Paul G. Richardson, MD, Discusses Choosing Between Continuous Lenalidomide Maintenance Vs ASCT in Newly Diagnosed Myeloma

Paul G. Richardson, MD, uses results of the DETERMINATION study that were presented at 2022 ASCO to justify choice of appropriate therapy for individual patients with treatment-naïve multiple myeloma.

At the 2022 American Society of Clinical Oncology Annual Meeting, 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, spoke with CancerNetwork® about the phase 3 DETERMINATION trial (NCT01208662) and how these results will help inform the care of patients with newly diagnosed multiple myeloma. The trial set out to investigate the efficacy of triplet therapy of lenalidomide (Revlimid), bortezomib, and dexamethasone (RVd) followed by continuous lenalidomide maintenance and delayed autologous stem cell transplant (ASCT) vs immediate ASCT.


Patients need choices, and they have to be given options. A one-size-fits-all approach in myeloma no longer applies and the data in our trial support that. Number 1, we see this striking progression-free survival benefit. We see the particular benefit in [patients who are] high-risk, but not always. The population with deletion 17p, for example, did not seem to benefit as much from transplant as other [patients who were] high-risk. Conversely, we showed in certain populations [who received a] transplant that the degree of progression-free survival benefit was not as pronounced, recognizing that many of our studies were essentially hypothesis generating vs definitive because our subset analysis was powered to provide informative rather than definitive information. With all that in mind, we were left with the impression that certain subsets might benefit more than others.

Tolerability issues must be borne in mind. We looked at toxicity comprehensively and we showed that there was a significant drop in quality of life during transplant that fortunately recovered. Nonetheless, in counseling a patient [you must inform them about the] 3- to 4-month period where the quality of life does fall, but it meaningfully recovers. The tolerability profiles between both arms were very much as expected with significantly more toxicity for the transplant group than not. The good news is that these toxicities were manageable. In terms of treatment-related mortality, we saw 1.6% of patients die during the transplant procedure vs just 0.3% on the nontransplant arm, so that was very reassuring. However, we did see a secondary cancer signal. Second primary malignancies were about the same for both groups broadly. We saw significantly more AML/MDS [acute myeloid leukemia/myelodysplastic syndrome] in the transplant arm. We had 10 cases in the transplant early arm vs none in the RVd-alone group. That was important because we need to better understand that getting secondary AML/MDS from treatment is something that we need to minimize at all costs. In that context, we were glad that the events were rare, but nonetheless, they may not be static because this kind of toxicity can increase over time. This is something to watch carefully.


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