Study findings show that despite yielding encouraging response rates, adding decitabine therapy plus vorinostat to chemotherapy is not feasible for patients with relapsed or refractory B-cell ALL (B-ALL) because of a high incidence of significant toxicities (Clin Cancer Res. 2020 Jan 22. Epub ahead of print).

“Treatment failure from drug resistance is the primary reason for relapse in [ALL]….Improving outcomes by targeting mechanisms of drug resistance is a potential solution,” explained Michael J. Burke, MD, Pediatric Oncology, Medical College of Wisconsin, Milwaukee, and colleagues.

Thus, Dr Burke et al conducted a study of 23 pediatric patients (age, 12 years) with relapsed or refractory B-ALL. These patients were treated with decitabine plus vorinostat along with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase.

The most frequently reported toxicities of grade 3-4 included hypokalemia (65%), anemia (78%), febrile neutropenia (57%), hypophosphatemia (43%), leukopenia (61%), hyperbilirubinemia (39%), thrombocytopenia (87%), neutropenia (91%), and hypocalcemia (39%).

In addition, 3 patients had dose-limiting toxicities, including cholestasis, steatosis, hyperbilirubinemia; seizure, somnolence, delirium; and pneumonitis, hypoxia, hyperbilirubinemia.

Of note, infectious complications were common, with 17 (74%) patients having grade >3 infections, including 8 (35%) with invasive fungal infections.

There were 9 (39%) patients who achieved a complete response and 5 (22%) who had stable disease, whereas 9 (39%) were deemed not evaluable for response, primarily because of treatment-related toxicities.

“Correlative pharmacodynamics demonstrated potent in vivo modulation of epigenetic marks, and modulation of biologic pathways associated with functional anti-leukemic effects,” Dr Burke and co-investigators reported.

“Despite encouraging response rates and pharmacodynamics, the combination of decitabine and vorinostat on this intensive chemotherapy backbone was determined not feasible in B-ALL due to the high incidence of significant infectious toxicities,” they concluded.—Hina Porcelli