Gemcitabine-Based Treatment Yields Similar Response Rates, Less Toxicity Than DHAP Before Stem Cell Transplant for Relapsed/Refractory Lymphoma
In the NCIC-CTG LY.12 study, a phase III international noninferiority trial reported in the Journal of Clinical Oncology, Crump and colleagues found that gemcitabine, dexamethasone, and cisplatin (GDP) was associated with a noninferior response rate and similar transplantation rate compared with dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive lymphoma prior to autologous stem cell transplantation. GDP was less toxic and was better at preserving quality of life.
Study Details
In the trial, conducted at 26 Canadian centers, 10 American centers, 1 Australian center, and 18 Italian centers in collaboration with the Gruppo Italiano Studio Linfomi, 619 patients were randomly assigned between August 2003 and November 2011 to receive GDP (n = 310) or DHAP (n = 309); patients with B-cell lymphoma also received rituximab (Rituxan).
Patients received two 21-day cycles of treatment. GDP was given as gemcitabine at 1,000 mg/m2 on days 1 and 8, cisplatin at 75 mg/m2 on day 1, and dexamethasone at 40 mg per day on days 1 to 4; DHAP was given as dexamethasone at 40 mg per day on days 1 to 4, cytarabine at 2 g/m2 over 3 hours once every 12 hours for two doses on day 2, and cisplatin at 100 mg/m2 by 24-hour continuous infusion on day 1.
Responding patients proceeded to stem cell collection and autologous stem cell transplantation. The coprimary endpoints were response rate after two treatment cycles and transplantation rate in the intent-to-treat population. The noninferiority margin for the response rate to GDP relative to DHAP was 10%. The trial will also examine the efficacy of post-transplantation rituximab treatment.
Patients had a median age of 55 years (28% aged > 60 years), and 61% were male. Most patients had stage III or IV and high-intermediate or high-risk disease and had either not achieved remission with initial therapy or had recurrence within 1 year of completing treatment. Overall, 71% had diffuse large B cell lymphoma, 15% had lymphoma transformed from indolent B-cell histology, and 8% had T cell or anaplastic large-cell lymphoma. Among 554 patients with B-cell lymphoma, 411 had received prior rituximab.
Efficacy Outcomes
Response rates after the first two cycles of treatment were 45.2% with GDP vs 44.0% with DHAP (95% confidence interval for difference = −9.0% to 6.7%), meeting the criterion for noninferiority of GDP (P = .005). Transplantation rates were 52.1% vs 49.3% (P = .44). At median follow-up of 53 months, there were no differences in 4-year event-free survival (hazard ratio [HR] = 0.99, P = .95) or overall survival (HR = 1.03, P = .78).
Toxicity
Grade 3 or 4 adverse events during the first two cycles of chemotherapy occurred in 47% of patients in the GDP group vs 61% in the DHAP group (P < .001), including fewer episodes of febrile neutropenia (9% vs23%, P < .001). GDP recipients had a reduced transfusion rate (31% vs47%, P <.001), including during the first two cycles (18% vs 32%, P <.001); fewer required hospitalization (47% vs99%, P< .001), consistent with the expectation that GDP could be administered in the outpatient setting, including a lower rate of hospitalization for adverse events or other illness (18% vs30%, P < .001). Six DHAP recipients and two GDP recipients died as a result of treatment-related complications.
Quality of Life
Quality of life assessed by the Functional Assessment of Cancer Therapy (FACT) total score showed that there was less deterioration from baseline in the GDP vs DHAD groups, with significant differences observed at the end of the first treatment cycle and at the midpoint of the second cycle. At the midpoint of cycle 2, 18% vs 11% of patients had an improved clinically meaningful change score and 33% vs 41% had a worse clinically meaningful change score (P = .04).
The investigators concluded: “For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life…. This treatment can be considered the preferred treatment option for these patients.”
The study was supported by grants from the Canadian Cancer Society Research Institute and by Roche Canada and Eli Lilly Canada.
Michael Crump, MD, of Princess Margaret Cancer Centre, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
