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H.W. Auner et al. A
B
C
Figure 4. Survival and relapse risk by cytogenetic risk. (A) Overall survival, (B) progression-free survival and (C) relapse risk estimates and confidence intervals at 2 years after ASCT are shown for patients with high-risk or standard-risk chromosomal abnormalities.
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ties should aid optimal selection of both younger and older patients.36-40
The CALM study is based on the retrospective analysis of registry data that were collected in a defined cohort of patients. Thus, the choice of Mel140 or Mel200 was made by transplant physicians and influenced or determined by local practice, thereby introducing a potential for biased treatment decisions. The paucity of data on post-trans- plant treatments, including maintenance, is another limita- tion of the analysis. However, the large number of patients from multiple centers across Europe is likely to have formed a representative ‘real-world’ sample of myeloma patients undergoing up-front ASCT. This notion is supported by the distribution of baseline clinical and cytogenetic features and the outcomes of patients with high-risk compared to standard-risk disease. Moreover, we applied robust statistical methods for the estimation of hazard ratios.
Our data indicate that the vast majority of patients undergoing upfront ASCT in a real-world setting receive Mel200 conditioning, and that patients with poor clinical responses to induction therapies derive more benefit from
Mel200 than from Mel140. However, the results of this study also indicate that transplantation in very good par- tial response/complete response may favor Mel140 over Mel200. While the reasons for this unexpected finding remain to be determined, the data raise the challenging question of whether more patients should receive Mel140. This is relevant given that modern induction regimens achieve high very good partial response/complete response rates. The data presented here suggest that a ran- domized trial to define the optimal melphalan dose is war- ranted. Such a trial could also investigate the use of alter- native conditioning approaches that incorporate novel agents41-44 and the potential role of melphalan dosing in tandem transplant approaches, which was not feasible in this analysis. In the meantime, although Mel200 should remain the standard of care for ASCT conditioning, Mel140-based transplants could be considered as a valid alternative to offer patients an effective combination of ASCT plus novel therapies.45
In conclusion, our findings indicate that remission status at the time of a first ASCT may need to be considered when deciding the melphalan dose.
References
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Child JA, Morgan GJ, Davies FE, et al. High- dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875-1883. Palumbo A, Cavallo F, Gay F, et al.
Autologous transplantation and mainte- nance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895-905.
4. Gay F, Oliva S, Petrucci MT, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus
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