Contributions
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
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
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
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