Gemcitabine, Dexamethasone, Cisplatin +/- Rituximab (GDP +/- R) Is Highly Effective As a Mobilization Regimen in Relapsed or Refractory Lymphoma (COLLYM STUDY)

Introduction

In relapsed or refractory aggressive lymphoma, LY.12 study demonstrated the noninferiority of GDP, in comparison with DHAP, regarding response rate and overall survival with less toxicity. Because GDP ± Rituximab (R) can be easily given in an outpatient setting, this protocol has become the standard of treatment in many centers. However, no data has been published on the method to mobilize stem cells after GDP. The primary objective of the study was to describe the optimal method for a peripheral blood stem cell mobilization following GDP ± R and compare GDP ± R with intermediate-dose cyclophosphamide (ID-CY) as a secondary objective.

Method

We performed a retrospective observational multicenter study in a cohort of patients treated in one of the three centers located in Montreal and Quebec (CHUM, HMR, HEJ). The study was approved by each local IRB. The inclusion criteria were patients ≥ 18 years with a relapsed of refractory lymphoma who received GDP ± R as a salvage regimen before an autologous stem cells transplantation (ASCT) and who were mobilized on either GDP ± R or ID-CY without the use of plerixafor from January 1^st 2014 to April 30^th 2017. The GDP regimen consisted of gemcitabine 1000 mg/m² IV on days 1 and 8, cisplatin 75 mg/m² on day 1 and dexamethasone 40 mg once daily on day 1 to 4. Data were collected through the patient electronic health records in each hospital. The primary outcome was to define the percentage of patients achieving ≥ 2 x 10⁶ CD34+/kg, the median CD34 yield, the number of days of apheresis and the initial day of apheresis following GDP ± R plus granulocyte-colony stimulating factor (G-CSF). For the secondary outcome, the same parameters were compared with ID-CY. Continuous and nominal variables were compared using Student's t-test and chi-square test respectively.

Results

A total of 27 patients with a median age of 54 years received GDP ± R as a salvage therapy for DLBCL (41%), HL (44%) or follicular lymphoma (15%). G-CSF was started at a daily dose of 5 mcg/kg (52%) or 10 mcg/kg (48%) generally at day 9 or 10 and after 2 (67%) or 3 cycles (26%) of GDP ± R. At the first attempt, all patients (100%) achieved the target of ≥ 2 x 10⁶ CD34+/kg with a median of 7.4 x 10⁶ CD34+/kg (2.5-54.1). The median days of apheresis was 2 (1-5) started after a median of 6 days (± 2) following the beginning of G-CSF. In one of the centers (CHUM) a second day of apheresis was automatically planned because the dosage of CD34 in the collected bags was obtained only the next day. Only 1 patient (4%) consulted to the emergency for a slight bleeding at the jugular catheter in a context of thrombocytopenia in the 21 days following the mobilization. A total of 26 patients have proceeded to an ASCT and they had a neutrophils recovery after a median of 11 days (± 4). In the CHUM, 8 and 12 patients were collected following ID-CY and GDP ± R respectively. They were no difference between ID-CY and GDP ± R regarding the target ≥ 2 x 10⁶ CD34+/kg (100 vs 100%, p=NS) but the mean number of CD34+ collected were significantly higher with GDP ± R (23.2 vs 9.6, p=0.02) in less time (2 vs 3 days, p=0.63). There is a trend toward less consultation to emergency and hospitalization within 21 days of mobilization in favor of GDP ± R (8.3% vs 25%, p=0.33). In the ID-CY group, 2 patients were hospitalized for a short follow-up after the removal of the jugular catheter in a context of thrombocytopenia and febrile neutropenia respectively.

Conclusion

This study demonstrated the feasibility of performing a peripheral blood stem cell mobilization at day 15 following GDP ± R with G-CSF given at day 9 of the second or third cycle. It highly effective and represents a better option due to its simplicity of administration, low rate of hospitalization and low cost.