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Phase I study of selinexor-DICE in relapsed PTCL and NKTL
died. The median overall survival was not reached and the 1-year overall survival rate was 66.7% (95% confidence interval: 28.2-87.8%) (Figure 1).
Discussion
In this study of Asian patients with relapsed or refracto- ry TCL, we found that the maximum tolerated dose of selinexor that could be combined with high-dose dexam- ethasone and standard dose ICE i.e., DICE, in a 21-day cycle, was 40 mg on days 3, 5 and 7. The combination was highly active with a response rate of 100% among the
evaluable patients. However, toxicities were significant. Patients ineligible for HDC/autologous SCT underwent a median of 3.5 cycles of this treatment, and five of 11 (45.5%) discontinued treatment for reasons other than disease progression or a lack of response.
Hyponatremia is a known and well-established adverse event associated with selinexor and was the most com- mon non-hematologic adverse event that occurred in this study. All-grade hyponatremia occurred after selinexor was administered, was transient and resolved after a median of 7 days from the onset. Patients who developed hyponatremia were generally asymptomatic and managed with oral rehydration salts, sodium tablets, intravenous
Table 2. Disposition of the patients.
Figure 1. Kaplan-Meier plot of overall survival in the efficacy population.
Patient
1 2 3 4
5
6 7
8
9
Age Dose Eligibility (in years)/ level for
gender HDC/ASCT
70/Male 1 No 38/Female 1 Yes 52/Male 1 No
61/Male 2 No 52/Male 2 Yes
60/Male 2 No 49/Male 2 No
34/Male 2 Yes 67/Male 1 No
Reasons for HDC/ASCT ineligibility
Advanced age NA
Prior HDC/ASCT Poor heart function EF 36% from IHD NA
NKTL*
Poor heart function EF 45% from non-ischemic cardiomyopathy NA
Advanced age
Advanced age
Advanced age
Number of treatment cycles completed
2 3 4 6
5
6 6
3
3
3
1
Reasons for treatment discontinuation
Maintenance selinexor treatment
10 74/Female 1 No
11 68/Male 1 No
Patient’s decision No Proceeded to HDC/ASCT No Adverse events Yes
Completed 6 cycles Yes
Proceeded to No allogeneic transplant
Completed 6 cycles No Completed 6 cycles No
Proceeded to HDC/ASCT No
Investigator’s decision No
Patient’s decision No
Adverse events No
HDC/ASCT: high-dose chemotherapy and autologous stem cell transplantation; NA: not applicable; EF: ejection fraction; IHD: ischemic heart disease; NKTL: natural-killer/T-cell lymphoma. *HDC/ASCT in not performed for NKTL in our institution due to historical lack of efficacy and this patient declined an allogeneic stem cell transplant.
haematologica | 2021; 106(12)
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