Paul G. Richardson, MD, Talks Rationale for Investigating Lenalidomide Maintenance Until Progression in Newly Diagnosed Myeloma


At 2022 ASCO, Paul G. Richardson, MD, reviewed the rationale of the phase 3 DETERMINATION study that set out to determine the benefit of lenalidomide maintenance with or without autologous stem transplantation in newly diagnosed multiple myeloma.

CancerNetwork® spoke with Paul G. Richardson, MD, clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute as well as RJ Corman Professor of Medicine at Harvard Medical School, both in Boston, Massachusetts, about the rationale behind deciding the utility of continuous lenalidomide (Revlimid) maintenance following triplet therapy in patients with newly diagnosed multiple myeloma in the phase 3 DETERMINATION trial (NCT01208662) that was presented at the 2022 American Society of Clinical Oncology Annual Meeting.1


The rationale for the DETERMINATION study was built on the success of the triplet novel therapy combinations in upfront, newly diagnosed patients [with multiple myeloma]. What we showed with combinations such as lenalidomide, bortezomib, and dexamethasone—RVd—was that we generated high response rates, between 90% and 100%, and high-quality response rates with complete responses in up to 50% of patients. With that kind of efficacy from the RVd triplet and other combinations like it, a key question [regarding] younger transplant-eligible patients [surrounds] how transplant is best integrated into that approach.

DETERMINATION sought to do several things. First and foremost, it was to evaluate RVd with either early transplant or deferred transplant. The second thing was to look at the real impact of lenalidomide maintenance until progression because we have data both here in the United States and overseas suggesting that lenalidomide maintenance matters. The key question was, how much is enough and how long should it be given? Given that fact, our own data from the CALGB-100104 study [NCT00114101] and the Alliance suggested that we should continue [lenalidomide] until progression. Our European partners, in particular, the IFM [International Myeloma Foundation], ran a parallel study [NCT01191060] which was a tremendous collaborative effort but was under regulatory pressures requiring only 1 year of lenalidomide.2 They conducted their study identical to ours, but with just 1 year of maintenance. We conducted our study with the key difference being maintenance until progression.


  1. Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): The phase 3 DETERMINATION trial. J Clin Oncol. 2022;40(suppl 17):LBA4. doi:10.1200/JCO.2022.40.17_suppl.LBA4
  2. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/NEJMoa1611750
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