In chemotherapy-sensitive patients with newly diagnosed aggressive adult T-cell leukemia/lymphoma (ATL), upfront allogeneic hematopoietic cell transplantation (alloHCT) can be recommended, but its survival benefit remains unclear. This is according to results from a phase III trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
“Aggressive ATL is a poor prognostic disease with a median survival time of around one year on chemotherapy. AlloHCT provides a durable response with a three-year overall survival (OS) rate of around 40%. However, these results were mostly retrospective,” said first author Takuya Fukushima, MD, PhD, of the University of the Ryukyus in Okinawa, Japan. “To confirm the true efficacy and safety, we conducted the single-arm confirmatory phase III trial using alloHCT for untreated ATL.”
The JCOG0907 trial evaluated upfront alloHCT in patients with newly diagnosed aggressive ATL. Eligible patients included those 65 years and younger with an EPOC (endogenous perturbation analysis of cancer) performance status of 0-3 and no central nervous system involvement, Dr. Fukushima said. The primary endpoint was three-year OS for all enrolled patients. Between September 2010 and June 2020, the study enrolled 110 patients (median age = 55 years; 56% female) with the following ALT subtypes: acute (n=72), lymphoma (n=27), unfavorable chronic (n=10), and other (n=1).
“Two patients with favorable chronic ATL and Hodgkin lymphoma proved ineligible after enrollment, but were included in evaluable cases,” Dr. Fukushima said.
Treatment comprised vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP); doxorubicin, ranimustine, and prednisone (AMP); and vindesine, etoposide, carboplatin, and prednisone (VECP) as induction chemotherapy followed by transplantation upon first remission. Myeloablative alloHCT (in patients ≤ 55 years) regimes comprised busulfan/cyclophosphamide for related donors and total body irradiation/cyclophosphamide for HLA-matched unrelated donors. Reduced intensity alloHCT (in patients 56-65 years) regimens comprised busulfan/fludarabine for related donors and fludarabine/busulfan/total body irradiation for unrelated donors. A total of 92 patients received alloHCT (all transplants), of which 41 received it per the study protocol (study transplants) and 51 as post-study treatment, including during first remission in 35 patients and after progression in 16 patients. Eighteen patients did not undergo alloHCT.
The study met its primary endpoint with a three-year OS of 44%. The median survival time was three years for study transplants and 2.5 years for all transplants.
The median time from diagnosis to transplantation was similar for study and post-study transplantation, at 4.7 months and 4.3 months, Dr. Fukushima said. “A total of 76 patients received upfront transplantation,” he added.
The study met its primary endpoint with a three-year OS of 44% (90% CI 36.0-51.6). The median survival time was three years (95% CI 1.5-5.8) for study transplants and 2.5 years (95% CI 1.4-4.8) for all transplants.
“To eliminate immortal time bias, we conducted multivariable analysis with the time-dependent covariate of the presence or absence of transplantation,” Dr. Fukushima said. The hazard ratio (HR) of OS for study transplantation (n=41) versus no study transplantation (n=69; 51 post-study, 18 no transplants) was 0.92 (95% CI 0.55-1.51). “These data indicated that the survival benefit of the study transplantation was unclear,” he said.
On the other hand, the HR of OS for upfront transplantation (n=76; 41 study transplants, 35 post-study during first remission) compared with no transplantation (n=18) was 0.65 (95% CI 0.33-1.1), suggesting that upfront transplantation could provide a survival benefit and “would be recommended for aggressive ATL,” Dr. Fukushima said.
In the 41 patients who underwent study transplants, treatment-related deaths (TRD) occurred in 16.7% of those who received related transplants and in 20.7% of those who received unrelated transplants. Among the 70 patients who died, the causes of death included disease progression in 34, TRD due to protocol treatment in nine, TRD due to post-protocol therapy in 21, and other diseases in six.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Fukushima T, Tsukasaki K, Machida R, et al. Upfront allo-HSCT after intensive chemotherapy for untreated aggressive ATL: JCOG0907, a single-arm, phase 3 trial. Abstract 7001. Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; June 1, 2024; Chicago, Illinois.