https://orcid.org/0000-0002-5935-0385
Key Points
Moga-CHOP significantly improved 1-year PFS in older patients with aggressive ATL.
CCR4 mutations and Moga-associated cAEs were related to better OS.
No standard of care for older patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 2 weeks with mogamulizumab (Moga; Moga-CHOP-14) for older patients with untreated ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56 to 65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. The primary end point was 1-year progression-free survival (PFS). Secondary end points were the complete response (CR) rate, overall response rate (ORR), overall survival (OS), 1-year event-free survival (EFS), and safety. We also investigated the impact of CC chemokine receptor 4 (CCR4) mutation and Moga-associated cutaneous adverse events (cAEs) on PFS and OS. The study protocol was amended to allow the dosing interval to be extended to 21 days at the physician’s discretion. Among 48 evaluable patients, the 1-year PFS was 36.2% (90% confidence interval, 24.9-47.6), with a median follow-up of 1.6 years. The 1-year OS and EFS were 66.0% and 29.9%, respectively. CR and ORR were 64.6% and 91.7%. No unexpected toxicities were observed. Of 47 patients who received ≥2 cycles of CHOP, 20 (42.6%) received CHOP-14, among whom 12 (25.5%) completed 6 cycles. CCR4 mutation and Moga-associated cAEs were associated with better OS. This study showed that Moga-CHOP significantly improved PFS, although the optimal interval for CHOP remains undetermined. Moga-CHOP is now considered a preferable first-line treatment for this patient population. This trial was registered at https://jrct.mhlw.go.jp/en-top as #jRCTs041180130.
Comments
Response to Comment on the Moga-CHOP Trial in Older Patients with Aggressive ATL
The historical control we used in our trial was the CHOP-14 arm of JCOG9801 (Tsukasaki K, et al. J Clin Oncol. 2007), in which the median age of patients was obviously younger than that of the Moga-CHOP cohort (58 vs. 74 years). The percentage of patients with unfavorable chronic type was relatively higher in our trial compared to JCOG9801 (17% vs 10%), however, when risk was assessed according to the simplified ATL-PI (Katsuya H, et al. J Clin Oncol. 2012) for patients with acute and lymphoma types, the distribution of age-adjusted ATL-PI for low-, intermediate-, and high-risk patients in the overall JCOG9801 cohort (n=105) was 42% , 51%, and 7%, respectively (Toyoda K, et al. Br J Haematol. 2019), compared to 18%, 60%, and 23% in the Moga-CHOP-14 trial (n=40). Thus, the Moga-CHOP-14 trial included a higher proportion of high-risk patients.
Moreover, treatment options involving systemic chemotherapy for older patients with ATL remain limited. In our trial, no patients underwent allogeneic stem cell transplantation. At a median follow-up of 1.6 years, 18 of 48 patients (38%) were alive, and 8 of 48 patients (17%) remained progression-free. Although longer follow-up is needed, Moga-CHOP appears to be a promising treatment option for older patients with ATL.
Shigeru Kusumoto (Aichi Cancer Center)
Makoto Yoshimitsu (Kagoshima University)
Choi Ilseung (Kyushu Cancer Center)
Kenji Ishitsuka (Kagoshima University)
The Importance of Semantic Precision in Trial Reporting
Most notably, the Key Points section states that “Moga-CHOP significantly improved 1-year PFS in older patients with aggressive ATL.” The use of this verb tense implies causality, which cannot be inferred from a single-arm phase 2 study. The comparison relies exclusively on a historical control, and differences in patient selection, supportive care, and baseline prognostic factors could largely account for the observed outcomes. A more precise wording would acknowledge that the regimen was "associated with encouraging PFS compared with historical data". The current phrasing risks conveying to less methodologically trained readers that a new standard of care has been established, which is premature.
More broadly, this highlights the importance of semantic precision when reporting clinical trial results. Small choices in wording can influence how we perceive results - suggesting causality where only correlation exists, for example - and this risk is especially pronounced in high-visibility sections such as Key Points.