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FRONTMIND: A PHASE III, RANDOMIZED, DOUBLE-BLIND STUDY OF TAFASITAMAB + LENALIDOMIDE + R-CHOP VS R-CHOP ALONE FOR NEWLY DIAGNOSED HIGH-INTERMEDIATE AND HIGH-RISK DIFFUSE LARGE B-CELL LYMPHOMA
Author(s): ,
Umberto Vitolo
Affiliations:
Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italie;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italien;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italia;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italy;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italia;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italië;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Itália;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Италия;Candiolo Cancer Institute, FPO-IRCCS,Candiolo (Torino),Italien
,
Grzegorz S. Nowakowski
Affiliations:
Division of Hematology,Mayo Clinic,Rochester,États-unis;Division of Hematology,Mayo Clinic,Rochester,Vereinigte Staaten;Division of Hematology,Mayo Clinic,Rochester,Stati Uniti;Division of Hematology,Mayo Clinic,Rochester,United States;Division of Hematology,Mayo Clinic,Rochester,Estados Unidos;Division of Hematology,Mayo Clinic,Rochester,Verenigde Staten;Division of Hematology,Mayo Clinic,Rochester,Estados Unidos;Division of Hematology,Mayo Clinic,Rochester,United States;Division of Hematology,Mayo Clinic,Rochester,USA
,
John M. Burke
Affiliations:
Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,États-unis;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,Vereinigte Staaten;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,Stati Uniti;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,United States;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,Estados Unidos;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,Verenigde Staten;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,Estados Unidos;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,United States;Department of Hematology,US Oncology Research and Rocky Mountain Cancer Centers,Aurora,USA
,
Christopher P. Fox
Affiliations:
Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Royaume-uni;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Vereinigtes Königreich;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Regno Unito;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,United Kingdom;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Reino Unido;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Verenigd Koninkrijk;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Reino Unido;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Соединённое Королевство;Department of Clinical Hematology,Nottingham University Hospitals NHS,Nottingham,Storbritannien
,
Marek Trneny
Affiliations:
1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Tchèque, République;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Tschechische Republik;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Rep. Ceca;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Czech;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,República Checa;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Tsjechische Republiek;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,República Tcheca;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Чехия;1st Department of Medicine, First Medical Faculty,Charles University and General University Hospital,Prague,Tjeckien
,
Annalisa Chiappella
Affiliations:
Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italie;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italien;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italia;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italy;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italia;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italië;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Itália;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Италия;Division of Hematology & Stem Cell Transplant,Fondazione IRCCS, Istituto Nazionale dei Tumori,Milan,Italien
,
Maeve Waldron-Lynch
Affiliations:
MorphoSys US,Boston,États-unis;MorphoSys US,Boston,Vereinigte Staaten;MorphoSys US,Boston,Stati Uniti;MorphoSys US,Boston,United States;MorphoSys US,Boston,Estados Unidos;MorphoSys US,Boston,Verenigde Staten;MorphoSys US,Boston,Estados Unidos;MorphoSys US,Boston,United States;MorphoSys US,Boston,USA
,
Nira Hadar
Affiliations:
MorphoSys US,Boston,États-unis;MorphoSys US,Boston,Vereinigte Staaten;MorphoSys US,Boston,Stati Uniti;MorphoSys US,Boston,United States;MorphoSys US,Boston,Estados Unidos;MorphoSys US,Boston,Verenigde Staten;MorphoSys US,Boston,Estados Unidos;MorphoSys US,Boston,United States;MorphoSys US,Boston,USA
,
Alok Pachori
Affiliations:
MorphoSys US,Boston,États-unis;MorphoSys US,Boston,Vereinigte Staaten;MorphoSys US,Boston,Stati Uniti;MorphoSys US,Boston,United States;MorphoSys US,Boston,Estados Unidos;MorphoSys US,Boston,Verenigde Staten;MorphoSys US,Boston,Estados Unidos;MorphoSys US,Boston,United States;MorphoSys US,Boston,USA
Georg Lenz
Affiliations:
Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Allemagne;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Deutschland;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Germania;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Germany;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Alemania;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Duitsland;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Alemanha;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Германия;Department of Medicine A – Haematology and Oncology,University Hospital Münster,Münster,Tyskland
EHA Library. Vitolo U. 06/10/22; 358964; PB2113
Umberto Vitolo
Umberto Vitolo
Contributions
Abstract
References

Abstract: PB2113

Type: Publication Only

Session title: Aggressive Non-Hodgkin lymphoma - Clinical

Background
Up to 40% of patients relapse or are refractory (R/R) to R-CHOP, the current standard of care for diffuse large B-cell lymphoma (DLBCL), indicating an unmet need, particularly in patients with high-intermediate and high-risk disease (International Prognostic Index [IPI] 3–5). POLARIX (NCT03274492) evaluated a modified regimen substituting polatuzumab vedotin for vincristine (pola-R-CHP), demonstrating modest improvement in progression-free survival (PFS) with no overall survival (OS) benefit between treatment arms. The addition of lenalidomide (LEN) to R-CHOP improved both PFS and OS in the Eastern Cooperative Oncology Group (ECOG)-ACRIN E1412 trial but not in the Phase III ROBUST study, in which a lower dose of LEN was used, despite a positive trend toward 2-year PFS in a subgroup analysis.

The chemo-free immunotherapy tafasitamab + LEN, has received accelerated approval in the United States (2020) and conditional marketing authorization in Europe and Canada (2021) in adult patients with R/R DLBCL ineligible for ASCT based on the pivotal L-MIND trial (NCT02399085). The primary analysis of First-MIND (NCT04134936), a Phase Ib randomized safety study of R‑CHOP + tafasitamab ± LEN in patients with previously untreated and newly diagnosed DLBCL, demonstrated that adding tafasitamab + LEN does not impair dosing and scheduling of R-CHOP, with toxicities similar to those expected with R-CHOP alone (ASH 2021; #3556).

Aims
frontMIND (NCT04824092) will investigate the efficacy and safety of R-CHOP + tafasitamab + LEN vs R-CHOP alone in previously untreated patients with high-intermediate and high-risk DLBCL.

Methods
frontMIND is a Phase III, multicenter, randomized, double-blind, placebo-controlled study (Figure). Approximately 880 patients are planned to be randomized at approximately 350 centers in North and South America, Europe, and Asia-Pacific. Eligible patients aged 18‒80 years with previously untreated local biopsy-proven, CD20‑positive DLBCL with IPI score 3–5 (age-adjusted IPI 2–3 if ≤60 years) and ECOG performance score 0–2 will be enrolled. Patients with transformed lymphoma (except double or triple hit lymphoma) are excluded. Patients will be randomized 1:1 to receive six 21-day (D) cycles of either R-CHOP + tafasitamab (12 mg/kg intravenously, D 1, 8, and 15) + LEN (25 mg orally, D1–10) or R-CHOP plus tafasitamab + LEN placebos. Patients will be followed for up to 5 years after the end of treatment. The primary endpoint is investigator-assessed PFS. Secondary endpoints include investigator-assessed event-free survival, OS, safety, and tafasitamab serum concentration (trough and Cmax levels). Sensitivity and specificity of minimal residual disease for early detection of disease progression is an exploratory endpoint; further minimal residual disease parameters may also be investigated.

Results
Results for this study are not yet available: outcome data as described above will be presented in due course.

Conclusion
There remains a high unmet need to improve treatment options for newly diagnosed patients, especially with high-intermediate and high-risk DLBCL (IPI 3–5). The combination of tafasitamab, LEN and R-CHOP may have synergistic potential. Preliminary data from the First-MIND study suggest that tafasitamab ± LEN + R-CHOP may be tolerable in patients with treatment‑naïve DLBCL. The Phase III frontMIND study will provide further evaluation of clinical benefits and safety in patients with newly diagnosed high-intermediate and high-risk DLBCL.

Keyword(s): DLBCL, FrontMIND, Lenalidomide, Tafasitamab

Abstract: PB2113

Type: Publication Only

Session title: Aggressive Non-Hodgkin lymphoma - Clinical

Background
Up to 40% of patients relapse or are refractory (R/R) to R-CHOP, the current standard of care for diffuse large B-cell lymphoma (DLBCL), indicating an unmet need, particularly in patients with high-intermediate and high-risk disease (International Prognostic Index [IPI] 3–5). POLARIX (NCT03274492) evaluated a modified regimen substituting polatuzumab vedotin for vincristine (pola-R-CHP), demonstrating modest improvement in progression-free survival (PFS) with no overall survival (OS) benefit between treatment arms. The addition of lenalidomide (LEN) to R-CHOP improved both PFS and OS in the Eastern Cooperative Oncology Group (ECOG)-ACRIN E1412 trial but not in the Phase III ROBUST study, in which a lower dose of LEN was used, despite a positive trend toward 2-year PFS in a subgroup analysis.

The chemo-free immunotherapy tafasitamab + LEN, has received accelerated approval in the United States (2020) and conditional marketing authorization in Europe and Canada (2021) in adult patients with R/R DLBCL ineligible for ASCT based on the pivotal L-MIND trial (NCT02399085). The primary analysis of First-MIND (NCT04134936), a Phase Ib randomized safety study of R‑CHOP + tafasitamab ± LEN in patients with previously untreated and newly diagnosed DLBCL, demonstrated that adding tafasitamab + LEN does not impair dosing and scheduling of R-CHOP, with toxicities similar to those expected with R-CHOP alone (ASH 2021; #3556).

Aims
frontMIND (NCT04824092) will investigate the efficacy and safety of R-CHOP + tafasitamab + LEN vs R-CHOP alone in previously untreated patients with high-intermediate and high-risk DLBCL.

Methods
frontMIND is a Phase III, multicenter, randomized, double-blind, placebo-controlled study (Figure). Approximately 880 patients are planned to be randomized at approximately 350 centers in North and South America, Europe, and Asia-Pacific. Eligible patients aged 18‒80 years with previously untreated local biopsy-proven, CD20‑positive DLBCL with IPI score 3–5 (age-adjusted IPI 2–3 if ≤60 years) and ECOG performance score 0–2 will be enrolled. Patients with transformed lymphoma (except double or triple hit lymphoma) are excluded. Patients will be randomized 1:1 to receive six 21-day (D) cycles of either R-CHOP + tafasitamab (12 mg/kg intravenously, D 1, 8, and 15) + LEN (25 mg orally, D1–10) or R-CHOP plus tafasitamab + LEN placebos. Patients will be followed for up to 5 years after the end of treatment. The primary endpoint is investigator-assessed PFS. Secondary endpoints include investigator-assessed event-free survival, OS, safety, and tafasitamab serum concentration (trough and Cmax levels). Sensitivity and specificity of minimal residual disease for early detection of disease progression is an exploratory endpoint; further minimal residual disease parameters may also be investigated.

Results
Results for this study are not yet available: outcome data as described above will be presented in due course.

Conclusion
There remains a high unmet need to improve treatment options for newly diagnosed patients, especially with high-intermediate and high-risk DLBCL (IPI 3–5). The combination of tafasitamab, LEN and R-CHOP may have synergistic potential. Preliminary data from the First-MIND study suggest that tafasitamab ± LEN + R-CHOP may be tolerable in patients with treatment‑naïve DLBCL. The Phase III frontMIND study will provide further evaluation of clinical benefits and safety in patients with newly diagnosed high-intermediate and high-risk DLBCL.

Keyword(s): DLBCL, FrontMIND, Lenalidomide, Tafasitamab

Abstract: PB2113

Type: Publication Only

Session title: Aggressive Non-Hodgkin lymphoma - Clinical

Background
Up to 40% of patients relapse or are refractory (R/R) to R-CHOP, the current standard of care for diffuse large B-cell lymphoma (DLBCL), indicating an unmet need, particularly in patients with high-intermediate and high-risk disease (International Prognostic Index [IPI] 3–5). POLARIX (NCT03274492) evaluated a modified regimen substituting polatuzumab vedotin for vincristine (pola-R-CHP), demonstrating modest improvement in progression-free survival (PFS) with no overall survival (OS) benefit between treatment arms. The addition of lenalidomide (LEN) to R-CHOP improved both PFS and OS in the Eastern Cooperative Oncology Group (ECOG)-ACRIN E1412 trial but not in the Phase III ROBUST study, in which a lower dose of LEN was used, despite a positive trend toward 2-year PFS in a subgroup analysis.

The chemo-free immunotherapy tafasitamab + LEN, has received accelerated approval in the United States (2020) and conditional marketing authorization in Europe and Canada (2021) in adult patients with R/R DLBCL ineligible for ASCT based on the pivotal L-MIND trial (NCT02399085). The primary analysis of First-MIND (NCT04134936), a Phase Ib randomized safety study of R‑CHOP + tafasitamab ± LEN in patients with previously untreated and newly diagnosed DLBCL, demonstrated that adding tafasitamab + LEN does not impair dosing and scheduling of R-CHOP, with toxicities similar to those expected with R-CHOP alone (ASH 2021; #3556).

Aims
frontMIND (NCT04824092) will investigate the efficacy and safety of R-CHOP + tafasitamab + LEN vs R-CHOP alone in previously untreated patients with high-intermediate and high-risk DLBCL.

Methods
frontMIND is a Phase III, multicenter, randomized, double-blind, placebo-controlled study (Figure). Approximately 880 patients are planned to be randomized at approximately 350 centers in North and South America, Europe, and Asia-Pacific. Eligible patients aged 18‒80 years with previously untreated local biopsy-proven, CD20‑positive DLBCL with IPI score 3–5 (age-adjusted IPI 2–3 if ≤60 years) and ECOG performance score 0–2 will be enrolled. Patients with transformed lymphoma (except double or triple hit lymphoma) are excluded. Patients will be randomized 1:1 to receive six 21-day (D) cycles of either R-CHOP + tafasitamab (12 mg/kg intravenously, D 1, 8, and 15) + LEN (25 mg orally, D1–10) or R-CHOP plus tafasitamab + LEN placebos. Patients will be followed for up to 5 years after the end of treatment. The primary endpoint is investigator-assessed PFS. Secondary endpoints include investigator-assessed event-free survival, OS, safety, and tafasitamab serum concentration (trough and Cmax levels). Sensitivity and specificity of minimal residual disease for early detection of disease progression is an exploratory endpoint; further minimal residual disease parameters may also be investigated.

Results
Results for this study are not yet available: outcome data as described above will be presented in due course.

Conclusion
There remains a high unmet need to improve treatment options for newly diagnosed patients, especially with high-intermediate and high-risk DLBCL (IPI 3–5). The combination of tafasitamab, LEN and R-CHOP may have synergistic potential. Preliminary data from the First-MIND study suggest that tafasitamab ± LEN + R-CHOP may be tolerable in patients with treatment‑naïve DLBCL. The Phase III frontMIND study will provide further evaluation of clinical benefits and safety in patients with newly diagnosed high-intermediate and high-risk DLBCL.

Keyword(s): DLBCL, FrontMIND, Lenalidomide, Tafasitamab

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