Combined submyeloablative and myeloablative dose intense melphalan results in satisfactory responses with acceptable toxicity in patients with multiple myeloma

We studied in patients with multiple myeloma (MM) the efficacy, cost-effectiveness, and toxicity of a strategy of submyeloablative doses of Mel and stem cell support in the ambulatory setting, followed by a standard myeloablative dose transplant. Patients with recently diagnosed symptomatic MM received dexamethazone to induce clinical response. Cytokine mobilized peripheral blood progenitor cells (PBPC) were split into 2 aliquots and cryopreserved. Patients then received Mel 100 mg/m(2) (Mel100) and infusion of the first PBPC aliquot in an ambulatory facility. Individuals received standard neutropenia prophylaxis and no growth factor support, but were seen regularly at the clinic until recovery. The cost of this step was calculated in a cohort of 23 patients where information for the expenditure was available. Six months later patients were conditioned in the hospital with Mel 200 mg/m(2) (Mel 200) followed by nfusion of the second aliquot. This study tested the cost, effectiveness, and the toxicity of out-patient-based transplantation, as well as the rate of response (complete remission [CR], very good partial remission [VGPR], partial remission [PR], and stable disease [SD]) and overall survival (OS) of this strategy. Twenty-six female and 16 male patients, with a median age of 53 years (range: 33-68 years) and median Salmon & Durie clinical disease stage III (range: II-III) were studied. The paraprotein was IgA in 17%, IgG in 52%, and light chains in 26%. The median harvested CD34(+) x 10(6) cells/kg was 12.03 (2.25-55.4). The median interval between the 2 transplant procedures was 239 (105-376) days. The median Karnofsky presentation score was 40%, but improved to 80% after the Mel 100 and was 90% following Mel 200. Subsequent to MEL 100 response was complete (CR) in 7 and it was VGPR in 9. Mel 100 grade 3-4 toxicity was mainly hematologic, but 15 (36%) required hospital admission for a median of 5 days. The median cost of MEL100 and corresponding supportive therapy was U.S. $2,142.35. In addition, the total median cost of those who needed admission to hospital was U.S. $6,042.78. Thus, pooling costs from patients who needed or did not need admissions the average cost of this strategy was U.S. $3,546.50 per patient. Among Mel 200 patients, except for hematologic toxicity, no patient had greater than grade 2 side effects. On completion of the program, 20 (48%) patients achieved CR, a further 14 (33%) had VGPR, whereas 6 had PR. At a median follow-up of 659 days there were 8 deaths, 1 (2%) was related to the treatment procedures and 6 from disease progression; thus, the 1000 days OS was 73%. Significant adverse factors included older age, lower presentation Hb, and lower Karnofsky %. Nonparametric testing confirmed that good performance scores and VGPR or CR were associated with more favorable outcome. Importantly, these satisfactory results were obtained in the absence of the new biologic cell modifiers. Mel 100 was well tolerated in the outpatient setting and the overall strategy seems to be effective in inducing durable responses with acceptable toxicity.