Phase II study of dose-adjusted EPOCH as initial therapy for adults with high-risk acute lymphoblastic leukemia

Abstract

Treatments for adults with newly-diagnosed acute lymphoblastic leukemia (ALL) may be prohibitively toxic and/or resource-intense. To address this, we performed a phase II study of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH). Imatinib or dasatinib was added for Ph + disease; rituximab was added when CD20+. Fifty-three patients were evaluable: 28 with Ph + disease, and 25 with Ph−. All patients had ≥1 high-risk clinical feature. Measurable residual disease-negativity by multiparameter flow cytometry within 4 cycles was achieved in 71% in patients with Ph + ALL and 64% in Ph − ALL. Median overall survival (OS) was 49 months, with a 2-year OS of 71%. Median relapse-free survival (RFS) in the 47 patients that attained morphologic remission was 24 months, with a 2-year RFS of 57%. Early mortality was 2%. In summary, DA-EPOCH yields deep and durable remissions in adults with ALL comparable to some resource-intense strategies but with a low rate of treatment-related death.

Keywords:

• Acute lymphoblastic leukemia
• adult
• chemotherapy
• measurable residual disease
• clinical trial

Disclosure statement

RDC has received research funding from Amgen, Kite/Gilead, Merck, Pfizer, Servier, and Vanda Pharmaceuticals; honoraria/consulting from Amgen, Jazz, Kite/Gilead, and Pfizer; DSMB for Pepromene Bio; independent response review committee for Autolus; and his spouse has been employed by and owned stock in Seagen. MMP has received research funding from Abbvie, Biosight, BMS, Cardiff Oncology, Glycomimetics, Oscotec, Pfizer, and Trillium. PSB has received research funding from Glycomimetics Inc. and Pfizer and is on the medical advisory board for Accordant Health Services (Caremark). JJO has received research funding from Actinium Pharmaceuticals. ARS is employed by and owns stock in Seagen.

Additional information

Funding

This research was supported by a Pilot Award from the Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Cancer Center and National Cancer Institute Support Grant (NCI 5 P30 CA015704-46).