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T. Tang et al.
Patients received a median number of three cycles (range, 1-6) of selinexor-DICE. Three patients were eligible for HDC/SCT. (Table 2) Two patients underwent SCT, one autologous and the other allogeneic SCT. The patient who underwent autologous SCT had 8.52x106/L CD34 cells col- lected prior to the transplant: engraftment of neutrophils and platelets occurred on days 9 and 8, respectively. Engraftment of neutrophils and platelets in the patient who underwent allogeneic SCT occurred on days 10 and 14, respectively. The third patient eligible for HDC experi- enced disease progression just before autologous SCT and he was given alectinib before proceeding to allogeneic SCT. Eight patients were not eligible for HDC/autologous SCT and these patients received a median of 3.5 of the planned six cycles of study treatment (Table 2). Three patients completed all six cycles of study treatment, two patients discontinued treatment because of adverse events, another two refused to continue treatment, and one patient’s treatment was discontinued as a result of the investigator’s decision. Two patients received maintenance selinexor upon completing six cycles of selinexor-ICE.
The most common grade 1 and 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%). Grade 3 or 4 toxicities occurring in at least one patient included thrombocytopenia (82%), anemia (82%), neutropenia (73%), hyponatremia (73%), leukopenia (64%), febrile neutropenia (45%), and one patient each who developed fatigue, anorexia, fever, hypokalemia, sepsis, and an upper respiratory tract infection (Table 3). There were no treat- ment-related deaths. All patients had hyponatremia (any grade), which took a median of 7 days (range, 1 to 21) to resolve. Considering all the cycles of treatment, dose reductions for selinexor, ifosfamide, carboplatin and etoposide were required in five (45%), ten (91%), eight (73%), and nine (82%) of patients, respectively. At DL1 and DL2, the median dose intensities (range) for selinexor were 94.2% (range, 66.7-100%) and 77.8% (range, 72.2- 88.9%), respectively. The median dose intensities for ifos- famide, carboplatin and etoposide were 79.8% (range, 74.8-99.4%), 87.7% (range, 76.9-105.7%), and 73.0% (range, 26.0-98.7%), respectively.
Six and five patients received selinexor at the dose of 40 mg and 60 mg, respectively. Patient 11 developed a dose- limiting toxicity at DL1. He developed a platelet nadir of less than 10x109/L and failed to recover his platelet count to at least 75x109/L by day 28. Two patients developed dose- limiting toxicities at DL2 (patients 5 and 8): one had a platelet nadir of less than 10x109/L on day 11 and in another the platelet count failed to recover to at least 75x109/L by day 28 but did recover by day 32. For these two patients, the platelet counts recovered to 75x109/L within 11 days of the dose-limiting toxicity and they both remained on study. All three patients who developed dose-limiting toxicities had a baseline platelet count of more than 100x109/L. Thus, 40 mg of selinexor was the maximum tolerated dose that could be combined with DICE in this study.
Ten patients were evaluable for response after two cycles of treatment. One patient (patient 11) progressed before he could be evaluated by positron emission tomo- graphy. Of the ten evaluable patients, all responded; nine (82% [95% confidence interval: 48-98]) achieved a com- plete response and one (10%) achieved a partial response (Table 3). The median follow-up of the study was 32.3 months (range, 4.4-36.6). During this period, seven patients experienced disease progression and five patients
Table 1. Baseline demographic data. Characteristic
Age at trial entry, years median (range)
Gender Female Male
Histological subtype AITL
PTCL-NOS
ALCL
NKTL
Other (PTCL with T-follicular helper phenotype)
Ann Arbor staging 2
4
N. of prior chemotherapy regimens
Median (range) 1
2
3
N. (%)
60 (34-74)
2 (18%) 9 (82%)
5 (45%) 2 (18%) 2 (18%) 1 (9%) 1 (9%)
2 (18%) 9 (82%)
2 (1-4) 3 (27%) 5 (45%) 2 (18%)
4 1(9%) Previous treatments
CHOP/CHOPE/CEPP GDP/GEMOX/GIFOX Brentuximab Bendamustine
DHAP Etoposide/cyclophosphamide Pembrolizumab
PUVA
Romidepsin
SMILE
Relapsed or refractory disease Relapsed
Refractory
Prior HDC/ASCT No
Yes
Prior radiotherapy
No
Yes
ECOG performance status
0
1
Eligibility for HDC/ASCT on study entry
No Yes
9 (82%) 6 (55%) 2 (18%) 1 (9%) 1 (9%) 1 (9%) 1 (9%) 1 (9%) 1 (9%) 1 (9%)
4 (36%) 7 (64%)
10 (91%) 1 (9%)
10 (91%) 1 (9%)
3 (27%) 8 (73%)
8 (73%) 3 (27%)
AITL: angioimmunoblastic T-cell lymphoma;, PTCL: peripheral T-cell lymphoma; NOS: not oth- erwise specified; ALCL: anaplastic large cell lymphoma; NKTL: natural-killer/T-cell lymphoma, CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone; CHOPE: cyclophos- phamide, doxorubicin, vincristine, prednisolone, etoposide; CEPP: cyclophosphamide, etopo- side, procarbazine, prednisolone; GDP: gemcitabine, dexamethasone, cisplatin; GEMOX: gem- citabine, oxaliplatin; GIFOX: gemcitabine, ifosfamide, oxaliplatin; DHAP: dexamethasone, high- dose cytarabine, cisplatin; PUVA: psoralen and ultraviolet A; SMILE: steroids, methotrexate, ifos- famide, l-asparaginase, etoposide; HDC/ASCT: high-dose chemotherapy and autologous stem cell transplantation); ECOG: Eastern Cooperative Oncology Group.
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haematologica | 2021; 106(12)