Outcome of Transplant-Eligible Patients with Hodgkin Lymphoma with An Inadequate Response to Second Line Chemotherapy with Gemcitabine, Dexamethasone, Cisplatin (GDP).

Introduction: Standard practice for patients (pts) with Hodgkin Lymphoma (HL) who relapse or are refractory to primary therapy is second line chemotherapy followed by an autologous hematopoietic cell transplant (AHCT) in those who demonstrate chemotherapysensitive disease. Management of pts who achieve less than a partial remission (PR) to first line salvage chemotherapy is unclear. We evaluated the utility of further chemotherapy in pts unresponsive to GDP and to determine transplant outcomes of pts with stable disease (SD).

Methods: This was a retrospective, single centre study of 118 pts from 2001–2008 with refractory/relapsed HL after ABVD or equivalent chemotherapy who were eligible for AHCT and received GDP as first line salvage chemotherapy. Patients undergoing AHCT had progenitor cells mobilized with cyclophosphamide (2g/m² D1), etoposide (200mg/ m² D1–3) and G-CSF. Intensive therapy consisted of etoposide 60mg/kg and melphalan 180mg/m². Involved field radiation was given after AHCT to disease sites > 5cm. Response assessment prior to AHCT was performed using CT +/−gallium scan. Patients achieving PR or complete remission (CR) to GDP proceeded to AHCT. Pts with progressive disease (PD) on GDP were offered second line salvage chemotherapy with miniBEAM (MB; melphalan, etoposide, cytarabine, BCNU). Patients with SD post GDP were generally given further MB if residual mass was >5cm or if they remained gallium avid.

Results: Median age was 38, (range 18–65), 42% were female, 80% had nodular sclerosis HL. At diagnosis, 21% had limited stage (1A/2A); 29% received radiotherapy. At relapse/ progression 36% had limited stage; 25% had B symptoms; 39% had primary refractory disease; median largest mass size was 4cm (range 1–12cm). Median follow up for transplanted (n=110) and non-transplanted (n=8) pts was 25.2 and 19 months, respectively. Response rate (PR+CR) to GDP chemotherapy was 75% (88/118). Response to GDP was unknown in 1 pt. 21 patients had SD and 8 had PD. 8 pts with SD post-GDP received MB resulting in 1 PR, 4 SD (1 gallium avid) and 3 PD. Eight pts with PD post-GDP received MB resulting in 4 PR, 1 SD (gallium avid) and 3 PD. Of the 16 MB pts, 8 responded adequately (PR or SD and gallium negative) and proceeded to AHCT. Median PFS for these 8 transplanted pts was 3.5 months (range 1–23), 2 year PFS was 23%. Of the 16 pts who received MB, only 3 (19%) remain in remission, 2 with less than 6 months follow up. We compared the disease characteristics (age, gender, mass size, stage, B symptoms, time to relapse) at first relapse/progression between the pts in SD transplanted after GDP alone to the 8 pts transplanted after MB. Patients receiving MB and AHCT were more likely to have B symptoms at relapse compared to pts with SD transplanted after GDP alone, p=0.048). For pts undergoing AHCT after GDP alone, 2 year PFS for those achieving PR/CR (n=88) to GDP compared to those only achieving SD (n=13) was similar − 69% for both groups (95%CI 59–81% for PR/CR and 48–99% for SD). No difference in disease characteristics at relapse was noted between the two groups.

Conclusion: Selected patients (i.e. those with low bulk who are gallium negative) transplanted in SD after GDP have a comparable outcome to those transplanted in PR/CR. Patients who require additional therapy to achieve disease control prior to AHCT have a high relapse rate despite aggressive treatment. Additional studies evaluating functional imaging to direct further therapy and novel treatment strategies for pts with an inadequate response to chemotherapy pre-AHCT are warranted.