Anaplastic Large Cell Lymphoma
Conditions
Keywords
Anaplastic Large Cell Lymphoma, ALK, DUSP22, TP63, BV-CHP, Brentuximab vedotin, sALCL
Brief summary
Systemic Anaplastic Large Cell Lymphomas (sALCL) are rare lymphomas for which the cooperation in the collection of biological and clinical data is necessary to improve knowledge on the disease. The addition of a targeted therapy to chemotherapy recently showed to be effective compared to standard chemotherapy. First-line therapy brentuximab vedotin-CHP for sALCL was recently approved in Italy following the published 5-year data from the ECHELON-2 study. Correlations with biological parameters are missing. Within the framework of the FIL, Investigators will assess the clinical outcomes-specifically response rates, progression-free survival (PFS), safety-in a retrospective cohort of patients diagnosed with sALCL and treated frontline with BV-CHP in the real-life setting. These outcomes will be correlated with data derived from PET/CT imaging and lymph node biological samples. Furthermore, Investigators will collect lymph node samples of patients diagnosed with sALCL and treated with BV-CHP at FIL Centers. The study will investigate the prognostic relevance of known molecular alterations (e.g., DUSP22, TP63). Through whole-exome sequencing and transcriptomic profiling, recurrent genetic alterations will be explored, as well as the cell of origin and the tumor microenvironment of sALCL, with particular attention to cell-to-cell interactions. A machine learning model will be validated to identify DUSP22 rearrangements from hematoxylin&eosin (H&E)-stained slides. Finally, integrated analysis of omics and clinical data using AI will aim to uncover biological signatures predictive of treatment response.
Interventions
None listed
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years; * Histological diagnosis of sALCL (ALK positive and ALK negative); * Have received BV-CHP as front-line therapy in real life setting; * Availability of histological material of initial ALCLs diagnosis: a FFPE block from an excisional/incisional biopsy must be provided for patient enrollment. FNAB and GNAB will not be considered for the study; * Signed written informed consent
Exclusion criteria
* Histological diagnosis other than sALCL; * Front line treatment other than BV-CHP; * Patients treated with BV-CHP in the contest of a clinical trial; * Refuse to sign a written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the progression free survival (PFS) | From the beginning to the end of the study (up to 24 months) | Progression free survival (PFS) from the diagnosis of ALCL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate overall response rate (metabolic CR+PR) | From the beginning to the end of the study (up to 24 months) | Rate of overall response rate (ORR, CR+PR) |
| To evaluate the overall survival (OS) | From the beginning to the end of the study (up to 24 months) | Overall survival (OS) from diagnosis of lymphoma |
| To evaluate safety profile of the BV-CHP regimen | From the beginning to the end of the study (up to 24 months) | Incidence of any grade of adverse events (AEs) and of AEs with grade \>2 according to CTCAE v5 |
| To assess the prognostic role of interim PET scan in term of Progression Free Survival | From the beginning to the end of the study (up to 24 months) | PFS stratified according to interim PET result |
| To explore the role of ASCT consolidation in term of overall response rate | From the beginning to the end of the study (up to 24 months) | Rate of ORR and CR with and without ASCT consolidation |
| To assess the incidence of early and late relapses | From the beginning to the end of the study (up to 24 months) | Rate of POD24 (early and late first progression/relapse after induction treatment) |
| To assess the response rate to subsequent therapies including BV-retreatment | From the beginning to the end of the study (up to 24 months) | Rate of CR and ORR after subsequent therapies |
| To assess predictive factors of response rate | From the beginning to the end of the study (up to 24 months) | Investigate if one or more response rate predictive factors could be identify among clinical data, biological data (presence of ALK, DUSP22, TP63 alterations, mutational landscape, gene expression profile, immunological characteristics, tumor microenvironment features) and imaging data (PET scan results, baseline TMTV and TLG values) |
| To assess the prognostic role of interim PET scan in term of Overall Survival | From the beginning to the end of the study (up to 24 months) | OS stratified according to interim PET result |
| To assess the prognostic role of end of treatment PET scan in term of Overall Survival | From the beginning to the end of the study (up to 24 months) | OS stratified according to EOT PET result |
| To assess the prognostic role of end of treatment PET scan in term of Progression Free Survival | From the beginning to the end of the study (up to 24 months) | PFS stratified according to EOT PET result |
| To assess the prognostic role of baseline Total Metabolic Tumor Volume in term of Overall Survival | From the beginning to the end of the study (up to 24 months) | OS stratified according to baseline PET TMTV |
| To assess the prognostic role of baseline Total Metabolic Tumor Volume in term of Progression Free Survival | From the beginning to the end of the study (up to 24 months) | PFS stratified according to baseline PET TMTV |
| To assess the prognostic role of baseline Total Lesion Glycolysis in term of Overall Survival | From the beginning to the end of the study (up to 24 months) | OS stratified according to baseline PET TLG |
| To assess the prognostic role of baseline Total Lesion Glycolysis in term of Progression Free Survival | From the beginning to the end of the study (up to 24 months) | PFS stratified according to baseline PET TLG |
| To assess predictive factors of Progression Free Survival | From the beginning to the end of the study (up to 24 months) | Investigate if one or more PFS predictive factors could be identify among clinical data, biological data (presence of ALK, DUSP22, TP63 alterations, mutational landscape, gene expression profile, immunological characteristics, tumor microenvironment features) and imaging data (PET scan results, baseline TMTV and TLG values) |
| To assess predictive factors of Overall Survival | From the beginning to the end of the study (up to 24 months) | Investigate if one or more OS predictive factors could be identify among clinical data, biological data (presence of ALK, DUSP22, TP63 alterations, mutational landscape, gene expression profile, immunological characteristics, tumor microenvironment features) and imaging data (PET scan results, baseline TMTV and TLG values) |
| To explore the role of ASCT consolidation in term of Progression Free Survival | From the beginning to the end of the study (up to 24 months) | PFS stratified with and without ASCT consolidation |
| To explore the role of ASCT consolidation in term of Overall Survival | From the beginning to the end of the study (up to 24 months) | OS stratified with and without ASCT consolidation |
Countries
Italy
Contacts
CONTACTUffici Studi FIL
PRINCIPAL_INVESTIGATORCarla Minoia, MD
Bari - I.R.C.C.S. Istituto Tumori Giovanni Paolo II - U.O.C. Ematologia
Outcome results
None listed