The interval between frontline treatment and the second relapse (PFS2) predicts survival from the second relapse in follicular lymphoma patients

Mozas, Pablo; Sorigué, Marc; Rivas‐Delgado, Alfredo; Rivero, Andrea; Correa, Juan Gonzalo; Castillo, Carlos Armiñanzas; Nadeu, Ferran; Bataller, Àlex; Giné, Eva; Baumann, Tycho; Villamor, Neus; Campo, Elı́as; Magnano, Laura; Sancho, Juan‐Manuel; López‐Guillermo, Armando

doi:10.1111/ejh.13556

Cited by 2 publications

(2 citation statements)

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“…However, since its first description, other analyses have provided substantial nuance to this finding; replication studies have shown that the prognostic impact is of a smaller magnitude than initially reported, particularly in PETstaged patients [35] and that the poorest OS is likely restricted to primary refractory or very early relapsing (<6 or < 12 months) patients or to those with histological transformation [35][36][37]. The lack of association between POD24 and PFS2 in our study seems to indicate that POD24 is not always an ominous prognostic sign and that a substantial number of patients with POD24 can be rescued with subsequent lines of therapy, as suggested by a previous analysis [38]. However, patients with POD24, particularly primary refractory with an aggressive clinical course could have died before receiving the second line, and this would not be captured by second-line survival estimates.…”

Section: Resultssupporting

confidence: 51%

Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice

Rajamaki,

Sorigue,

Prusila

et al. 2024

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Background: The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. Patients and methods: We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1–2 FL between 1997 and 2016 in nine institutions were included. Results: The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7–9.3 years), 4.2 years (95% CI: 2.8–5.6 years) and 2.2 years (95% CI 1.7–2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. Interpretation: With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.

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Section: Resultssupporting

confidence: 51%

Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice

Rajamaki,

Sorigue,

Prusila

et al. 2024

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“…Preceding tumor tissue editing is known to impact consecutive therapies and therefore, determines therapy sequences (195). At best, tumor editing can even prolong progression-free survival, which may be translated in an overall survival benefit (128,179,191,196,197). During drug development, testing diversified systems status of tumor tissues for novel drug activities seems to be an important field for research to avoid missing significant drug activities in different tumor systems states.…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing by Tumor Tissue Editing

et al. 2022

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The combinatory use of drugs for systemic cancer therapy commonly aims at the direct elimination of tumor cells through induction of apoptosis. An alternative approach becomes the focus of attention if biological changes in tumor tissues following combinatory administration of regulatorily active drugs are considered as a therapeutic aim, e.g., differentiation, transdifferentiation induction, reconstitution of immunosurveillance, the use of alternative cell death mechanisms. Editing of the tumor tissue establishes new biological ‘hallmarks’ as a ‘pressure point’ to attenuate tumor growth. This may be achieved with repurposed, regulatorily active drug combinations, often simultaneously targeting different cell compartments of the tumor tissue. Moreover, tissue editing is paralleled by decisive functional changes in tumor tissues providing novel patterns of target sites for approved drugs. Thus, agents with poor activity in non-edited tissue may reveal new clinically meaningful outcomes. For tissue editing and targeting edited tissue novel requirements concerning drug selection and administration can be summarized according to available clinical and pre-clinical data. Monoactivity is no pre-requisite, but combinatory bio-regulatory activity. The regulatorily active dose may be far below the maximum tolerable dose, and besides inhibitory active drugs stimulatory drug activities may be integrated. Metronomic scheduling often seems to be of advantage. Novel preclinical approaches like functional assays testing drug combinations in tumor tissue are needed to select potential drugs for repurposing. The two-step drug repurposing procedure, namely establishing novel functional systems states in tumor tissues and consecutively providing novel target sites for approved drugs, facilitates the systematic identification of drug activities outside the scope of any original clinical drug approvals.

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The interval between frontline treatment and the second relapse (PFS2) predicts survival from the second relapse in follicular lymphoma patients

Cited by 2 publications

References 12 publications

Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice

Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice

Drug Repurposing by Tumor Tissue Editing

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