The Clinical Impact of Thalidomide Maintenance on Progression Free Survival and Postrelapse Survival after Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple myeloma
Authors: Lee Ho Sup , Kim Yang Soo , Min Chang-Ki , Lee Je-Jung , Kim Kihyun , Yoon Dok Hyun , Eom Hyeon Seok , Lee Hyewon , Lee Won Sik , Shin Ho-Jin , Lee Ji Hyun , Park Yong , Jo Jae-Cheol , Do Young Rok , Mun Yeung-Chul 
Published: October 2019

Abstract
Background: There have been many advances in treatments for multiple myeloma (MM). Recently, novel agents such as thalidomide, bortezomib, and lenalidomide have been developed for myeloma treatment. thalidomide was the first novel agent introduced that improved the overall response rate (ORR) and prolonged survival in transplant eligible or ineligible patients with multiple myeloma. It was first confirmed that thalidomide was active in patients with relapsed and/or refractory MM; since then, thalidomide has become an important part of MM treatment, as initial therapy for previously untreated patients, as maintenance therapy following definitive treatment, and as salvage therapy. Until now, the efficacy of thalidomide maintenance has been controversy in some studies. The purpose of this study was estimate necessity of thalidomide maintenance for improving survival in transplantation eligible patients with MM in real clinical fields.
Methods: Data from patients at thirteen university hospitals in South Korea between December 2005 and May 2013 were collected retrospectively. All included patients were treated with induction chemotherapy followed by autologous stem cell transplantation (ASCT) and then with or without maintenance. The included patients were treated with thalidomide based regimens (TD;128 (50.6%), CTD; 96 (37.9%), TAD; 11 (4.3%)), mostly or other conventional regimens such as vincristine, doxorubicin and dexamethasone (VAD; 10 (4.0%), and others; 8 (3.2%)) as induction chemotherapy. And then patients received ASCT. However, patients were excluded underwent tandem ASCT or Allogeneic stem cell transplantation. The number of patients treated with thalidomide maintenance for more than six months after ASCT were 74 (29.2%) without maintenance were 179 (70.8%). The differences of survival were estimated in two groups which were defined to include patients treated with or without thalidomide maintenance. Patients who suffer from progression or relapse after ASCT were received salvage chemotherapy such as bortezomib based or other novel agents based regimen. The progression free survival (PFS) was defined duration from the date of starting induction chemotherapy to the date of disease progression, relapse, or death from any causes after ASCT. The definition of overall survival (OS) was calculated from the date of diagnosis to the date of death from any causes or final follow-up date. The postrelapse survival (PRS) was defined duration from the date of relapse after ASCT to the date of disease progression, relapse, or death from any causes.
Results: The median age of the 253 patients was 57 years (range, 33-75 years) and the male to female ratio was 1.07:1.0. The response rates before ASCT were following: CR or stringent CR (sCR) in 93 (36.7%), VGPR in 63 (24.9%), PR in 86 (34.0%), and < PR in 7 (2.8%). The reason for the higher ORR in this study compared to other studies was that it included patients who were treated with thalidomide induction chemotherapy and who underwent ASCT. Most of these patients achieved more than PR or PR because the South Korean national health insurance only allowed ASCT in such patients. The differences of 3-year PFS of patients with or without maintenance were 66.1% vs 43.0%, p=0.003. The 3-year OS were 91.7% vs 84.5%, p=0.091. And the differences of PRS were not shown in two groups (11.63 vs 10.00 months, p=0.790).
Conclusion: Patients treated with thalidomide maintenance after ASCT were presented higher PFS but not shown higher OS. However, long term use of thalidomide as maintenance therapy was not interfere with efficacy of salvage chemotherapy in patients suffered from progression or relapse after ASCT. So, we suggest that thalidomide maintenance might be useful for improving survival by lowering relapse or progression rates and not interfere with efficacy of salvage chemotherapy in real clinical field. In the future, further prospective studies will be needed to confirm the role of thalidomide maintenance therapy for prolonged survival in patients with MM who are treated with novel agents such as thalidomide, bortezomib, or lenalidomide.

Disclosures
No relevant conflicts of interest to declare.