During a Case-Based Roundtable® event, Laahn Foster, MD, discussed the SWOG S0777 and MAIA trials in transplant-ineligible newly diagnosed multiple myeloma in the second article of a 2-part series.
Targeted Oncology: What is the role of RVd (lenalidomide [Revlimid], bortezomib [Velcade], and dexamethasone) in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM)?
Laahn Ho Foster, MD: RVd is an excellent regimen based on the SWOG S0777 study [NCT00644228], looking at RVd vs Rd [lenalidomide plus dexamethasone].1 The way that RVd was used was for 8 cycles, basically 6 months, and then it was followed by Rd maintenance. The Rd [arm] was just Rd [for 6 cyles of 28 days] and then was continued on a maintenance schedule. We could see the difference in how patients responded to RVd vs Rd. [At median follow-up of 84 months], they did better on RVd with a median progression-free survival [PFS] of 41 months vs 29 months with Rd [HR, 0.742; 96% CI, 0.594-0.928; P = .003].1
And [for overall survival (OS)] they have a separation of results [HR, 0.709; 96% CI, 0.543-0.926; P =.0114].1 The thing about this study is that this was a younger population. The difference between this and the MAIA study [NCT02252172], is that the patients in the study were younger, [many of whom were] less than the age of 65. The Kaplan-Meier curves show how they did and the patients who were older than 65 tended to do worse [with a median PFS of 65 months in those 65 or older vs not reached in those younger than 65 years old].1
What adverse events are of most concern with RVd, and what has been done to mitigate them?
The neuropathy is a concern. With this regimen no one uses bortezomib twice weekly at this point. There was a lot of neuropathy [on the trial], but going down to the once weekly dosing of bortezomib has mitigated that risk.2
RVd-lite is a modification of how RVd is given.3 They’ve extended the cycles of it, so instead of [lenalidomide being given on the first] 21 days and [bortezomib] twice weekly, you’re getting weekly bortezomib and a lower dose of lenalidomide [(15 mg vs 25 mg) on a 35-day cycle].2
What other option is available for treating newly diagnosed multiple myeloma in patients not intended to receive a stem cell transplant?
The other option [for these patients] is dara-Rd [daratumumab (Darzalex), lenalidomide, and dexamethasone] supported by the MAIA study, looking at dara-Rd vs Rd. Again, just note that this is an older population with a median age of 73 years old [vs 63 years in the SWOG S0777 study].2,4
The overall response rates [in the MAIA study] were over 90% for dara-Rd, 93% vs 82% for Rd, and the depth of response [was demonstrated by] the complete response (CR) rate [which showd] more than 51% achieved a CR or better, and that’s compared with approximately 30% for the Rd arm.5 The minimal residual disease negativity rates show it was approximately 32% for dara-Rd vs 11% for Rd.
[Further], the PFS is significantly longer with the dara-Rd [HR, 0.55; 95% CI, 0.45-0.67; P < .0001], and it also looks like there’s an OS benefit in these patients who are treated with dara-Rd vs Rd [HR, 0.65; 0.52-0.80; P < .0001].6
What impact did daratumumab have on the toxicities these patients experienced?
It didn’t seem that the addition of daratumumab changed the safety profile [of the therapy] all that much.4,7 There was a little bit more in terms of cytopenias that you’ll notice, and there was a bit more in terms of diarrhea [57% any-grade with dara-Rd vs 46% any-grade with Rd].
What additional analyses of the MAIA data give insight into the use of dara-Rd?
[In a post hoc analysis] we can see the outcomes in frail patients on dara-Rd. They separated [patients by] whether they were frail vs not frail. The patients who were not frail, as you would expect, did better than the patients in the frail cohort [with a HR of 0.48 favoring dara-Rd in the non-frail cohort and a HR of 0.62 favoring dara-Rd in the frail cohort].8
We can see the differences in how patients did in the younger group vs the older group for PFS [in those] less than 75 years old [with a 60-month PFS rate of 57.4% for dara-Rd vs 33.6% for Rd], and in those patients less than 70 years old [with a 60-month PFS rate of 67.2% vs 28.7%, respectively].8 There are separations [between] how patients did with dara-Rd vs Rd, and of course, the patients who were younger seemed to do better than the older subgroup.
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