A Pilot Phase II Study of C-MOPP-R, Ibritumomab Tiuxetan, and Autologous Transplant for Untreated and Relapsed Follicular Lymphoma: Response, Toxicity, and Feasibility,

We initiated an aggressive treatment protocol for newly diagnosed and relapsed follicular lymphoma in March 2006. This is an IRB approved prospective study registered at clinicaltrials.gov as NCT01130194, which sequentially utilizes three treatment modalities: immunochemotherapy, radioimmunotherapy, and autologous transplantation, in an effort to cure the disease. We report preliminary results of the first twenty patients.

Patients' whose diagnosis of follicular lymphoma was confirmed by our hematopathologists in accordance with the 2008 World Health Organization criteria signed informed consent, and were enrolled in our study. Patients must have had an indication for treatment, stage II-IV disease, any grade, ECOG performance status of 0–1, and adequate organ function to participate. PET/CT has been the standard response tool for follicular lymphoma at our institution since study initiation, and responses were assessed by Cheson criteria.

Treatment consisted of six cycles of C-MOPP-R every 28 days: cyclophosphamide 650mg/m2 IV day 1 and 8, vincristine 1.4mg/m2 IV day 1 and 8, procarbazine 100mg/m2 PO daily day 1–14, prednisone 40mg/m2 PO daily day 1–14, rituximab 375mg/m2 IV day 1 and 8, and pegylated filgrastim 6mg SC day 9. Prophylaxis consisted of a quinolone, TMP-SMX, acyclovir, and fluconazole. Chemotherapy alterations were made at the discretion of the treating physician. Mobilization and collection of hematopoietic stem cells with growth factor was performed in patients with documented response and no residual bone marrow disease after four to six cycles of C-MOPP-R. After completion of C-MOPP-R and recovery of ANC >1000 cells/mcL and platelets to 100K, patients received ibritumomab tiuxetan at standard dosing. Upon second recovery, patients were admitted for BEAM(C) conditioned autologous transplant.

See Table 1 for baseline characteristics. 45% (n=9) of patients received all 3 modalities, 35% (n=7) received C-MOPP-R + radioimmunotherapy, and 20% (n=4) received C-MOPP-R only. The ORR (CR+PR) was 95% (n=19, CR n=18, PR n=1). All responses occurred during C-MOPP-R therapy. The lone non-responder had progressive disease after two cycles of C-MOPP-R. With a median follow-up of 27 months (range 7–54 months), the median event-free survival and overall survival for all 20 patients has not yet been reached. See Figures 1 and 2 for EFS and OS, respectively.

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See Table 2 for toxicity rates during the treatment. Thirty-five percent of patients required a dose reduction or discontinuation of vincristine for peripheral neuropathy. In addition to our lone non-responder, two patients on protocol have died; one of pulmonary hemorrhage thought to be related to BEAC conditioning, and one due to pulmonary embolism and sepsis. One patient received 2 cycles of C-MOPP-R, refused further therapy, relapsed, and is still alive. The main reason for not completing protocol therapy was insurance denial of ibritumomab tiuxetan or autologous transplantation.

Based on our interim analysis of this prospective, ongoing study we propose this therapeutic protocol is an effective and feasible regimen with the possibility of cure for patients with follicular lymphoma. Response rates with C-MOPP-R are excellent and overall, the treatment protocol is well tolerated. Further updates of this cohort and ongoing prospective enrollment on this protocol will help clarify the ultimate role of aggressive therapy in upfront and relapsed follicular lymphoma.

Fesler:Spectrum Pharmaceuticals: Research Funding. Off Label Use: Ibritumomab tiuxetan was utilized off-label for some patients on this study prior to FDA approval in untreated patients. Procarbazine was utilized off-label for patients in this study in spite of proven efficacy as a single agent in non-Hodgkin lymphoma. Petruska:Spectrum Pharmaceuticals: Research Funding.