AURORA: A New Dawn

To the Editor—We appreciate the points raised by Camargo and the opportunity to respond. To our knowledge, AURORA was the first randomized, double-blind study to compare 2 oral antiviral agents with a primary end point of cytomegalovirus (CMV) clearance. Identified as limitations of AURORA were the 8-week treatment period (rather than stopping treatment upon viral clearance [1]), dose interruption/reduction of valganciclovir in patients with grade 3 neutropenia, and the rate of treatment-emergent resistance. The 8-week treatment period, which may have overexposed patients to valganciclovir vs clinical practice, was necessary to maintain the double-blind study design and benefit from the efficacy and safety of 8 weeks of maribavir treatment [2, 3]. The primary end point was viremia clearance at week 8, unlike in clinical practice, where the goal is to prevent infection recurrence and end-organ disease by controlling CMV viremia until durable cell-mediated immunity is recovered. Therefore, AURORA required strategies to avoid toxicities and mitigate overexposure/myelosuppression while enabling comparable treatment doses between arms, including dose adjustments, granulocyte colony-stimulating factor use, and therapy interruption [4]. In addition, an original inclusion criterion for AURORA of a viral load (VL) >910 IU/mL was later amended to allow entry of high-risk patients with a VL >455 IU/mL, in line with clinical practice [4, 5]. These patients represented 18% of the study population [4]. Stringent hematology parameters were also required for study entry, likely resulting in underestimation of valganciclovir discontinuation compared with clinical practice. Last, treatment-emergent resistance to maribavir occurred in 9% of patients in AURORA [4], whereas the 26% rate noted was for the refractory CMV patient population in SOLSTICE [6]. Most maribavir breakthrough infections in AURORA were in those with maribavir resistance and cleared after switching to treatments with different mechanisms of action 4]. Acknowledging these limitations, AURORA provided clinically relevant, actionable data [4]. Comparable viremia clearance was achieved during 8 weeks of treatment (maribavir: 83%; valganciclovir: 86%) [4]. Patients had fewer treatment-emergent adverse events (TEAEs), hospitalizations, and TEAE-related discontinuations with maribavir than with valganciclovir, with no maribavir-related deaths [4]. More recurrent CMV infections occurred after the 8-week treatment period with valganciclovir (23% vs 19%) [4]. CMV recurrence has been reported in up to 50%–70% of patients after preemptive therapy [7], likely because maintenance therapy cannot be provided due to the safety and tolerability profiles of conventional agents [8–10]. The authors pose that maintenance therapy at effective doses is a tool to prevent recurrence and associated negative outcomes [11], and this should be confirmed with prospective trials. AURORA confirmed the anti-CMV activity of maribavir with less neutropenia compared with valganciclovir for CMV infection after hematopoietic stem cell transplant [4]. Maribavir's efficacy and safety profile enables clinicians to use it among patients who are at risk of/are experiencing intolerances (eg, myelosuppression, nephrotoxicity) and those who fail to achieve >90% decline in VL after 2 weeks of conventional treatment [4, 12]. These features provide a real benefit for transplant patients despite AURORA not demonstrating noninferiority (within the prespecified 7% margin) of maribavir on CMV viremia clearance at week 8 over valganciclovir. Well-designed, real-world studies are indeed necessary to optimize outcomes with the expanding anti-CMV armamentarium. Financial support. This work was supported by Takeda Development Center Americas, Inc., Lexington, Massachusetts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.