11q also revealed a significant and independent effect on PFS. SUV_max values ? 5 showed no statistical impact on PFS while in multivariate analysis, they revealed a significant adverse impact on OS (median survival probability not reached vs. 56 months; p = 0.002). Moreover, patients with higher SUV_max values more frequently developed Richter Syndrome (p = 0.015). Our results show that higher SUV_max values identify CLL patients with a pronounced rate of proliferating cells in the lymph-node compartment, inferior survival, and an increased risk of developing RS.

SUBMITTER: Porrazzo M

PROVIDER: S-EPMC7408608 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Prognostic Significance of PET/CT in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline Chemoimmunotherapy.

Porrazzo Marika M Nicolai Emanuele E Riminucci Mara M Vitale Candida C Coscia Marta M De Paoli Lorenzo L Rago Angela A Buscicchio Giulia G Maestrini Giacomo G Ligia Silvio S Di Prima Alessio A Corsi Alessandro A Caronna Roberto R Gaidano Gianluca G Mauro Francesca Romana FR

Cancers 20200703 7

The role of positron emission tomography/computed tomography (PET/CT) in identifying Richter Syndrome (RS) is well established, while its impact on the survival of patients with chronic lymphocytic leukemia (CLL) has been less explored. The clinical characteristics and PET/CT data of 40 patients with a biopsy-proven CLL who required frontline chemoimmunotherapy, FCR (fludarabine, cyclophosphamide, rituximab) in 20 patients, BR (bendamustine, rituximab) in 20, were retrospectively analyzed. Stand ...[more]

PMID: 32635175

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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.

Project description:BackgroundData regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.MethodsIn a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.ResultsA total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50). The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36). The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib-rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib-rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001).ConclusionsThe ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).

Dataset Information

Prognostic Significance of PET/CT in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline Chemoimmunotherapy.

Publications

Prognostic Significance of PET/CT in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline Chemoimmunotherapy.

Similar Datasets

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