DA-EPOCH shows promise in newly diagnosed acute lymphoblastic leukemia

Ryan D. Cassaday

SAN DIEGO — Researchers at the ASH Annual Meeting and Exposition reported that dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride yielded “deep remissions” in adults newly diagnosed with acute lymphoblastic leukemia.

Ryan D. Cassaday, MD, attending physician in the Hematologic Malignancies Program at Seattle Cancer Care Alliance and assistant professor in the Division of Hematology at the University of Washington School of Medicine, said these interim results of an ongoing phase 2 trial indicate that dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride (DA-EPOCH) could be used to simplify initial ALL treatment.

“It is simplified even further from the commonly used hyperCVAD regimen, which itself is relatively easy to use by ALL standards,” he said. “That is one way that it potentially makes it appealing, particularly for practitioners who may not be as comfortable treating ALL and don’t have as much experience with some of the more complicated regimens available.”

Cassaday also said DA-EPOCH may serve as a useful backbone regimen in combination with newer ALL treatments.

“There is a lot of interest in trying to combine newer agents with established chemotherapy regimens, but many of those regimens have a lot of toxicity and are complex in and of themselves,” he said. “So, even though EPOCH has efficacy on its own, it may prove to be an easier regimen to which new drugs can be added, whereas other regimens may be too complicated or toxic.”

For the trial, Cassaday and colleagues evaluated 18 adult patients newly diagnosed with ALL who received at least one cycle of DA-EPOCH. The primary endpoint was the rate of complete response as assessed by multiparameter flow cytometry (MFC) after four cycles of treatment or less. The researchers established a stopping rule to cease trial enrollment if fewer than eight patients were MFC negative.

According to the results, 83% of patients achieved morphologic complete remission after one or two cycles of treatment. Fourteen patients were evaluable for the primary endpoint. Among them, eight (57%; 95% CI, 0.29-0.82) were MFC negative after four cycles or less.

The researchers noted that deep remissions were particularly evident among patients with Philadelphia chromosome-positive disease (n = 7) who also received a tyrosine kinase inhibitor (imatinib or dasatinib [Sprycel; Bristol-Myers Squibb, Otsuka]). In this population, the MFC negativity rate was 78%.

The toxicity of DA-EPOCH was manageable, rarely leading to treatment discontinuation or delay, according to the researchers. Eighty-nine percent of patients developed grade three or higher nonhematologic toxicities. The most common toxicities were febrile neutropenia (n = 7), hypofibrinogenemia (n = 4) and gastrointestinal bleeds ( n = 3). One patient died in morphologic CR after three cycles of treatment.

Five patients underwent a hematopoietic cell transplant (HCT), three of whom (all Philadelphia chromosome-positive) were in first CR after receiving DA-EPOCH.

Five patients (33%), including one who underwent HCT, relapsed. At 6 months, the rate of EFS was 61% (median EFS, 8 months) and the OS rate was 94% (median OS not yet reached).

“We passed our initial stopping rule, suggesting that the results are good enough to continue, so enrollment is ongoing,” Cassaday said. “But so far what we have seen based on responses by measurable residual disease, the results are comparable and maybe a little bit better, but not statistically so, than our historical experience with hyperCVAD. Our hope is that if we continue enrolling and continue to achieve good responses, a more precise estimate of the response rate would actually suggest that DA-EPOCH may actually be better than hyperCVAD. However, it is still way too early to make that call.” – by Stephanie Viguers

Reference:

Cassaday RD, et al. Abstract 1419. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosure: Cassaday reports receiving research funding from Amgen, Incyte, Kite Pharma, Pfizer, Merck and Seattle Genetics, and being a consultant for Adaptive Biotechnologies, Amgen, Jazz Pharmaceuticals and Pfizer.