Assessment, Analysis, and Discussion
multiple myeloma, SWOG
MULTIPLE MYELOMA
In this phase II trial, we found that response rates and survival with oral metronomic cyclophosphamide, ixazomib, and dexamethasone for patients with newly diagnosed multiple myeloma were below those seen in other studies using similar drugs. In our study only 16.7% of patients obtained a VGPR and 58.3% of patients a PR or better (Response rates and survival are also superior in other standard of care options for front-line treatment for multiple myeloma. In patients who received RVD in the SWOG S0777 trial 27.8% of patients and 81.5% of patients achieved a VGPR or PR or better, respectively.There are several possible reasons for the low response rate and worse survival seen in our study. Metronomic cyclophosphamide may be inferior to standard weekly cyclophosphamide dosing, especially in the newly diagnosed setting. Metronomic cyclophosphamide has been evaluated in several studies; however, its efficacy has largely been seen in the relapsed/refractory setting.Several other factors may have also limited the efficacy evaluation of our study. Enrollment to the study was limited by several factors and we did not reach our goal of 20 patients for full efficacy evaluation. Study enrollment was started in August 2015 and between initial protocol development and first cohort enrollment several studies have been published showing the efficacy of alternative treatment options. These include phase I/II data of carfilzomib-lenalidomide–dexamethasone (KRd) in 2015, the formal the publication of the SWOG S077 data in 2017, and the addition or substitution of daratumumab to the backbone of RVD as early as 2019.While our sample size was limited our data do not suggest benefit of further study of this specific drug regimen in the first-line setting except in unique patient populations that may not be able to tolerate alternative treatment options. Given the larger patient size in the Dimopoulos et al. study (of all oral weekly cyclophosphamide, ixazomib, and dexamethasone) and the improved response rates it would suggest that an all-oral therapy with weekly cyclophosphamide as opposed to metronomic dosing could be considered.