Dose Dense Dreifach* Melphalan100 for Multiple Myeloma.

Background: Tandem high dose melphalan therapy with autologous peripheral stem cell support has emerged as standard of care for patients without prohibitive comorbidities. Mucositis and gastrointestinal side effects are the most common extrahematologic side effects. Two previously published studies presented a triple transplant with a conditioning regimen melphalan 100mg/m2 (MEL100) with peripheral stem cell support every two to five months schedule. This dose reduced regimen was implemented to limit those extrahematologic dose limiting side effects in the elderly or high risk population. We are presenting a novel approach that investigates the triple melphalan100/m2 approach on a dose dense, every three weeks schedule in a patient population without significant comorbidities for conventional high dose tandem transplantation.

Patients and methods: Thirteen standard or high risk patients with stageIII multiple myeloma were prospectively treated This population contained eight patients with IgG clonality, 3 IgA, 1 nonsecretory and one light chain isotype. The induction regimens of the thirteen patients were heterogenous and included 5 VAD, 3 DCIE, 2 Thal/Dex, 2 CIE and 1 pulse decadron. Patients had stem cells harvested through peripheral blood leukopheresis, and these cells were divided into three equal sets and frozen. The patients were scheduled to receive Melphalan at 100mg/m2 on day -1, 20, and 41 and then the autologous infusions occurred at day 0, 21, and 42.

Results: All patients were able to receive all three cycles of the MEL100 regimen. Seven patients (54%) received the treatements on the every three week schedule; three treatments (23%) during the second cycle and six treatments (46%) of the third cycle had to be delayed a median of 6 and 4 days respectively. Three patients were managed completely in the outpatient setting, and the average total hospital stay for the three transplants was 18 days. Median progression free survival was 761 days (range 73 – 1571) and the overall survival of this cohort has yet to be reached. No patient had worse than grade II mucositis, and no serious adverse events were recorded.

Conclusions: Our regimen of three consecutive autologous peripheral stem cell transplants with a reduced dose of melphalan at 100mg/m2 given every three weeks is very well tolerated. The progression free survival and overall survival are similar and can be compared favorably with the standard tandem myeloma regimens. Although our data is intriguing, further studies with larger numbers need to be performed to confirm these results.