Non-melphalan based conditioning regimens for tandem autografts in multiple myeloma patients

Abstract

Autologous stem cell transplantation (ASCT) has become a standard therapy for multiple myeloma (MM) patients. In the current study we evaluated the toxicity and efficacy of tandem autografts for MM patients using non-melphalan based conditioning regimens. Patients with stage II and III MM were enrolled in the study after exhibiting response to induction therapy. The treatment plan was designed to harvest a dose of 10 × 106 peripheral blood CD34+ cells/Kg ideal body weight (IBW) for the planned 2 transplants; however, a 2nd ASCT would be pursued only if CR has not been achieved after the 1st ASCT. The 1st conditioning regimen included Busulfan 0.75 mg/Kg PO q6h for 16 doses on days -8 through -5, Etoposide 10mg/Kg IV on days -4 to -2, and Cyclosphosphamide 60 mg/Kg IV on days -3 and -2. The conditioning regimen for the 2nd ASCT included 96 hour continuous infusion of Cyclophosphamide (6 gr/m2) followed by total body irradiation of 600 cGy in 4 fractions over 2 days followed by reinfusion of stem cell product. Thus far, 21 patients have been enrolled, median age of 56 years with median of 191 days from diagnosis to 1st ASCT. All patients completed stem cell harvest successfully. Total of 11 patients did not proceed to 2nd ASCT: 7 patients refused 2nd ASCT, 3 patients had CR after 1st ASCT, and 1 patient was disqualified due to drug induced psychosis during 1st ASCT. Two patients are currently undergoing 2nd ASCT. Eight patients completed tandem autografts. Median CD34+ cell dose and engraftment were similar for both transplants. Median time between the 2 ASCTs was 107 days (range 91–145). One patient with history of gastric bypass died due to liver failure 7 months after 2nd ASCT. Another patient who completed one ASCT died due to disease progression (PD) at 806 days after diagnosis. Overall 3 patients had CR and 3 had very good PR (VGPR) after 1st ASCT (29%), while 5 achieved CR and 1 VGPR after 2nd ASCT with total of 9/21 (43%) with CR+VGPR. At the time of data analysis, 5 of 11 patients who completed only one ASCT showed PD at a median time of 306 days, while only 3 of 8 patients completing the 2nd ASCT had PD at a median time of 562 days. In conclusion, tandem autologous transplants result in higher proportion of MM patients achieving CR, and non-melphalan based conditioning regimens seem to be effective and safe, however a large number of patients remain unwilling to proceed to the 2nd ASCT, mainly because of economical/social reasons.