Outpatient Fractionated ICE Protocol in Relapsed/Refractory Lymphomas: Efficacy and Safety

Objectives: The diagnosis of cancer significantly affects quality of life (QoL) of patients. Admission on wards and spending several days far from home to receive chemotherapy, especially in young patients with Hodgkin lymphoma (HL), might negatively affect the QoL. Therefore, we are offering our patients with relapsed and refractory lymphomas receiving the so-called outpatient fractionated regimen of ifosfamide, carboplatin and etoposide (ICE) as salvage treatment prior to high dose chemotherapy and autologous stem cell transplantation (ASCT).

Methods: We retrospectively collected the data of patients who received outpatient fractionated ICE between 2011-2017 at a tertiary care center. The ICE protocol consisted of: ifosfamide 1500 mg/m² infused over 2 h daily on days 1-3, carboplatin (mg dose = 5 · AUC) i.v. on day 1, and etoposide 100 mg/m² i.v. daily on days 1-3, plus filgrastim 5 ug/kg/day s.c. for 5 days. Rituximab 375 mg/m² on day 1 was added for patients with CD20 positive B cell Non-Hodgkin lymphoma. The Cycles of outpatient ICE were given every 21 days.

Results: 89 patients (44% female and 56% male) with median age of 34 years (17-72) fulfilled the inclusion criteria. Majority of patients had HL (64%). 88% had stage III and IV with 60% having B symptoms and 38% extranodal disease prior to ICE. 5% had transformed lymphoma. Mean of received ICE was 2.5 cycles. The complete remission and partial remission rates for primary refractory (63%) and non-primary refractory (37%) disease were 7% and 25% versus 19% and 38% respectively. Of patients who achieved a response qualifying for ASCT, stem cells were successfully collected with filgrastim alone and plerixafor plus filgrastim in 77.1% and 22.9% respectively. The median of collected stem cells was 6.13 10⁶/kg with mean apheresis of two days. 75% of eligible patients proceeded to ASCT. The relapse free survival rate was 45 months (95% CI 10-80) and overall survival rate 58 months (95% CI 32-84). Mean follow-up time was 33.1 months (range 8-92).

The rate of hematological toxicities grade 3 were documented in 15% with 10% neutropenia and 9% thrombocytopenia. Febrile neutropenia rate was 5.6%. Non-hematological toxicities included oral mucositis 3%, vomiting and diarrhea each 1%. No grade 4 or serious adverse events were observed.

Conclusions: Our institutional experience is, to our knowledge, the largest of it is kind, which showed the outpatient fractionated ICE as an interesting alternative to the classic ICE regimen with favorable safety profile. However, for patients with primary refractory lymphomas more effective regimens are urgently needed.