Ola Landgren, MD, PhD, Highlights How DETERMINATION Trial Results Inform Use of RVd/Transplant in Newly Diagnosed Myeloma

C. Ola Landgren, MD, PhD, a professor and leader of Experimental Therapeutics and Myeloma Service at the Sylvester Comprehensive Cancer Center, University of Miami Health System, in an interview with CancerNetwork^® highlighted key efficacy findings from the phase 3 DETERMINATION trial (NCT01208662) assessing the use of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) plus autologous stem cell transplant vs RVd alone, both with continuous lenalidomide maintenance, in patients with newly diagnosed multiple myeloma.¹ Moreover, he highlights how the findings compare with similar research such as the phase 3 IFM/DFCI2009 trial (NCT01191060) which previously assessed RVd alone or with high-dose transplant followed by 1 year of lenalidomide maintenance in newly diagnosed multiple myeloma.²

Patients treated on DETERMINATION who received RVd alone had a median progression-free survival (PFS) of 46.2 months compared with 67.5 months in the transplant group (HR, 1.53; 95% CI, 1.23-1.91; P <.0001). The rates of partial response or better were 95.0% and 97.5% in each respective group. No overall survival benefit was noted in either arm (HR, 1.10; 95% CI, 0.73-1.65; P = .99).

Transcript:

The DETERMINATION study showed very similar [findings to the phase 3 IFM/DFCI2009 trial in] that there is a progression-free survival benefit following bone marrow transplant; it was found to be around 21 months. That’s a quite long time. But also, they showed that there is no survival difference [between the 2 treatment arms]. The follow-up time is only around 5 years in the DETERMINATION trial, which is slightly shorter [than IFM/DFCI2009] but confirms very similar results.

Another very important difference between the 2 studies was that in the DETERMINATION study, of the patients on the non-transplant arm [who progressed], a much lower proportion of those patients went to transplant [vs IFM/DFCI2009]. In the DETERMINATION study, it was in the range of 20% to 25% while in the IFM/DFCI2009 study it was 70% to 80%. Despite the fact that there were fewer patients who went to transplant at the time of relapse in the non-transplant up-front arm, you still see no survival difference. Of course, this raises the question [as to whether] you need to do a transplant upfront, do you need to delay it, or do you never need to do the transplant?

This is exactly what Joseph Mikhael, MD, [of the Translational Genomics Research Institute], talked about as the discussant at ASCO. He made a very good, balanced, and fair evaluation when he said that you can make a case for transplant. If you want to extend PFS, you can make a case against the transplant not showing survival difference. There were a lot of other nuances, [such as] the onset of second malignancies. There were 10 cases of [acute myeloid leukemia and myelodysplastic syndrome] in the transplant arm and none in the non-transplant arm. There were quality-of-life differences in favor of no transplant; patients had several months of worsening as expected of their quality of life [following] transplant. Mikhael summarize saying, “Welcome to the future of myeloma—the era of choice. It is no longer mandatory for patients to do transplant.” And I agree with that.

References

1. Richardson PG, Jacobus SJ, Weller EA, et al. DETERMINATION Investigators. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. Published online June 5, 2022. doi:10.1056/NEJMoa2204925
2. Attal M, Lauwer-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2022;376(14):1311-1320 doi:10.1056/NEJMoa1611750