Dr Jakubowiak on How the PERSEUS Study Informed the ATLAS Trial in Multiple Myeloma

“[In PERSEUS], the [study authors] were not able to separate out the contribution of post-transplant daratumumab plus lenalidomide maintenance from the remaining portion of the treatment. If we compare a new intervention with standard-of-care lenalidomide, that can potentially move the needle and give us an indication of where we should be heading.”

Andrzej Jakubowiak, MD, PhD, a professor of medicine and the director of the Myeloma Program at University of Chicago Medicine, discussed how findings from the phase 3 PERSEUS trial (NCT03710603) informed the rationale for the phase 3 ATLAS study (NCT02659293) of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma.

PERSEUS examined the addition of daratumumab (Darzalex) to induction and consolidation bortezomib (Velcade), lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma. At a median follow-up of 47.5 months (range, 0-54.4), findings from the study showed that patients who received daratumumab plus VRd (n = 355) achieved a significant progression-free survival (PFS) benefit compared with those who received VRd alone (n = 354; HR, 0.42; 95% CI, 0.30-0.59; P < .001). The estimated 48-month PFS rates were 84.3% (95% CI, 79.5%-88.1%) and 67.7% (95% CI, 62.2%-72.6%), respectively.

Based on these results, the daratumumab plus lenalidomide has been widely adopted in the maintenance setting and other combinations containing CD38-directed agents are being evaluated, Jakubowiak said. However, these findings have not yet been compared with standard-of-care (SOC) therapy, he noted.

Jakubowiak emphasized that all components of the PERSEUS regimen may be important in achieving these results but the contribution of post-transplant daratumumab plus lenalidomide cannot be properly separated from the remaining portions of the treatment.

Thus, the ATLAS trial was designed to compare the investigational arm with SOC maintenance lenalidomide, Jakubowiak said. Findings from this study will be able to properly evaluate the maintenance KRd approach and give investigators a better understanding of where the treatment paradigm should go, he concluded.