A Single Autologous Stem Cell Transplant (ASCT) Followed By Two Years of Post-Transplant Therapy Is Safe in Older Recently Diagnosed Multiple Myeloma (MM) Patients. Preliminary Results from the Prospective Phase II Trial (NCT01849783)

Introduction: The median age at diagnosis of MM patients is around 70. The current standard of treatment for younger eligible MM patients is ASCT after initial induction chemotherapy. Multiple studies have shown that age by itself is not necessarily an exclusion criterion for transplant and that elderly eligible patients derive benefits from ASCT. While melphalan 200mg/m2 has been the standard preparative regimen for ASCT, more studies are currently evaluating the role of including novel agents along with melphalan to improve outcomes. We previously reported the safety and efficacy of VDT-Mel in patients mostly younger than 65 years. Here we report the tolerability of the same regimen in elderly patients.

Methods and patients: A total of 41 eligible patients above the age 65 were prospectively enrolled in the IRB approved phase II trial beginning in June 2013. After an induction chemotherapy and stem cell collection, ASCT was performed with a preparative chemotherapy consisting of VDT-Melphalan 200mg/m2. Early after engraftment, patients were started on maintenance for 2 years with triple agent therapy. Primary end points include PFS, frequency of severe toxicities, ICU admissions, and percentage of patients able to complete the full course of maintenance.

Results: Of the 41 patients enrolled, 37 patients had at least day 100 follow up post-transplantation and were included in this analysis. Six have been removed from study due to relapse (N=2), development of acute leukemia (N=1), failure to collect stem cells (N=1) or failure to comply with therapy (N=2). Toxicity and best response were assessed at day 100. Median age was 68 (range: 65 to 75). Median follow up was 21 months (3.5 months - 3.7 years). Major non-hematologic toxicities ≥ grade 3 were related to infections (25%), diarrhea (16%) and mucositis (11%). Median time to ANC and platelet engraftment was 11 and 17 days, respectively. 18 patients achieved a stringent CR (sCR) by day 100 restaging (50%). There was one death within day 100 related to candida sepsis. Only 2 patients were re-hospitalized within 100 days. Thirty-five patients started maintenance therapy. Median time to start post-transplant therapy was 66 days (range: 42 to 174 days).

Conclusion: This is the first trial to prospectively evaluate the feasibility of combined intensified preparative regimen with two years of maintenance using triple agent therapy in elderly MM patients. Toxicity and mortality were not increased compared to the younger patients (median age 59) receiving a similar regimen. It is too early to comment on the efficacy of this approach, but we are encouraged by the high frequency of sCR, early after transplantation.