Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in Advanced-stage diffuse large B-Cell lymphoma

Abstract

PURPOSE In studies of diffuse large B-cell lymphoma, positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. PATIENTS AND METHODS From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. RESULTS At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.

Fig 1.

Treatment schema: R-CHOP dosing: rituximab at 375 mg/m², cyclophosphamide at 1,000 mg/m², doxorubicin at 50 mg/m², vincristine at 1.4 mg/m² (uncapped), and prednisone at 100 mg/d for 5 days. ICE dosing: ifosfamide at 5,000 mg/m² admixed with mesna at 5,000 mg/m² as a 24-hour infusion starting on day 2, carboplatin dosed to achieve an area under the serum concentration-time curve to equal 5 mg/mL (capped at 800 mg) on day 2, and etoposide at 100 mg/m² on days 1 to 3. PET, positron emission tomography; Bx, biopsy; RICE, rituximab + ICE; HDT, high-dose therapy; ASCT, autologous stem-cell transplantation.

Fig 2.

Outcome estimates based on Kaplan-Meier analysis. (A) Progression-free survival (PFS) and overall survival (OS) analyzed by intent to treat. (B) PFS based on interim positron emission tomography with [¹⁸F]fluorodeoxyglucose (FDG-PET): positive versus negative. (C) PFS based on interim FDG-PET and biopsy result: interim FDG-PET–negative versus FDG-PET–positive biopsy-negative versus FDG-PET–positive biopsy-positive. (D) PFS based on histology: diffuse large B-cell lymphoma (DLBCL) versus primary mediastinal DLBCL (PMBL).

Fig 3.

Outcome based on interim evaluation. R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; PET, positron emission tomography; POD, progression of disease; Bx, biopsy; pts, patients; Pos, positive; Neg, negative; PF, progression-free.