Randomized Comparison of G-CSF Versus GM-CSF + High Dose Chemotherapy for Peripheral Blood Stem Cell Mobilization and Autologous Transplantation in Multiple Myeloma
Arora, M.; Burns, L.J.; Barker, J.N.; Miller, J.F.; Olujohungbe, A.B.; Weisdorf, D.J.
Blood 100(11): Abstract No. 405
Multiple myeloma is a malignant proliferation of plasma cells which despite multi-agent combination chemotherapy, is not curable with conventional therapy. Autologous PBSCT appears to offer higher response rates and improved survival rates. However this requires effective cytoreduction and rapid hematologic reconstitution to allow moderation of transplant associated morbidity and mortality. We conducted a randomized clinical trial to assess the efficacy of combination chemotherapy + G-CSF versus GM-CSF for PBSC mobilization and engraftment followed by autologous transplantation. The percentage of patients achieving CR to total therapy determined at day +28, +100 or 6 months post transplant and overall and disease free survival were major end points of the study. Eligible patient received Cyclophospamide (4gm/m2), Mitoxantrone (8gm/m2 QD x 2 days) & Dexamethasone (20mg/m2 Q 12 hours x 2 days) followed by randomization to either GM-CSF or G-CSF daily until completion of third or final leukapharesis. For each of the 2 cycles of chemo priming patients were followed daily with outpatient visits till completion of leukapharesis. Cytoreductive preparation for transplant was with Cyclophosphamide (75mg/kg QD x 2 days) + TBI (165 cGy BID x 3 days). Maintainance immunotherapy with alpha interferon was used post transplant. We report interim results on 54 patients. 68% of patients had stage III disease at diagnosis, 54% underwent more than 4 cycles of initial chemotherapy & 13% had only minimal response to initial treatment. Median age at transplant was 52 years and the median time from diagnosis to transplant was 10 months. Median CD34+ cells obtained post mobilization was 5.30x106/kg (1.10-51.49x106/kg) in G-CSF arm and 12.50x106/kg (2.78-94.52x106/kg) in the GM-CSF arm (p=0.1). Engraftment (ANC >500/mul) occurred at a median of 10 days (8-13 days) in the G-CSF arm and 9 days (2-52days) in the GM-CSF arm (p=0.06) . Platelet recovery was prompt at 14 days (8-365) in the G-CSF arm versus 18 days (10-86) in the GM-CSF arm (p=0.03). Response, overall and disease free survival were similar in both cohorts. Overall, 39% of the patients achieved CR following priming chemotherapy which improved to 50% post transplant. Additional 35% of patients attained a PR post transplant for a total response rate of 85%. After a median follow-up of 1.64 years (0.03-6.6 years) 61% of patients relapsed or progressed. The median time to progression was 1 year post transplant (0.06-5.05 years). The overall survival was 86% (76%-96%) at one year, 73% (60%-86%) at 1.6 years, and 56% (40%-73%) at 3 years post transplant. Relapse or progression free survival of 68% ( 54%-81% ) at 1 year, 50% (34%-66%) at 1.6 years and 36% (20%-53%) at 3 years was seen. 2 early transplant related deaths were seen. ( VOD + intracranial bleed; RSV pneumonitis). 3 (5.5%) patients developed significant toxicities associated with priming chemotherapy. (Parainfluenza + renal failure; aspergillus and MI). 4 (7.4%) patients developed secondary MDS at a median of 1.4 years (1-2 years) post transplant. Conclusion: Mobilization with chemotherapy + G-CSF versus GM-CSF results in similar CD34+ progenitor cell counts. Early engraftment was seen with both. High dose therapy with autologous stem cell transplant improved CR rates.