Photo by Larry Young
Huiqiang Huang, MD, PhD
LA JOLLA, CA—Results of a phase 2 study suggest chidamide can produce durable responses in patients with relapsed/refractory natural killer/T-cell lymphoma (NKTCL).
The overall response rate was 57.2% in these patients, and the complete response (CR) rate was 28.6%.
Seven of 14 evaluable patients were still receiving chidamide and still in response at last follow-up. For one patient, this was 50 weeks from initiating treatment with chidamide.
“The response is quite promising and encouraging,” said study investigator Huiqiang Huang, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China.
“In terms of safety, the toxicity is mild to moderate.”
Dr Huang presented these results at the 10th Annual T-cell Lymphoma Forum.
This investigator-sponsored trial enrolled patients with relapsed/refractory non-Hodgkin lymphoma, but Dr Huang presented results in NKTCL patients only.
There were 15 NKTCL patients, most of whom were male (n=12). Their median age was 41 (range, 17-65). All 15 had an ECOG status of 0 or 1, 9 had stage I/II disease, and 6 had B symptoms.
Nine patients had Epstein-Barr virus (EBV) DNA levels of at least 1000 copy/mL at baseline, and 5 patients had lactate dehydrogenase levels of at least 245 U/L.
The patients had a median of 2 prior systemic therapies (range, 1-3), and 2 patients had undergone a transplant.
Efficacy
Patients received chidamide at 2 doses—10 mg daily or 30 mg twice a week. Dr Huang said both doses were effective against the lymphoma types studied, but the 30 mg twice-weekly dose appeared to be more effective for patients with NKTCL.
Fourteen NKTCL patients were evaluable for efficacy, and the median follow-up was 17.6 weeks (range, 2.6-50).
The overall response rate was 68.2% (6/14), and the CR rate was 28.6% (4/14). The disease control rate was 71.4%, meaning 10 of 14 patients had a CR, partial response (PR), or stable disease (SD).
Dr Huang noted that response was associated with elevated H3 acetylation level.
The median time to response was 5.25 weeks (range, 1.1-6.6).
As for duration of response, the 4 complete responders were still on treatment and in CR at last follow-up, which was 22.7 weeks, 38.1 weeks, 41.3 weeks, and 50 weeks, respectively, from treatment initiation.
Three of the 4 partial responders were still on treatment and in PR at 14.1 weeks, 26.9 weeks, and 32 weeks, respectively. Two patients with SD were still on treatment and in SD at 15.3 weeks and 15.9 weeks, respectively.
Three patients progressed while on treatment and died. A fourth patient died 2.6 weeks after treatment initiation.
Safety
Dr Huang noted that adverse events (AEs) were similar with the 2 dose groups. However, patients who received 30 mg biweekly had a higher incidence of gastrointestinal AEs.
Overall, the most common AEs were hematologic—anemia, thrombocytopenia, etc.—but dose reductions allowed for quick resolution of these AEs, according to Dr Huang.
AEs included:
- Lymphopenia—10 grade 1/2 and 1 grade 3/4
- Anemia—9 grade 1/2 and 3 grade 3/4
- Thrombocytopenia—7 grade 1/2 and grade 3/4
- Leukopenia—7 grade 1/2 and 6 grade 3/4
- Increased alanine aminotransferase—7 grade 1/2
- Neutropenia—6 grade 1/2 and 7 grade 3/4
- Increased aspartate aminotransferase—5 grade 1/2
- Hypoalbuminemia—4 grade 1/2
- Nausea—4 grade 1/2 and 1 grade 3/4
- Vomiting—3 grade 1/2
- Mucositis—2 grade 1/2
- Fatigue—2 grade 1/2
- Epistaxis—2 grade 1/2
- Abdominal distension—1 grade 1/2
- Loss of appetite—1 grade 1/2
- Diarrhea—1 grade 1/2
- Hyperbilirubinemia—1 grade 1/2
- Fever—1 grade 1/2 and grade 3/4
- Pain—1 grade 1/2
- Cough—1 grade 1/2
- Constipation—1 grade 1/2.
Dr Huang said EBV reactivation was not confirmed in this study. An elevated EBV DNA load was only observed in 2 patients with progressive disease.
