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ATLAS: A PHASE 3 RANDOMIZED TRIAL OF CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE VERSUS LENALIDOMIDE ALONE AFTER STEM-CELL TRANSPLANT FOR MULTIPLE MYELOMA
Author(s): ,
Dominik Dytfeld
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Tomasz Wróbel
Affiliations:
Wroclaw Medical University,Wroclaw,Pologne;Wroclaw Medical University,Wroclaw,Polen;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Poland;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Polen;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Польша;Wroclaw Medical University,Wroclaw,Polen
,
Krzysztof Jamroziak
Affiliations:
Medical University of Warsaw,Warsaw,Pologne;Medical University of Warsaw,Warsaw,Polen;Medical University of Warsaw,Warsaw,Polonia;Medical University of Warsaw,Warsaw,Poland;Medical University of Warsaw,Warsaw,Polonia;Medical University of Warsaw,Warsaw,Polen;Medical University of Warsaw,Warsaw,Polonia;Medical University of Warsaw,Warsaw,Польша;Medical University of Warsaw,Warsaw,Polen
,
Tadeusz Kubicki
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Paweł Robak
Affiliations:
Medical University of Lodz,Lodz,Pologne;Medical University of Lodz,Lodz,Polen;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Poland;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Polen;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Польша;Medical University of Lodz,Lodz,Polen
,
Adam Walter-Croneck
Affiliations:
University of Medical Sciences in Lublin,Lublin,Pologne;University of Medical Sciences in Lublin,Lublin,Polen;University of Medical Sciences in Lublin,Lublin,Polonia;University of Medical Sciences in Lublin,Lublin,Poland;University of Medical Sciences in Lublin,Lublin,Polonia;University of Medical Sciences in Lublin,Lublin,Polen;University of Medical Sciences in Lublin,Lublin,Polonia;University of
,
Jarosław Czyż
Affiliations:
Collegium Medicum ,Bydgoszcz,Pologne;Collegium Medicum ,Bydgoszcz,Polen;Collegium Medicum ,Bydgoszcz,Polonia;Collegium Medicum ,Bydgoszcz,Poland;Collegium Medicum ,Bydgoszcz,Polonia;Collegium Medicum ,Bydgoszcz,Polen;Collegium Medicum ,Bydgoszcz,Polonia;Collegium Medicum ,Bydgoszcz,Польша;Collegium Medicum ,Bydgoszcz,Polen
,
Agata Tyczyńska
Affiliations:
Medical University of Gdansk,Gdansk,Pologne;Medical University of Gdansk,Gdansk,Polen;Medical University of Gdansk,Gdansk,Polonia;Medical University of Gdansk,Gdansk,Poland;Medical University of Gdansk,Gdansk,Polonia;Medical University of Gdansk,Gdansk,Polen;Medical University of Gdansk,Gdansk,Polonia;Medical University of Gdansk,Gdansk,Польша;Medical University of Gdansk,Gdansk,Polen
,
Agnieszka Druzd-Sitek
Affiliations:
Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Pologne;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Polen;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Polonia;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Poland;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Polonia;Maria Sklodow
,
Krzysztof Giannopoulos
Affiliations:
Medical University of Lublin,Lublin,Pologne;Medical University of Lublin,Lublin,Polen;Medical University of Lublin,Lublin,Polonia;Medical University of Lublin,Lublin,Poland;Medical University of Lublin,Lublin,Polonia;Medical University of Lublin,Lublin,Polen;Medical University of Lublin,Lublin,Polonia;Medical University of Lublin,Lublin,Польша;Medical University of Lublin,Lublin,Polen
,
Adam Nowicki
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Tomasz Szczepaniak
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Anna Łojko-Dankowska
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Magdalena Matuszak
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Lidia Gil
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Bartosz Puła
Affiliations:
Institute of Hematology and Blood Transfusion,Warsaw,Pologne;Institute of Hematology and Blood Transfusion,Warsaw,Polen;Institute of Hematology and Blood Transfusion,Warsaw,Polonia;Institute of Hematology and Blood Transfusion,Warsaw,Poland;Institute of Hematology and Blood Transfusion,Warsaw,Polonia;Institute of Hematology and Blood Transfusion,Warsaw,Polen;Institute of Hematology and Blood Trans
,
Justyna Rybka
Affiliations:
Wroclaw Medical University,Wroclaw,Pologne;Wroclaw Medical University,Wroclaw,Polen;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Poland;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Polen;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Польша;Wroclaw Medical University,Wroclaw,Polen
,
Maciej Majcherek
Affiliations:
Wroclaw Medical University,Wroclaw,Pologne;Wroclaw Medical University,Wroclaw,Polen;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Poland;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Polen;Wroclaw Medical University,Wroclaw,Polonia;Wroclaw Medical University,Wroclaw,Польша;Wroclaw Medical University,Wroclaw,Polen
,
Lidia Usnarska-Zubkiewicz
Affiliations:
Institute of Hematology and Blood Transfusion,Warsaw,Pologne;Institute of Hematology and Blood Transfusion,Warsaw,Polen;Institute of Hematology and Blood Transfusion,Warsaw,Polonia;Institute of Hematology and Blood Transfusion,Warsaw,Poland;Institute of Hematology and Blood Transfusion,Warsaw,Polonia;Institute of Hematology and Blood Transfusion,Warsaw,Polen;Institute of Hematology and Blood Trans
,
Łukasz Szukalski
Affiliations:
Medical University of Bydgoszcz,Bydgoszcz,Pologne;Medical University of Bydgoszcz,Bydgoszcz,Polen;Medical University of Bydgoszcz,Bydgoszcz,Polonia;Medical University of Bydgoszcz,Bydgoszcz,Poland;Medical University of Bydgoszcz,Bydgoszcz,Polonia;Medical University of Bydgoszcz,Bydgoszcz,Polen;Medical University of Bydgoszcz,Bydgoszcz,Polonia;Medical University of Bydgoszcz,Bydgoszcz,Польша;Medica
,
Agnieszka Końska
Affiliations:
Institute of Hematology and Blood Transfusion,Warsaw,Pologne;Institute of Hematology and Blood Transfusion,Warsaw,Polen;Institute of Hematology and Blood Transfusion,Warsaw,Polonia;Institute of Hematology and Blood Transfusion,Warsaw,Poland;Institute of Hematology and Blood Transfusion,Warsaw,Polonia;Institute of Hematology and Blood Transfusion,Warsaw,Polen;Institute of Hematology and Blood Trans
,
Jan Maciej Zaucha
Affiliations:
Medical University of Gdansk,Gdansk,Pologne;Medical University of Gdansk,Gdansk,Polen;Medical University of Gdansk,Gdansk,Polonia;Medical University of Gdansk,Gdansk,Poland;Medical University of Gdansk,Gdansk,Polonia;Medical University of Gdansk,Gdansk,Polen;Medical University of Gdansk,Gdansk,Polonia;Medical University of Gdansk,Gdansk,Польша;Medical University of Gdansk,Gdansk,Polen
,
Jan Walewski
Affiliations:
Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Pologne;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Polen;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Polonia;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Poland;Maria Sklodowska-Curie National Research Institute of Oncology,Warsaw,Polonia;Maria Sklodow
,
Damian Mikulski
Affiliations:
Medical University of Lodz,Lodz,Pologne;Medical University of Lodz,Lodz,Polen;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Poland;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Polen;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Польша;Medical University of Lodz,Lodz,Polen
,
Olga Czabak
Affiliations:
University of Medical Sciences in Lublin,Lublin,Pologne;University of Medical Sciences in Lublin,Lublin,Polen;University of Medical Sciences in Lublin,Lublin,Polonia;University of Medical Sciences in Lublin,Lublin,Poland;University of Medical Sciences in Lublin,Lublin,Polonia;University of Medical Sciences in Lublin,Lublin,Polen;University of Medical Sciences in Lublin,Lublin,Polonia;University of
,
Tadeusz Robak
Affiliations:
Medical University of Lodz,Lodz,Pologne;Medical University of Lodz,Lodz,Polen;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Poland;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Polen;Medical University of Lodz,Lodz,Polonia;Medical University of Lodz,Lodz,Польша;Medical University of Lodz,Lodz,Polen
,
Urszula Grzybowska
Affiliations:
Poznan University of Medical Sciences,Poznan,Pologne;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Poland;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Sciences,Poznan,Polen;Poznan University of Medical Sciences,Poznan,Polonia;Poznan University of Medical Scien
,
Oscar B Lahoud
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,États-unis;Memorial Sloan Kettering Cancer Center,New York,Vereinigte Staaten;Memorial Sloan Kettering Cancer Center,New York,Stati Uniti;Memorial Sloan Kettering Cancer Center,New York,United States;Memorial Sloan Kettering Cancer Center,New York,Estados Unidos;Memorial Sloan Kettering Cancer Center,New York,Verenigde Staten;Memorial Sloan Kettering
,
Jeffrey A Zonder
Affiliations:
Karmanos Cancer Institute,Detroit,États-unis;Karmanos Cancer Institute,Detroit,Vereinigte Staaten;Karmanos Cancer Institute,Detroit,Stati Uniti;Karmanos Cancer Institute,Detroit,United States;Karmanos Cancer Institute,Detroit,Estados Unidos;Karmanos Cancer Institute,Detroit,Verenigde Staten;Karmanos Cancer Institute,Detroit,Estados Unidos;Karmanos Cancer Institute,Detroit,United States;Karmanos Ca
,
Kent Griffith
Affiliations:
University of Michigan,Ann Arbor,États-unis;University of Michigan,Ann Arbor,Vereinigte Staaten;University of Michigan,Ann Arbor,Stati Uniti;University of Michigan,Ann Arbor,United States;University of Michigan,Ann Arbor,Estados Unidos;University of Michigan,Ann Arbor,Verenigde Staten;University of Michigan,Ann Arbor,Estados Unidos;University of Michigan,Ann Arbor,United States;University of Michi
,
Andrew Stefka
Affiliations:
University of Chicago,Chicago,États-unis;University of Chicago,Chicago,Vereinigte Staaten;University of Chicago,Chicago,Stati Uniti;University of Chicago,Chicago,United States;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,Verenigde Staten;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,United States;University of Chicago,Chicago,USA
,
Ajay Major
Affiliations:
University of Chicago,Chicago,États-unis;University of Chicago,Chicago,Vereinigte Staaten;University of Chicago,Chicago,Stati Uniti;University of Chicago,Chicago,United States;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,Verenigde Staten;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,United States;University of Chicago,Chicago,USA
,
Benjamin A Derman
Affiliations:
University of Chicago,Chicago,États-unis;University of Chicago,Chicago,Vereinigte Staaten;University of Chicago,Chicago,Stati Uniti;University of Chicago,Chicago,United States;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,Verenigde Staten;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,United States;University of Chicago,Chicago,USA
Andrzej J Jakubowiak
Affiliations:
University of Chicago,Chicago,États-unis;University of Chicago,Chicago,Vereinigte Staaten;University of Chicago,Chicago,Stati Uniti;University of Chicago,Chicago,United States;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,Verenigde Staten;University of Chicago,Chicago,Estados Unidos;University of Chicago,Chicago,United States;University of Chicago,Chicago,USA
(Abstract release date: 05/12/22) EHA Library. Dytfeld D. 06/10/22; 357039; S175
Dominik Dytfeld
Dominik Dytfeld
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S175

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background
Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit of post-ASCT KRd therapy.

Aims
We report the results of ATLAS, a multicenter, international, open-label randomized phase 3 study to determine the efficacy and safety of post-ASCT KRD vs standard lenalidomide (R) maintenance (NCT02659293).

Methods

Newly-diagnosed MM patients (pts) who received any induction therapy for up to 12 months (mo) followed by single ASCT and achieved at least stable disease within 100 days afterward were randomized to receive either KRd or R, stratified by post-transplant response (≥VGPR vs 2 on days (D) 1,2,8,9,15,16 for 4 cycles (C) then D1,2,15,16 starting C5; R 25 mg D1-21, and dexamethasone 20 mg D1,8,15,22 in 28-day cycles. KRd pts with SR who reached IMWG-defined MRD-negativity after C6 de-escalated therapy to R alone after C8 (KRd->R); the rest continued KRd through C36 followed by R alone until progression. Pts randomized to R received lenalidomide 10 mg C1-3 and then 15 mg daily. The primary endpoint was progression free survival (PFS) rate: based on historical PFS rates, a sample size of 180 Pts was calculated to provide 85% power with 2-sided alpha 0.05. Secondary endpoints included minimum residual disease (MRD) negativity response rates and treatment-related adverse events.

Results
180 pts were enrolled (R n=87; KRd n=93) through 10/21/20; data cutoff was 12/31/21. Pt characteristics in the KRd and R arms were balanced for median age (58 vs 59 yrs), ≥VGPR (88% vs 92%), and HR (23% vs 21%). After 6 cycles, 47% pts in the KRd arm and 29% in the R arm achieved MRD-negativity (p=0.017). 34 KRd pts eligible for de-escalation converted to R alone after C8 and were analyzed on the KRd arm per intention-to-treat. At median follow-up of 33.8 mo, 23 pts (25%) on the KRd arm and 38 pts (44%) on the R arm progressed; estimated median PFS was 59.0 mo for KRd vs 41.4 mo for R (Hazard Ratio 0.56, logrank p=0.026). At cutoff, 90% of KRd and 87% of R pts were alive; no deaths were treatment-related. All-grade toxicities were generally comparable between arms. The most common grade 3+ AEs and those of special interest were neutropenia (KRd 47%; R 59%), thrombocytopenia (KRd 13%; R 7%), infections (KRd 15%; R 6%), cardiovascular toxicities (KRd 4%, R 5%), and secondary malignancies (KRd 2, R 2).

Conclusion

This is the first randomized phase 3 trial demonstrating superior PFS with extended post-transplant KRd therapy compared to R maintenance. Therefore, MRD/risk-adapted post-ASCT extended KRd treatment may represent a new standard of care.

Keyword(s): Autologous bone marrow transplant, Multiple myeloma, Phase III, Randomized

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S175

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background
Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit of post-ASCT KRd therapy.

Aims
We report the results of ATLAS, a multicenter, international, open-label randomized phase 3 study to determine the efficacy and safety of post-ASCT KRD vs standard lenalidomide (R) maintenance (NCT02659293).

Methods

Newly-diagnosed MM patients (pts) who received any induction therapy for up to 12 months (mo) followed by single ASCT and achieved at least stable disease within 100 days afterward were randomized to receive either KRd or R, stratified by post-transplant response (≥VGPR vs 2 on days (D) 1,2,8,9,15,16 for 4 cycles (C) then D1,2,15,16 starting C5; R 25 mg D1-21, and dexamethasone 20 mg D1,8,15,22 in 28-day cycles. KRd pts with SR who reached IMWG-defined MRD-negativity after C6 de-escalated therapy to R alone after C8 (KRd->R); the rest continued KRd through C36 followed by R alone until progression. Pts randomized to R received lenalidomide 10 mg C1-3 and then 15 mg daily. The primary endpoint was progression free survival (PFS) rate: based on historical PFS rates, a sample size of 180 Pts was calculated to provide 85% power with 2-sided alpha 0.05. Secondary endpoints included minimum residual disease (MRD) negativity response rates and treatment-related adverse events.

Results
180 pts were enrolled (R n=87; KRd n=93) through 10/21/20; data cutoff was 12/31/21. Pt characteristics in the KRd and R arms were balanced for median age (58 vs 59 yrs), ≥VGPR (88% vs 92%), and HR (23% vs 21%). After 6 cycles, 47% pts in the KRd arm and 29% in the R arm achieved MRD-negativity (p=0.017). 34 KRd pts eligible for de-escalation converted to R alone after C8 and were analyzed on the KRd arm per intention-to-treat. At median follow-up of 33.8 mo, 23 pts (25%) on the KRd arm and 38 pts (44%) on the R arm progressed; estimated median PFS was 59.0 mo for KRd vs 41.4 mo for R (Hazard Ratio 0.56, logrank p=0.026). At cutoff, 90% of KRd and 87% of R pts were alive; no deaths were treatment-related. All-grade toxicities were generally comparable between arms. The most common grade 3+ AEs and those of special interest were neutropenia (KRd 47%; R 59%), thrombocytopenia (KRd 13%; R 7%), infections (KRd 15%; R 6%), cardiovascular toxicities (KRd 4%, R 5%), and secondary malignancies (KRd 2, R 2).

Conclusion

This is the first randomized phase 3 trial demonstrating superior PFS with extended post-transplant KRd therapy compared to R maintenance. Therefore, MRD/risk-adapted post-ASCT extended KRd treatment may represent a new standard of care.

Keyword(s): Autologous bone marrow transplant, Multiple myeloma, Phase III, Randomized

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