Maintenance Carfilzomib Plus Lenalidomide and Dexamethasone Following Autologous HSCT for Newly Diagnosed Multiple Myeloma

Key Clinical Summary: 

• Design/Population: The phase 3 ATLAS trial randomized 180 patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation to receive either carfilzomib plus lenalidomide and dexamethasone or lenalidomide alone. The primary end point was progression-free survival.
• Key Outcomes: Triplet maintenance significantly improved progression-free survival compared with lenalidomide alone, with a substantial increase in long-term disease control. Safety profiles were manageable, with expected hematologic toxicities.
• Clinical Relevance: These findings support maintenance intensification in selected patients following transplant. Risk-adapted strategies incorporating measurable residual disease may help balance efficacy and toxicity.

Results from the phase 3 ATLAS trial demonstrate that carfilzomib plus lenalidomide and dexamethasone significantly improves progression-free survival (PFS) compared with lenalidomide alone among patients with newly diagnosed multiple myeloma following autologous hematopoietic stem-cell transplantation (aHSCT).

“Lenalidomide maintenance has long been a preferred treatment after [aHSCT] in patients with multiple myeloma,” stated Dominik Dytfeld, MD, Poznan University of Medical Sciences, Poznan, Poland, and coauthors. However, “multidrug treatments are emerging as an alternative to lenalidomide alone.”

In this open-label study, 180 patients who achieved at least stable disease after aHSCT were randomized 1:1 to receive either 20 mg/m² of carfilzomib on days 1 and 2 of cycle 1, then 36 mg/m² on days 1, 2, 8, 9, 15, and 16 for cycles 1 through 4 and on days 1, 2, 15, and 16 for subsequent cycles, plus 25 mg of lenalidomide on days 1 through 21, and 20 mg of dexamethasone on days 1, 8, 15, and 22 (n = 92) or 10 mg of lenalidomide monotherapy for the first 3 cycles followed by up to 15 mg (best tolerated dose) thereafter for 28 days (n = 88) in 28-day cycles.

Patients were stratified by response to prior treatment, cytogenetic risk factors, and treatment location. Patients in the triplet arm with standard cytogenetic risk were permitted to transition to lenalidomide maintenance after cycle 8 if no measurable residual disease was detected after cycle 6. The primary end point was PFS. A key secondary end point was safety.

At a median follow-up of 69 months, median PFS was 72.8 months in the carfilzomib plus lenalidomide and dexamethasone arm and 37.3 months in the lenalidomide monotherapy arm (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.30 to 0.70; P = .0002). The 4-year PFS rates were 67.5% and 38%, respectively (P < .0001).

The most frequently reported grade 3/4 adverse events included neutropenia and thrombocytopenia. Serious adverse events were reported in 30% of patients in the carfilzomib plus lenalidomide and dexamethasone arm and 23% of patients in the lenalidomide monotherapy arm. There were 2 deaths reported in the triplet arm (both due to lung infections) and 2 deaths reported in the lenalidomide monotherapy arm (due to COVID-19 and heart failure). All were considered possibly related to study treatment.

“The enhanced efficacy of carfilzomib [plus] lenalidomide [and] dexamethasone treatment following [aHSCT] in patients with newly diagnosed multiple myeloma, assessed within a framework of de-escalation based on MRD status and individual risk, supports strategies for maintenance therapy intensification in this setting,” concluded Dr Dytfeld et al. 

Source: 

Dytfeld D. Wrobel T, Jamroziak K, et al. Carfilzomib, lenalidomide, and dexamethasone compared with lenalidomide treatment after autologous haematopoietic stem-cell transplantation in patients with multiple myeloma (ATLAS): Primary analysis of a randomised, open-label, phase 3 trial. Lancet Haematol. Published online: March 11, 2026. doi: 10.1016/S2352-3026(26)00011-6