Dr Jakubowiak on the Design of the Phase 3 ATLAS Trial in Multiple Myeloma

“This study is a good example of how we can [perform] investigator-initiated studies with international [collaboration] which is evaluating [a regimen] that will challenge the current standard of care.”

Andrzej Jakubowiak, MD, PhD, a professor of medicine and the director of the Myeloma Program at University of Chicago Medicine, discussed the key design characteristics of the phase 3 ATLAS study (NCT02659293), which evaluated maintenance carfilzomib, lenalidomide (Revlimid), and dexamethasone (KRd) following autologous stem cell transplantation (ASCT) for the treatment of patients with newly diagnosed multiple myeloma.

ATLAS was an international open-label clinical trial that enrolled patients with newly diagnosed disease who received any induction therapy for up to 1 year followed by single ASCT and the achievement of at least stable disease within 100 days, Jakubowiak began. He added that the study was initiated at a time when minimal residual disease and high-risk cytogenetic standards differed from the present day. It enrolled a total of 180 patients, he noted.

Patients were randomly assigned 1:1 to receive KRd or lenalidomide alone. Patients in the KRd arm received carfilzomib at 36 mg/m2 on days 1, 2, 8, 9, 15, and 16 of cycles 1 to 4, then days 1, 2, 15, and 16 in cycles 5 to 8; lenalidomide at 25 mg on days 1 to 21 of cycles 1 to 8; and dexamethasone at 20 mg on days 1, 8, 15, and 22 of cycles 1 to 8. From cycles 9 to 36 patients who achieved MRD negativity and standard-risk disease received lenalidomide monotherapy at 15 mg on days 1 to 28 of cycles 9 to 36. Those with MRD-negative, high-risk disease after cycle 8 continued on the same KRd regimen used in cycles 5 to 8.

In the lenalidomide alone arm, patients received the agent at 10 mg days 1 to 28 of cycles 1 to 3 which was allowed to escalate to 15 mg per day in cycle 4; treatment continued for 36 cycles. Following cycle 36, all patients in both arms received lenalidomide monotherapy.

The primary end point was progression-free survival. Overall survival, MRD status, and safety served as the study’s secondary end points.