Lenalidomide Versus Thalidomide or Bortezomib As Maintenance Regimens for Non-Transplant Patients with Multiple Myeloma: Multi-Center Real World Experience in China
Authors: Zhuang Zhe , Shi Lei , Tian Ying , Zou Dongmei , Feng Ru , Dong Fei , Ma Yanping , Yu Hong , Tian Wei-wei , Liu Shuangjiao , Ma Liangming , Fu Rong , Jing Hongmei , Liu Hui , Sun Wanling , Wenming Chen , Wu Yin , Bao Li , Zhuang Junling 
Published: November 2021

Abstract
Background
Maintenance (MT) after front-line therapy is the current standard for multiple myeloma (MM). However, no adequate data has shown the present situation of maintenance treatment in China yet, and autologous stem cell transplantation (ASCT) rate is still low in eligible newly diagnosed MM (NDMM) patients. Hence, we conducted this retrospective real-world study on efficacy and safety of the mainstream maintenance regimens in non-transplant NDMM patients-thalidomide (T-MT), lenalidomide (L-MT) and bortezomib (B-MT).
Methods
Clinical data were collected from 9 centers of North China MM Registry, during January 2010 to December 2020. The progression-free (PFS) and overall survival (OS) from maintenance, and drug toxicities were compared in T-MT, L-MT and B-MT groups. Thalidomide 75-150mg/day was administrated in T-MT group. L-MT group received lenalidomide as 25mg every other day or 10mg daily, on day 1-21 of a 28-day cycle. Bortezomib (1.3 mg/m 2 s.c.) was administered every other week or 4 vials every 3 months. Dexamethasone was given along with L or B in some patients.
Results
A total of 355 patients were enrolled including 159 in T-MT, 143 in L-MT and 53 in B-MT. At baseline, the gender ratio, paraprotein isotype, ISS and R-ISS stage, as well as response status before MT were comparable. Patients on L-MT were significantly older than the other groups. Meanwhile, greater proportions of patients in L-MT and B-MT groups had high-risk cytogenetic abnormalities (HRCA), defined as amplification 1q21 (1q21+), deletion 17p (17p-), t(4,14), t(14,16).
The median follow-up duration since maintenance was 40.1, 19.6 and 22.2 months (m) in T-MT, L-MT and B-MT groups, respectively. There were 67.9%, 61.5% and 60.4% patients with T-MT, L-MT and B-MT achieving very good partial response (VGPR) or better before maintenance. Disease progression was recorded in 101 patients (63.5%) with T-MT, 54 (37.5%) with L-MT and 19 (35.8%) with B-MT. While mortality was 46 (28.9%), 22 (15.3%) and 4 (7.5%), respectively. The median PFS was 23m in T-MT, as compared with 26.9m in L-MT and 37.0m in B-MT (p=0.59). Median OS was 91.0M in T-MT, whereas not reached (NR) in the others (p=0.50).
Patients reached complete response (CR) or stringent CR (sCR) before MT had prolonged PFS compared to those with VGPR or less in T-MT (28.0m vs 17.0m, p=0.06) and L-MT group (27.4m vs 18.2m, p=0.02), while comparable in B-MT (NR vs 30.8m, p=0.25). Meanwhile, patients in each group had similar OS despite of different responses before MT.
Patients with 1q21+ on T-MT had shorter median PFS compared to those without (12.2m vs 21.0m, p=0.08), as well as impaired median OS (53.1m vs 81.0m, p= 0.004), despite various second line therapies. While the PFS of L-MT was 26.9m for patients with 1q21+ and 27.4months for those without (p=0.99). In B-MT group, the PFS was 43.5m and 30.2m (p=0.64), respectively. Median OS was not reached in both L-MT and B-MT.
Only a few patients with 17p- in T-MT and B-MT, yet also presented remarkably inferior PFS (7.0m vs 21.0m, p=0.011) and OS (32.0m vs 81.0m, p=0.001) with thalidomide. As for L-MT, PFS (22.2m vs 27.4 m, p=0.19) and OS (NR vs NR, p=0.55) were not of discrepancy between 17p- or without. In B-MT, PFS (30.8m vs NR, p=0.99) was similar, though median OS was not reached, inferior tendency was observed (p= 0.04).
As for patients with any adverse CA, T-MT resulted in impaired PFS (12.0m vs 23.0m, p=0.02) and OS (53.0m vs NR, p＜0.01). In contrast, PFS and OS were both comparable in patients with L-MT or B-MT no matter with HRCA or not.
The main reason of maintenance withdrawal was disease progression. Among patients with detailed records of adverse effects, adverse event related discontinuation was seen in 5.3%(n=5), 6.1%(n=3) and 0 patients in T-MT, L-MT and B-MT, respectively.
Conclusions
In this multi-centered real-world maintenance study, thalidomide, lenalidomide or bortezomib after front-line therapy in non-transplant NDMM patients has similar PFS and OS. However, patients on L-MT and B-MT have greater proportion of HRCAs, which drags down survival in T-MT especially with 1q21+ and 17p-, while L-MT and B-MT mostly reverses the negative effects. Clinicians in the real practice prefer to select lenalidomide or bortezomib as maintenance in patients with HRCAs, while thalidomide is still an option for patients with standard risk.
Figure 1. A) Baseline characteristics in three groups. * p＜ 0.05. B) PFS of the three groups. C) OS of the three groups.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.