Addition of Low-Dose Decitabine to Bortezomib and Dexamethasone in Multiple Myeloma at First Relapse

Letter to Editor

Dear He,

Please find a manuscript entitled “Addition of low-dose decitabine to bortezomib and dexamethasone in multiple myeloma at first relapse” by Ning Li, Lijie Liang, Yuzhang Liu, Pu Xiang, Yaomei Wang, Suxia Luo, Yongping Song, and Baijun Fang for your consideration for publication in Annals of Hematology & Oncology.

For patients with Relapsed or Refractory Multiple Myeloma (RRMM), the second-line therapy is particularly important. However, there is no clear consensus regarding the best second-line therapy for RRMM until now. Recently, some large randomized studies have reported a subgroup analysis of first-time relapsed patients receiving daratumumab, elotuzumab, pomalidomide, panobinostat, or carfilzomib-based triple regimens, and the results were very dramatic. Unfortunately, access to and affordability of abovementioned novel drugs pose a major challenge, both in China and around the world. In addition, optimal combination treatments must target simultaneously both the myeloma and its interactions with microenvironment. Furthermore, bortezomib- and/or lenalidomidebased triplet combinations are the most common first-line and maintenance regimens for newly diagnosed MM patients in China at present and in the next few years, which leads to the urgent need for effective therapies for bortezomib and/or lenalidomide refractory patients. Therefore, the screening of available and inexpensive agents, aiming at synergizing with other established affordable antimyeloma agents and targeting simultaneously the MM clone itself and the MM immune microenvironment remains a high priority in many parts of the world, including China.

We conducted a single-center, open-label phase 2 study to evaluate the activity and safety of low-dose decitabine plus bortezomib and dexamethasone (DVd) as second-line therapy in patients with RRMM. Results from this trial showed that DVd induced deep and durable responses with a favorable safety profile, regardless of previous treatment or baseline characteristics. The data of ORR, CR or better, VGPR or better, median PFS, and 12- and 18-month PFS rates are even comparable to that from CASTOR trial when the analysis is restricted to RRMM patients with only one prior line of therapy.

In conclusion, the addition of low-dose decitabine to bortezomib and dexamethasone proved to be a well-tolerated and highly costeffective triplet regimen for RRMM at first relapse, leading to high quality responses irrespective of previous treatment or baseline characteristics, it may represent a good option for patients after frontline lenalidomide and/or bortezomib treatment.

The procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration.

We confirm the material is original research which has not been previously published and has not been submitted for publication elsewhere while under consideration.

We confirm that all authors fulfill all conditions required for authorship. We also confirm that there is no potential conflict of interest or financial dependence regarding this publication, as described in the Instruction for Authors. All authors have read and approved the manuscript.

We sincerely hope that you find this manuscript of sufficient scientific merit for publication in Annals of Hematology & Oncology.

Yours sincerely

Baijun Fang