ASH 2015: New therapies explored in peripheral T-cell lymphoma

by Thomas R. Collins: In early results, patients newly diagnosed with peripheral T-cell lymphoma (PTCL) treated with the HDAC-inhibitor belinostat, and CHOP therapy, tolerated the combination well at standard doses, researchers found in a phase 1 dose-escalation study.¹

And among the 21 patients with data that could be evaluated, there was a complete response rate of 67% and an overall response rate of 86%, according to findings presented here at the 57^th Annual Meeting of the American Society of Haematology.

“We felt this was encouraging clinical activity,” said presenter Dr Patrick Johnston, MD, PhD, Assistant Professor of Medicine in the hematology division at Mayo Clinic.

Adverse events were similar to those seen with CHOP therapy — cyclophosphamide, vincristine, doxorubicin and prednisone — alone. A total of 18 of 23 patients had a Grade 3 or 4 adverse event, most commonly neutropenia and anemia.1

Eighteen of the 23 patients, or 78%, were able to complete all planned cycles of the treatment. ¹

“We felt that belinostat and CHOP combination was very well tolerated,” Dr. Johnston said, calling it “a promising new combination regimen in PTCL.” It will be tested more in a Phase 3 randomized trial.

In what investigators say is the first randomized trial in the setting of relapsed or refractory peripheral T-cell lymphoma, patients on the aurora A kinase inhibitor alisertib had an overall response rate that was lower than, but similar to, the rate seen with the use of three alternatives. ²

Patients in the Lumiere trial, conducted over 27 countries, were randomized either to alisertib or to an arm in which investigators chose one of three other therapies: the anti-folate pralatrexate, the HDAC-inhibitor romidepsin, or gemcitabine chemotherapy, which is not yet approved for hematologic cancers. Pralatrexate was chosen in close to half of the cases in the choice arm. ²

Investigators found that 34 of 96 patients, 35%, in the alisertib arm achieved either a partial or a complete response, with a CR of 19%. In the other arm, 39 of 85 patents, 46% had a partial or complete response, with a CR of 28%. The difference wasn’t statistically significant (p=0.077). Forty-four percent of those getting pralatrexate had a complete or partial response; 36% for gemcitabine; and 61% for romidepsin. ²

Progression-free survival time for the two groups also wasn’t statistically different (p=0.177), with a median progression-free survival of 115 days in the alisertib group and 104 days in the investigator-choice group. ²

Rates of serious adverse events and adverse events leading to drug-stoppage were close to identical between the two groups, although anemia and neutropenia were more common in the alisertib group. ²

“Single-agent alisertib demonstrated some activity,” said Owen O’Connor, MD, PhD, Director of the Center for Lymphoid Malignancies at Columbia University. He characterized that activity as “probably comparable” to those agents in the comparator arm.

Investigators are now trying to dig deeper to find patients for whom alisertib might work best.

“There are ongoing exploratory biomarker analyses to try to find out, if possible, which of the patients on the alisertib arm might have markers more likely to be associated with response.”

 

References

 

1.  Johnston P, Cashen A, Nikolinakos P, et al.  Safe and Effective Treatment of Patients with Peripheral T-Cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial. Presented at the 57^th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 253.

2.  O’Connor O, Ozcan M, Jacobsen, et al. First Multicenter, Randomized Phase 3 Study in Patients (Pts) with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL): Alisertib (MLN8237) Versus Investigator’s Choice (Lumiere trial; NCT01482962). Presented at the 57^th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 341.