TOPLINE:

Among patients with multiple myeloma who underwent autologous hematopoietic stem cell transplantation (HSCT), maintenance therapy with carfilzomib-lenalidomide-dexamethasone nearly doubled progression-free survival compared with lenalidomide therapy alone. Many patients were able to switch to lenalidomide monotherapy after 8 cycles of triplet therapy.

METHODOLOGY:

• For patients with newly diagnosed multiple myeloma, lenalidomide maintenance after autologous HSCT is the standard of care. Although intensification of posttransplant maintenance based on measurable residual disease (MRD) appears to improve outcomes, no phase 3 trial has directly confirmed an alternative to be superior to lenalidomide monotherapy.
• The randomized, open-label, phase 3 ATLAS trial tested whether carfilzomib-lenalidomide-dexamethasone maintenance improved disease control compared with lenalidomide alone. It enrolled 180 patients with newly diagnosed multiple myeloma who had at least stable disease after autologous HSCT and randomly assigned them to receive either the triplet regimen (median age, 57 years; n = 92) or lenalidomide (median age, 59 years; n = 88).
• Patients on the triplet regimen received intravenous carfilzomib 20 mg/m² on days 1-2 of cycle 1 and then 36 mg/m² (on days 1, 2, 8, 9, 15, and 16 in cycles 1-4 and days 1, 2, 15, and 16 in cycles 5-36); lenalidomide 25 mg orally on days 1-21; and dexamethasone 20 mg orally weekly in 28‑day cycles. The control arm received lenalidomide 10 mg/d in cycles 1-3 and up to 15 mg/d thereafter in 28-day cycles. Almost half of patients (40/81) who were on the triplet regimen and reached cycle 8 were able to switch to lenalidomide monotherapy, per the MRD and risk criteria.
• The primary endpoint was progression-free survival. Secondary endpoints included MRD status at protocol-specified time points, and safety and tolerability.

TAKEAWAY:

• Over a median follow-up of 69 months, 4-year progression-free survival was 67.5% in the triplet-regimen arm vs 38% in the monotherapy arm (P < .0001). Median length of progression-free survival was 72.8 months vs 37.3 months (hazard ratio [HR], 0.46; P = .0002).
• A complete response or better occurred more often with the triplet regimen vs lenalidomide (91% vs 77%; P = .013). Rates of MRD‑negative status at cycle 6 were higher with the triplet regimen (49% vs 33%; P = .030), as were the rates of MRD‑negative status at best response (73% vs 48%; P = .0007) and sustained MRD‑negative status for at least 12 months (49% vs 22%; P = .0002).
• There was evidence of an overall survival benefit with the triplet regimen (median not reached vs 82.2 months; HR, 0.49). But the trial was not powered to assess overall survival, and there was a delayed separation in the overall survival curves.
• Adverse events of grade 3-4 were more common with the triplet regimen (75% vs 68%), with neutropenia (48% vs 59%) and thrombocytopenia (13% vs 6%) being most common. Serious adverse events occurred in 30% vs 23% of patients. Four on‑study deaths occurred (two in each group), all considered possibly related to treatment.

IN PRACTICE:

“The ATLAS trial results, consistent with the observations from the phase 2 FORTE trial, provide the first evidence from a randomized, controlled, phase 3 study that an alternative to lenalidomide after autologous HSCT improves progression-free survival and overall survival,” the study authors wrote. However, they added, “the observation of an overall survival benefit should be viewed as supportive rather than definitive evidence.”

SOURCE:

The study, led by Dominik Dytfeld, MD, Poznan University of Medical Sciences in Poznan, Poland, was published online in The Lancet Haematology.

LIMITATIONS:

The primary limitation was the shift in standard induction therapy from triplet regimens containing bortezomib to anti-CD38 antibody-based quadruplet therapy during the trial period. The trial was not powered for subgroup analyses in high-risk cytogenetics or for overall survival. Additionally, protocol nonadherence occurred in a small number of patients who underwent treatment de-escalation despite not meeting predefined criteria, reflecting challenges in implementing MRD-guided treatment decisions. 

DISCLOSURES:

The trial was funded by Amgen and Celgene (Bristol Myers Squibb). Several authors reported receiving grants or honoraria from and having other ties with Amgen, Bristol Myers Squibb, and others. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.