Dr Jakubowiak on the ATLAS Trial of Carfilzomib, Lenalidomide, and Dexamethasone in Myeloma

“We can do better than single-agent lenalidomide maintenance in the post-transplant [setting]. The time of lenalidomide [monotherapy] is ending and we need objective evidence that there is something better. [Findings from] our earlier study of KRd post-transplant gave us significant evidence that KRd [in this setting] deepens MRD [negativity].”

Andrzej Jakubowiak, MD, PhD, a professor of medicine and the director of the Myeloma Program at University of Chicago Medicine, discussed the rationale for the phase 3 ATLAS study (NCT02659293) in patients with multiple myeloma who have already received autologous stem cell transplantation (ASCT).

ATLAS was an international open-label clinical trial that enrolled patients with newly diagnosed disease who received any induction therapy for up to 1year followed by single ASCT and the achievement of at least stable disease within 100 days. The study randomly assigned patients 1:1 to receive maintenance carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) or lenalidomide maintenance alone. The primary end point was progression-free survival.

Jakubowiak began by noting that he believes the time of single-agent lenalidomide is coming to a close in multiple myeloma, and that better therapies need to continue to be developed. However, objective evidence is needed to confirm this, he qualified.

Additionally, findings from earlier phase clinical trials demonstrated that treatment with KRd following ASCT deepened minimal residual disease (MRD) negativity levels, he noted. More specifically, findings from a phase 2 trial (NCT01816971) showed that patients with newly diagnosed multiple myeloma who received KRd induction and consolidation therapy with ASCT who were evaluable for MRD after 8 cycles of treatment (n = 44) experienced an MRD negativity rate of 60%, which rose to 70% after 8 cycles (n = 43). The best response rate among evaluable patients was 81%. The regimen was also well tolerated, Jakubowiak added.

These findings gave investigators the statistical benchmarks for ATLAS and guided them in determining how the study should be powered, Jakubowiak concluded.