High-Dose Therapy and Autologous Stem Cell Transplantation for Multiple Myeloma: Analysis from Registry of Monoclonal Gammopathy of Czech Myeloma Group

The role of high-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) in the treatment of Multiple Myeloma (MM) continues to evolve in the era of novel agent. Although data from clinical trials with novel agens are very promising, it is evident that ASCT remains the golden standard for all available patients; moreover combination with proteasome inhibitors and immunomodulatory agens will ensure further benefits and prolongation of overall survival to patients.

To investigate the indication, frequency and results of HDM and ASCT in MM patients in the era of novel agens.

Before inclusion to the Registry of Monoclonal Gammopathy (RMG) of the Czech Myeloma Group (CMG), all persons signed the informed consent forms. Out of 1448 newly diagnosed patients (654 aged≤ 65 years) reported in the RMG in the period 2007–2011, 26.7% (386/1448) underwent ASCT as part of primo therapy. A cohort of 229 patients underwent ASCT as part of the first, second and third relapse (R1–3) treatment in the same time period. Time to progression in different disease settings, objective response rate, and safety were included as exploratory outcomes. Efficacy was assed using the IMWG criteria. A distinctive aspect of this analysis involves comparison of frequency of ASCT during this period of time.

A total of 59% (386/654) of newly diagnosed patients under 65 years underwent ASCT as part of primo therapy. Frequency of indication between patients with age ≤ 65 years was similar (56–63%) during the last five years. Melphalan 200mg/m² was the most frequently used HDM (94%) in primo therapy. The same was true for R1 (73%), R2 (46%) but not R3 where most frequent (49%) HDM was melphalan 100mg/m². Transplant related mortality day+100 ranged between 0.8 to 1.1% during five consecutive years for all treatment settings together and was zero for primo therapy in the year 2007 and 2009–10. Overall responses to ASCT (primo therapy vs. R1 vs. R2 vs. R3) were: ORR 93% (30.5%≥CR) vs. 93% (20%≥CR) vs. 72% (8%≥CR) vs. 54% (4.1%≥CR). Medians of Time to Progression (TTP from the time of ASCT; primo therapy vs. R1 vs. R2 vs. R3) were: 26.2 vs. 15.6 vs. 5.8 vs. 4.8 months and the difference were statistically significant (p<000.1).

ASCT is a safe treatment strategy in MM independently of disease advance, although for patients with more advanced disease, reduced dose of melphalan (100mg/m²) should be considered. ASCT is very effective treatment not only for newly diagnosed MM patients but also for patients in the first relapse. The indication in relapse setting should be considered more frequently than is currently common in the shadow of enthusiasm for novel drugs.

This work was supported by national grants IGA NT12215-4, IGA NT12130-4, GACR P304/10/1395, IGA NT11154-4, MSM 0021622434

Hajek:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees. Spicka:Janssen Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Maisnar:Janssen Cilag: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer (Schering): Honoraria.