Continuous Infusion Cyclophosphamide and Low Dose Total Body Irradiation (CICy/ldTBI) As a Conditioning Regimen for Tandem Autologous Transplant in Multiple Myeloma

Continuous Infusion Cyclophosphamide and Low Dose Total Body Irradiation (CICy/ldTBI) as a Conditioning Regimen for Tandem Autologous Transplant in Multiple Myeloma

Michael Byrne, John R Wingard, Helen Leather, Jan S Moreb. University of Florida, Division of Hematology/Oncology

Multiple myeloma (MM) remains a largely incurable disease despite recent advances in biologic therapy.  Autologous stem cell transplant (ASCT) is the cornerstone of management yet morbidity and transplant related mortality (TRM) remain concerns for patients and physicians alike.  Between October 2001 and June 2008, 21 MM patients underwent tandem ASCT as part of a prospective phase II clinical study.  After initial ASCT, disease response was assessed at post-transplant day 100 (D+100). Patients achieving ≥ very good partial remission (VGPR) were offered maintenance therapy.  If patients achieved ≤ partial remission (PR), they were offered a second autologous transplant (ASCT2) with a novel conditioning regimen: Continuous IV cyclophosphamide (CICy) 1500mg/m²/day on day -7 through day -4 followed by and low dose total body irradiation (ldTBI) given twice daily at 150 cGy on day -2 and -1. TBI was replaced by melphalan 140 mg/m² if patients had received prior radiation.  Median duration of neutropenia with CICy/ldTBI was 10 days (range, 8-20).  15 patients (71.4%) developed febrile neutropenia.  After fever, grade 1-2 diarrhea was the most common non-hematologic adverse event (42.9%).  One patient each (4.8%) developed a limited subdural bleed, pulmonary embolus, neutropenic colitis, bacterial pneumonia, possible fungal pneumonia, hemorrhagic cystitis, and septic shock.  19 patients (90.5%) required transfusion support (red blood cells, platelets, or both) in the post-transplant period.  All patients were alive at D+100 with no treatment related mortality.  Three patients received CICY and melphalan. After ASCT2, four patients had entered complete remission (CR) (19.0%), seven achieved VGPR (33.3%), while six (28.6%) had PR.  At 4 years after enrollment of last patient, the median progression free survival and overall survival was 21 (range, 7-101) and 38 (range, 12-128) months, respectively. In conclusion, this novel conditioning regimen is safe and effective alternative to high-dose melphalan, and may be useful in patients who do not benefit from first ASCT using other conditioning regimens.