Age under 40 Does Not Confer Superior Prognosis in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transplant Despite High Response Rates.

BACKGROUND: Multiple myeloma (MM) only occurs in 2% of patients under the age of 40. It has been reported that this young cohort of patients have a superior overall survival when compared to those over the age of 40.

OBJECTIVE: To evaluate the clinical and laboratory features of patients ≤40 years of age at diagnosis of MM and to compare survival outcomes to patients >40 years of age.

METHODS: Retrospective institutional review of all patients ≤40 years of age at time of diagnosis of MM that had underwent upfront ASCT at PMH from January 1, 1990 to July 31, 2007. Outcomes were compared to patients >40 years of age who had also undergone ASCT as upfront therapy.

RESULTS: 37 patients ≤40 years of age were identified. Twenty patients were male. Immunoglobulin subtype was as follows: 49% had IgG, 19% light chain,16% IgA, 8% IgD, and 5% IgG plasma cell leukemia. The main presenting clinical feature was bone pain (63%). 73% had radiological evidence of bony disease at diagnosis and 53% of these patients required radiation prior to ASCT. Clinical features included anemia in 81%, renal insufficiency in 39% and hypercalcemia in 28%. Conditioning regimens for ASCT were high dose melphalan (200mg/m²) alone in 25 pts, VP-16 & melphalan +/− TBI in 8 pts, bleomycin & cyclophosphamide in 3 pts, and in 1 pt it was unknown. Median time to engraftment of neutrophils (>0.5 x 10⁹/L) and platelets (>20 x 10⁹/L) was 11 days (range 8–18) and 12 days (range 0–54), respectively. Median duration of hospitalization was 17 days (range 10–54). No treatment related mortality was experienced. Response to ASCT was as follows in 29 evaluable pts: CR in 10 (34.5%), PR in 13 (44.8%), MR in 1 (3.4%), SD in 3 (10.3%), and PD in 2 (6.9%). Five patients underwent a tandem ASCT. Maintenance therapy was instituted in 11 pts. Median progression free survival (PFS) post ASCT was 23.0 months, which is similar to the PFS of 28.5 months in patients over 40 (p=0.559). There was also no difference in median overall survival (OS) from date of ASCT between the two groups (6.6 years in pts ≤40, 6.7 years in pts >40; p=0.797).

CONCLUSION: Young patients with MM present with advanced disease as evidenced by anemia, bone involvement and hypercalcemia. ASCT yields high response rates, but PFS post ASCT is less than 2 years. Although young age has been historically been considered to be a positive prognostic marker, OS post ASCT is only 6.6 years, which is equivalent to those >40 years of age. Strategies to better the outcomes of young patients with MM are required.