Precision Medicine in Lymphoma by Innovative Instrumental Platforms

Paolo, Antonello Di; Arrigoni, E.; Luci, Giacomo; Cucchiara, Federico; Danesi, Romano; Galimberti, Sara

doi:10.3389/fonc.2019.01417

Cited by 13 publications

(9 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This important issue of no marker cases might be managed in future trials by increasing the number of translocation cluster regions 30 or by moving to high throughput technology, which, however, have only offered very preliminary data in FL so far. [31][32][33][34][35] As a second limitation, we acknowledge that a better assessment of a nonlifesaving therapy such as RM should integrate the evaluation of efficacy, safety, and patientreported outcomes including quality of life that was lacking in our trial. Moreover, we also acknowledge that, as frequently observed in pure academic trials, there is a tendency to under-report safety events.…”

Section: Discussionmentioning

confidence: 99%

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study

Luminari

Manni

Galimberti

et al. 2022

JCO

Self Cite

View full text Add to dashboard Cite

PURPOSE We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard vs experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively ( P = .238). CONCLUSION A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.

show abstract

Section: Discussionmentioning

confidence: 99%

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study

Luminari

Manni

Galimberti

et al. 2022

JCO

Self Cite

View full text Add to dashboard Cite

show abstract

“…In recent years, pharmacogenetic analyses have taken advantage of the employ of unsupervised techniques, as well as microarrays, GWAS, and next-generation sequencing platforms, which enable the screening of numerous possible genetic markers at the same time ( Di Paolo et al, 2019 ). In some cases, genetic markers were combined with clinical and laboratory characteristics to obtain highly performant predictive models ( Dubinsky et al, 2010 ).…”

Section: Personalized Medicine In Inflammatory Bowel Diseasesmentioning

confidence: 99%

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

Paolo

Luci

2021

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.

show abstract

“…It is expected that in 2030, 21 million people worldwide will suffer from cancer [ 2 ]. Tremendous progress, however, has been made in the treatment of individual cancers [ 3 , 4 , 5 , 6 ]. This is due, on one hand, to improved early detection and prophylaxis and, on the other, to the development of highly efficient drugs in a wide range of different substance classes.…”

Section: Introductionmentioning

confidence: 99%

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

et al. 2020

View full text Add to dashboard Cite

The combination of the “correct” triterpenoid, the “correct” spacer and rhodamine B (RhoB) seems to be decisive for the ability of the conjugate to accumulate in mitochondria. So far, several triterpenoid rhodamine B conjugates have been prepared and screened for their cytotoxic activity. To obtain cytotoxic compounds with EC50 values in a low nano-molar range combined with good tumor/non-tumor selectivity, the Rho B unit has to be attached via an amine spacer to the terpenoid skeleton. To avoid spirolactamization, secondary amines have to be used. First results indicate that a homopiperazinyl spacer is superior to a piperazinyl spacer. Hybrids derived from maslinic acid or tormentic acid are superior to those from oleanolic, ursolic, glycyrrhetinic or euscaphic acid. Thus, a tormentic acid-derived RhoB conjugate 32, holding a homopiperazinyl spacer can be regarded, at present, as the most promising candidate for further biological studies.

show abstract

Precision Medicine in Lymphoma by Innovative Instrumental Platforms

Cited by 13 publications

References 93 publications

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

Contact Info

Product

Resources

About