Alisertib, a novel oral aurora A kinase (AAK) inhibitor, has demonstrated antitumor activity in patients with peripheral T-cell lymphoma, according to results from a phase II trial recently published in the Journal of Clinical Oncology. The drug also showed no adverse safety signals, the authors, led by Paul M. Barr, MD, from the University of Rochester Medical Center in Rochester, New York, reported.
Previous early-phase studies showed that alisertib was active in T-cell lymphoma; the current study further investigated the efficacy of alisertib in patients with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL).
“Patients with peripheral T-cell lymphoma tend to have very poor outcomes,” Dr. Barr told ASH Clinical News. “Additional therapeutic options are desperately needed for these patients.” Because AAK is upregulated in highly proliferative lymphomas, AAK-inhibiting alisertib has been proposed as a potential therapeutic target for this patient population.
Dr. Barr and colleagues conducted a phase II Intergroup trial of 37 patients (median age = 62 years; range = 22-86 years) with PTCL. Patients were eligible for study inclusion if they had histologically confirmed relapsed/refractory PTCL or transformed mycosis fungoides (tMF).
A breakdown of the 37 participants’ histologic subtypes included:
- PTCL not otherwise specified (n=13)
- Angioimmunoblastic T-cell lymphoma (n=9)
- tMF (n=7)
- Adult T-cell lymphoma/leukemia (n=4)
- Anaplastic large-cell lymphoma (n=2)
- Extranodal natural killer/T-cell lymphoma (n=2)
The patients had received a median of three prior therapies (range, 1-18 therapies), and three patients had undergone a prior stem cell transplant.
All patients received alisertib 50 mg twice daily for seven days on 21-day cycles until disease progression or unacceptable toxicity.
Two patients experienced complete responses, while seven patients had partial responses, for an overall response rate (ORR) of 24 percent (95% CI 12-41).
Among the PTCL subtypes, the ORR was 33% (95% CI 16-55), but no response was observed for patients with tMF, Dr. Barr and co-authors noted. Of the 27 patients who had available biopsies, zero and six expressed AAK and aurora B kinase (ABK), respectively, thus ABK was more commonly overexpressed compared with AAK in tumor specimen.
On the safety side, treatment-related grade 3 and 4 adverse events (AEs) that occurred in ≥5 percent of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%).
Treatment was discontinued in six patients (most commonly for disease progression), and nine patients reduced their dose due to AEs.
“One of the main take-home points from this [study] is that alisertib is active in this population, suggesting aurora kinase inhibition is worthy of further study in PTCL,” Dr. Barr said. “While some of the patients had prolonged responses, most ultimately progressed, similar to what has been experienced with most other treatment options.” Recent laboratory investigations have suggested notable synergy between alisertib and the histone deacetylase inhibitor romidepsin, he added, and those results are being explored further.
“Alisertib has antitumor activity in PTCL, including heavily pretreated patients,” Dr. Barr and colleagues concluded. “These promising results are being further investigated in an ongoing, international, randomized, phase III trial comparing alisertib with investigator’s choice in PTCL.”
Barr PM, Li H, Spier C, et al. Phase II Intergroup trial of alisertib in relapsed and refractory peripheral T-cell lymphoma and transformed mycosis fungoides: SWOG 1108. J Clin Oncol. 2015;33:2399-2404.