CAG Regimen Shows Strong Results as Salvage Therapy in T-ALL

A new multicenter trial suggests a chemotherapy regimen most commonly associated with acute myeloid leukemia (AML) might be the best salvage therapy for patients with relapsed or refractory T-cell lymphoblastic leukemia (R/R-T-ALL).

Investigators in China say the cytarabine, aclarubicin, and G-SCF (CAG) regimen is highly effective and safe in patients with R/R-T-ALL, confirming the experience of a single cancer center’s smaller study. The new research may help build consensus in a therapeutic area in which patients face stiff odds and no single salvage therapy has emerged as the standard of care.

Writing in the journal Cancer Medicine,¹ a team of investigators including Hong-Hu Zhu, MD, PhD, of the First Affiliated Hospital of Zhejiang University, in China, notes that patients who are newly diagnosed with T-ALL have been treated more successfully in recent years, but survival among patients with relapsed or refractory T-ALL face long-term survival rates of less than 10%.

“The only curable treatment is initiating a salvage regimen to achieve complete remission (CR) and then rapidly performing allogeneic hematopoietic stem cell transplantation (allo-HSCT),” the authors write. “Therefore, selecting an effective salvage regimen is vital for R/R-T-ALL.”

That’s where the trouble comes in, though. Zhu and colleagues note that although a number of regimens are being used, there is no consensus on the optimal therapy. Back in 2008, a team of Chinese investigators published findings² showing promising results with the CAG regimen, but the study size was small.

In an effort to better evaluate the regimen, Zhu and his team constructed a 6-center retrospective analysis of patients with R/R-T-ALL who were at least 16 years old and who underwent the CAG regimen as salvage therapy between 2012 and 2019. The team measured complete remission (CR), partial response (PR), overall survival (OS), and event-free survival (EFS).

Out of a total of 41 patients, 33 achieved CR after one cycle of the CAG regimen, and 2 more patients achieved PR. Six patients failed to respond. Early T-cell precursor status did not affect CR rates, which were around 80% for both ETP and non-ETP patients.

Of the 41 patients, 27 underwent successful allo-HSCT, the majority of whom (22) were in CR. After 2 years, OS was estimated at 68.8% and EFS was estimated at 56.5%.

“Our multicenter results show that the CAG regimen is associated with a high CR rate of 80.5% and is well-tolerated, enabling most patients to bridge to allo-HSCT,” Zhu and colleagues report. “Thus, this regimen represents a novel option for adult R/R-T-ALL patients.”

Zhu and colleagues said the most surprising finding was the “very high” overall response rate of 85.4%. Furthermore, the fact that 66% of patients were able to bridge to allo-HSCT was highly encouraging, they said. The investigators note that the regimen is most commonly used in China for the treatment of acute myeloid leukemia (AML).

The CAG regimen seems to have low rates of hematological and non-hematological adverse events, something found in the current study but also in use in AML.

The authors note that the cancer is so rare that it will be difficult to study in much larger trials, though they are currently planning a study that will include 18 cancer centers in China to validate the results. In the meantime, they write that the regimen represents a ray of hope in a difficult disease category.

“The CAG regimen enabled most patients to bridge to allo-HSCT and achieve improved outcomes; thus, it represents a novel option for this population with poor prognosis,” they conclude.

References:

1. Qian JJ, Hu X, Wang Y, et al. CAG regimen for refractory or relapsed adult T-cell acute lymphoblastic leukemia: A retrospective, multicenter, cohort study. Cancer Med. [Published online June 3, 2020]. doi:10.1002/cam4.3079
2. Xue SL, Wu DP, Sun AN, Tang XW. CAG regimen enables relapsed or refractory T-cell acute lymphocytic leukemia patients to achieve complete remission: a report of six cases. Am J Hematol. 2008;83(2):167‐170. doi:10.1002/ajh.21066