High response rate but significant toxicity with sequential high-dose ifosfamide (I), carboplatin (C), and etoposide (E) with rituximab for relapsed Hodgkin’s (HD) and large cell non-Hodgkin’s lymphoma (NHL)

Abstract

6700 Background Ifosfamide, Carboplatin and Etoposide (ICE) are commonly used for the treatment of recurrent HD and NHL prior to autologous stem cell transplantation (ASCT). Since maximizing the single agent dose intensity of each component of a combination regimen has led to improved outcomes in breast cancer, we studied such an approach in lymphoma by developing a regimen in which patients received the dosage equivalents of 3 cycles of combination ICE therapy as sequential single agent treatments. Methods 22 patients (21 evaluable) with relapsed or refractory Hodgkin’s (9) or non-Hodgkin’s Lymphoma (12) received 15 g/m2 I with hydration and mesna, followed by 900 mg/m2 E, followed by C at an AUC of 15 every 21 days. NHL pts received 375 mg/m2 of R with each cycle. Pts received E as the second agent and stem cell apheresis following count recovery prior to receiving C. CR, PR, or SD pts then proceeded to ASCT with CBV (9 pts) or BEAM (6 pts). Prophylactic antibiotics and G-CSF were administered with each cycle of therapy. Results Severe toxicity consisted of 7 episodes of hospitalization for F&N, one large pleural effusion, one pt with transient grade 4 neurotoxicity and irreversible grade 4 renal failure and one pt with grade 3 renal failure. Following institution of a mandatory 12-hour interval between R and I, no serious renal toxicity was observed in the next 13 pts. Two treatment deaths occurred; one from sepsis in the pt on dialysis and a 2nd pt who died of neutropenic sepsis following C. One pt died during transplant of diffuse pulmonary thrombosis. Four pts achieved CR, 9 PR, 2 SD, 4 PD pre-ASCT. Three pts were not evaluable for response due to either early death (1), withdrawal due to AE (1), or missing data (1). 11 of 15 transplanted pts achieved CR; 7 (47%) remain in CR at a median f/u of 27 months. Conclusions This regimen has significant activity, but is more toxic than when administered in a conventional manner. The current remission rate post SCT is encouraging in these advanced disease pts but it is unclear if it is greater than that achieved with standard salvage regimens followed by ASCT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen, Bristol-Myers Squibb