Carfilzomib, lenalidomide, and dexamethasone outperforms lenalidomide in MM

Phase-3 ATLAS trial shows the post-transplant maintenance therapy benefit of carfilzomib, lenalidomide, and dexamethasone over lenalidomide.

Carfilzomib, lenalidomide, and dexamethasone outperformance observed in post-transplant treatment

In multiple myeloma (MM), lenalidomide maintenance therapy after autologous stem cell transplant (ASCT) has been established as a standard of care1. However, post-ASCT treatment for MM remains an area of active investigation. Previously, a phase 2 trial (NCT01816971) showed an improvement in the depth of response associated with long progression-free survival (PFS) after extended post-ASCT with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction2. Outcomes of the phase 2 FORTE trial (NCT02203643) further supported a benefit of extended KR maintenance3.

In the multicentre, international, phase 3 ATLAS trial (NCT02659293), post-ASCT KRd maintenance therapy was directly compared with standard lenalidomide maintenance therapy. Dr Dominik Dytfeld (Poznan University of Medical Sciences, Poland) presented the outcomes of this still-ongoing trial4

Superior PFS with extended post-transplant KRd maintenance therapy over lenalidome performance

A total of 180 newly-diagnosed MM patients were enrolled. Patients received any induction therapy for up to 12 months followed by single ASCT and achieved at least stable disease within 100 days afterwards before they were randomised 1:1 to receive either KRd or lenalidomide. KRd-treated patients with standard-risk cytogenetics who achieved minimal residual disease (MRD) negativity after 6 cycles of KRd (n=34) crossed over to lenalidomide after 8 cycles KRd; the rest continued on KRd through 36 cycles, followed by lenalidomide maintenance. The primary endpoint was PFS.

MRD negativity (by IMWG criteria) at 6 cycles was reached by 44% of KRd-treated patients and 27% of lenalidomide-treated patients. After a median follow-up of 33.8 months, the median PFS was 59.0 months in the KRd arm versus 41.1 months in the lenalidomide arm (HR 0.56; P=0.026). The benefit of KRd over lenalidomide was observed in all subgroup analyses. Median PFS in patients with standard-risk cytogenetics (n=139) was not reached in the KRd arm versus 65.4 months in the lenalidomide arm (HR 0.44; P=0.01). Overall survival data are still immature. Both treatment regimens were well tolerated. Neutropenia (13% vs 7%) and infections (15% vs 6%) were more common in the KRd arm than in the lenalidomide arm.

“These results indicate superior PFS with extended post-transplant KRd maintenance therapy compared with lenalidomide therapy,” Dr Dytfeld concluded. “In addition, MRD-directed, risk-adapted KRd maintenance could be an alternative to lenalidomide maintenance and may represent a new standard of care.”

1. McCarthy PL, et al. J Clin Oncol. 2017;35:3279–3289.
2. Jasielec JK, et al. Blood. 2020;136:2513–2523.
3. Gay F, et al. Lancet Oncol. 2021;22:1705–1720.
4. Dytfeld D, et al. ATLAS: A phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma. Abstract S175. EHA2022 Hybrid Congress, 09–12 June.