A phase I study showed brentuximab vedotin combined with a standard chemotherapy regimen of mitoxantrone, etoposide, and cytarabine may be safe and well tolerated in patients with relapsed/refractory acute myeloid leukemia.
Combination treatment of brentuximab vedotin (BV; Adcetris) with a standard chemotherapy regimen of mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed/refractory acute myeloid leukemia (AML) was found to be safe and well tolerated, according to a study published in Cancer.1
In this phase I, dose escalation clinical trial, 22 patients with CD30-expressing relapsed/refractory AML were given 3 dose levels of BV (0.9 mg/kg, 1.2 mg/kg, and 1.8 mg/kg) on day 1 of a 7-day cycle, followed by the MEC chemotherapy on days 3 through 7. Preliminary efficacy measures showed a composite response rate (CRR) of 36%, with a response rate of 42% among those patients who received the highest dose of BV. Median overall survival (OS) was 9.5 months, with a median disease-free survival of 6.8 months observed among responders.
Febrile neutropenia (64%) was the most common adverse event (AE) noted across all grades, with anorexia (59%) and oral mucositis (55%) also commonly reported. AEs higher than grade 3 included thrombocytopenia (45%) and anemia (32%), with no new toxicities attributable to the study treatment combination of BV and MEC.
“Overall, the results of the current phase I study identified a well-tolerated dose of BV given during reinduction therapy with MEC for patients with CD30- expressing (relapsed/refractory) AML, with a toxicity profile that generally was similar to that of MEC alone,” noted the authors.
The study enrolled 22 patients between May 2013 and April 2018, with a median age of 58 years (range, 23-72 years). Fifteen (68%) were male and 20 (91%) were white. Upon enrollment, 4 patients (18%) had primary refractory disease and 18 patients (82%) had relapsed disease, with 21 (95%) having received prior cytotoxic induction chemotherapy combining an anthracycline with cytarabine as initial induction therapy. One patient (5%) had received high-dose cytarabine.
Due to the smaller sample size, the authors were unable to detect a predictive cytogenetic or molecular pattern for response, but they noted that responses were observed in “patients with adverse risk cytogenetics and unfavorable molecular features.” There was no observed response in patients with primary refractory disease however, which the authors believe suggests the difficulty in overcoming chemoresistance.
“The current study highlighted the challenges of treating patients with (relapsed/refractory) AML,” wrote the authors. “Although several intensive and non-intensive chemotherapy re-induction options currently are available, to the best of our knowledge there has not been a clear preferred option.”
The authors called for additional research and larger studies to confirm the results shown in this phase I study, citing the need to more comprehensively assess the efficacy and toxicity of CD30-targeted therapy in patients with AML.
Narayan R, Blonquist TM, Emadi A, et al. A Phase 1 Study of the Antibody-Drug Conjugate Brentuximab Vedotin with Re-Induction Chemotherapy in Patients with CD30-Expressing Relapsed/Refractory Acute Myeloid Leukemia. Cancer. doi:10.1002/cncr.32657.