EHA Library - The official digital education library of European Hematology Association (EHA)

Elderly patients are under-represented in clinical trials, especially in studies evaluating intensive salvage combinations for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).  Yet, the risk of developing non-hodgkin lymphomas increases with age, with approximately 50% of patients are diagnosed above the age of 65 years. This leads to uncertainty regarding the  risks and benefits of these treatments, and can have a substantial impact on treatment decisions.

 

To evaluate a 10-year single-center experience and results of therapy using the ifosfamide, carboplatin and etoposide ± rituximab (ICE±R) as a salvage regimen in elderly patients with DLBCL.  

This a retrospective single-center study evaluating the efficacy and tolerability of ICE±R regimen used for the treatment of elderly patients (>70 years) with relapsed or refractory DLBCL. The ICE±R regimen consisted of etoposide (100mg/m²) on day 1-3, carboplatin (dose=5x [25+creatinine clearance], capped at 800mg) and ifosfamide (5000mg/m², mixed with an equal dose of MESNA administrated by continuous infusion over 24 hours) on day 2 ± rituximab (375 mg/m²) given on day 0, as reported  previously.

Data were collected from medical records. Adverse events (AEs) graded according to the Common Terminology Criteria for Adverse Events version 4.0. Disease response was defined according to the revised response criteria for malignant lymphoma. Clinical endpoints were defined according FDA guidance. The study was approved by the local institutional Helsinki ethics committee.

Between October 2003 and June 2014, a total of 32 patients (21 women and 11 men) with DLBCL older than 70 years, were treated in our institute with the ICE±R regimen. 

Median age of the entire cohort was 75.6 years (range 70.6-87.1). Most of the patients had an Ann Arbor stage IV disease (56%, n=18), an intermediate-high to high sIPI (63%, n=20), a low Carlson comorbidity index (0-1 in 81%, n=26), and an excellent ECOG score (0-1 in all cases). 

In 27 patients (84%) the dosage of the chemotherapy was reduced, with a median dose reduction of 25% (range 0-50%). ICE±R was administered in all, except one case, as an in-patient therapy and all received G-CSF as primary prophylaxis. 

The overall response rate observed was 53.1% with a complete response of 40.6%. After median follow-up of 12 months, the median progression free survival (PFS) and overall survival (OS) were 3.9 months and 17.0 months, respectively. Patients who responded to ICE±R (including cases followed by autologous stem-cell transplantation) achieved median PFS of 47.2 months and OS of 78.9 months. Previous response to first-line therapy appeared to be the strongest predictor of response, PFS and OS to second-line treatment. 

Following treatment with ICE±R, an attempt to harvest peripheral blood stem cells was performed in 8 patients. Harvesting was successful in seven patients (>2.5x10⁶ of CD34 cells/Kg) of which six (19%) proceeded to autologous stem-cell transplantation (ASCT). Patients ineligible for ASCT that responded to ICE±R (n=11) were treated with extended cycles of ICE±R (median of 4 cycles per patient), and achieved median PFS of 18.9 months and OS of 21.7 months.

ICE±R was generally well tolerated and major toxicity related mostly to hematological adverse events. 

ICE±R is a safe regimen and achieves high response rates in elderly patients with relapsed or refractory DLBCL. Response to first-line therapy is the strongest predictor of response to ICE±R. Patients with chemosensitive disease, who are not transplant-eligible, should be considered for extended treatment with this regimen.