14th International Conference on Malignant Lymphoma (ICML)
LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.
The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).
However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.
“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.
He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.
The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.
Efficacy in FL
Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.
Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.
The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.
The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.
The median time to first response was 11.9 weeks and 15.2 weeks, respectively.
None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.
Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.
Efficacy in DLBCL
Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.
Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.
The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.
The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.
The median time to first response was 8.3 weeks and 8.5 weeks, respectively.
Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.
Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.
Predictors of response
Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.
The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.
Safety
Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.
There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).
The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).
Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing.
*Data in the abstract differ from the presentation.