Retrospective Analysis Of The Recent Treatment Strategies For The Patients With Myeloma-Related Diseases Registered In Kansai Myeloma Forum
Authors: Tanaka Hirokazu , Kosugi Satoru , Kida Toru , Ohta Kensuke , Yamamura Ryosuke , Shibayama Hirohiko , Kohara Takae , Kaneko Hitomi , Fuchida Shin-ichi , Kobayashi Masayuki , Miyamoto Kazue , Shindo Maki , Kuroda Junya , Uoshima Nobuhiko , Matsumura Yayoi , Yoshii Yumi , Kamitsuji Yuri , Boku Shogen , Ishii Kazuyoshi , Matsuda Mitsuhiro , Takahashi Takayuki , Hamada Tsuneyoshi , Adachi Yoko , Nakatani Eiji , Nomura Shosaku , Taniwaki Masafumi , Takaori Akifumi , Shimazaki Chihiro , Tsudo Mitsuru , Hino Masayuki , Matsumura Itaru , Kanakura Yuzuru 
Published: October 2019

Abstract

Introduction
There has been dramatic evolution in multiple myeloma (MM) therapy in the last decade. The novel agents (Thal, Bor, and Len) have been reported to improve natural history of the cases with MM. In order to use optimal drugs for each patient, we should investigate the actual conditions of the clinical practice. However, we could not have the information regarding epidemiology, clinical features, treatment results, prognosis, and so on because there is no large-scale database demonstrating the clinical features of MM-related diseases in Japan. Therefore, we have founded the study group, named as Kansai Myeloma Forum (KMF), for the purpose of registering the cases with MM-related diseases in Kansai area of Japan on November, 2012.
In this study, we analyzed the clinical characteristics and outcomes of MM-related diseases registered in KMF and evaluated the treatment strategies in the novel agent era.

Patients & Results
Among a total of 923 cases initially diagnosed since 2006 and registered to KMF database until March 31, 2013, we analyzed 434 symptomatic MM cases (213 females/221 males), who were treated since 2006. The median age was 69 (range: 32-96), and the OS rates at 3 and 5 years were 68.7% and 45.3%, respectively. The prognosis of the cases treated after 2010 became significantly better than that of the cases treated between 2006 and 2009 (log-rank test: P=0.019). The prognosis of the cases treated with the novel agents was significantly better than without them (p=0.005). Among the non-transplanted 339 cases, the effects of the novel drugs were shown more clearly (p=0.002). The best response during the course differentiated the prognosis; the hazard ratios of CR, VGPR, PR, SD and PD compared to sCR were 2.23, 3.19, 9.54, 16.84 and 432.01, respectively (P<0.001). Ninety-five cases received the high-dose melphalan therapy (HD-MEL) with stem cell support. The OS rate of these 95 cases was significantly better than that of non-transplanted 339 cases (90.1% at 3-year/61.4% at 5-year vs. 61.6%/40.2%, p<0.001). CR/sCR rate after HD-MEL was 50%. Also, 83 out of 95 cases received at least one of the novel agents during their clinical courses, and 51 cases achieved CR/sCR as best response, showing significant better survival than the cases with best response of VGPR or <PR (p=0.008). The superiority of OS in HD-MEL group was also observed even when less than 65 years old patients (74 out of 95 patients) were compared to 55 patients (≤ 65 years) without HD-MEL but receiving novel agents (90.6% at 3-year/71.4% at 5-year vs. 73.6%/47.3%, p=0.036).
Next, we analyzed 123 cases with MGUS and 54 with smoldering MM (SMM), who had diagnosed in 2006 or later. The median age at diagnosis was 66.0 (range: 34-88) in 123 MGUS cases (53 females/70 males). The type of paraprotein detected was IgA in 15.4% of the cases and IgG in 69.1 %. With a median follow-up period of 27.2 months, 8 cases (6.5%) received chemotherapies due to the disease evolution. The evolution rates at 1, 3 and 5 years after the diagnosis were 2.1%, 9.0% and 12.0%, respectively (2.4% per year). The 3-year OS after the start of treatments was 75.0%. In 54 SMM cases (29 females/25 males), the median age was 68.2 (range: 40-87), and IgG and IgA types comprised 72.2% and 14.8%, respectively. With a median follow-up period of 22.4 months, 15 cases (27.8%) received chemotherapy due to progression to symptomatic MM. The evolution rates at 1, 3 and 5 years after diagnosis were 15.4%, 36.7% and 62.5%, respectively (12.5% per year). The 3-year OS after the start of treatments was 76.9%.

Discussion & Conclusion
The current study revealed the significant effects of novel agents on symptomatic MM cases in the practical use. It has been still unknown and controversial whether HD-MEL with auto-PBSCT is necessary or not in the novel agent era. In this analysis, it was shown that HD-MEL could provide significant survival benefit to symptomatic MM cases even in the novel-agent era. However, it is necessary to determine when and how we should perform HD-MEL for MM during therapeutic sequences including novel agents. This study also suggested that it might be unnecessary to generally consider an early chemotherapy to MGUS or SMM cases before the evolution, since the prognosis after the evolution seemed not to be inferior to that of the de-novo symptomatic MM. Thus, KMF database would provide abundant and beneficial information to consider the treatment strategies of the cases with MM-related diseases.

Disclosures:
Tanaka: celgene: Research Funding. Kosugi:Janssen: Honoraria; celgene: Research Funding. Kida:celgene: Research Funding. Ohta:celgene: Research Funding. Yamamura:celgene: Research Funding. Shibayama:Janssen: Honoraria; celgene: Honoraria, Research Funding. Kohara:celgene: Research Funding. Kaneko:celgene: Research Funding. Fuchida:celgene: Research Funding. Kobayashi:celgene: Research Funding. Miyamoto:celgene: Research Funding. Shindo:celgene: Research Funding. Kuroda:celgene: Research Funding. Uoshima:celgene: Research Funding. Matsumura:celgene: Research Funding. Yoshii:celgene: Research Funding. Kamitsuji:celgene: Research Funding. Boku:celgene: Research Funding. Ishii:celgene: Research Funding. Matsuda:celgene: Research Funding. Takahashi:celgene: Research Funding. Hamada:celgene: Research Funding. Adachi:celgene: Research Funding. Nakatani:celgene: Research Funding. Nomura:celgene: Research Funding. Taniwaki:celgene: Research Funding. Takaori:celgene: Research Funding. Shimazaki:celgene: Research Funding. Tsudo:celgene: Research Funding. Hino:celgene: Research Funding. Matsumura:Janssen: Honoraria, Research Funding; celgene: Research Funding. Kanakura:celgene: Research Funding.