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Bending the Curve Trial by Trial
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FIRST

Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma

Phase 3N = 1,623NCT00689936

Population
Patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.
Design
Randomised trial in 1623 patients with newly diagnosed myeloma ineligible for stem-cell transplantation, assigned to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to melphalan-prednisone-thalidomide (MPT) for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT.
Primary endpoint
PFS
Arms
  • Lenalidomide-dexamethasone until progression (Rd continuous) (experimental, n = 535): Lenalidomide plus low-dose dexamethasone in 28-day cycles until progression
  • Lenalidomide-dexamethasone for 18 cycles (Rd18) (experimental, n = 541): Lenalidomide plus low-dose dexamethasone for 72 weeks (18 cycles)
  • Melphalan, prednisone, thalidomide (MPT) (control, n = 547): Melphalan, prednisone and thalidomide for 72 weeks
People
Benboubker L
PFSHR 0.72Δ median PFS+4.3 monthsΔ 48-month OS+8 pointsPFSHR 0.69 (95% CI 0.59–0.79)OSHR 0.78 (95% CI 0.67–0.92)Δ median OS+10 months
Show the numbers
Results reported for FIRST
EndpointAnalysisLenalidomide-dexamethasone until progression (Rd continuous) / Lenalidomide-dexamethasone for 18 cycles (Rd18)Melphalan, prednisone, thalidomide (MPT)Effect
PFSRandomised patients (analysis population not stated in the abstract)primaryBenboubker 2014median 25.5 monthsmedian 21.2 monthsHR 0.72P<0.001Hazard ratio 0.72 is continuous Rd versus MPT (primary comparison); continuous Rd versus Rd18 was 0.70 (P<0.001).
OSRandomised patients (interim analysis)interimBenboubker 201459% at 4 y51% at 4 yGrade 3 or 4 adverse events 70% with continuous Rd versus 78% with MPT.
PFSRandomised patients (final analysis)finalmedian follow-up 67 monthsFacon 2018——HR 0.69 (95% CI 0.59–0.79)P<0.00001Hazard ratio is continuous Rd versus MPT.
OSRandomised patients (final analysis)finalmedian follow-up 67 monthsFacon 2018median 59.1 monthsmedian 49.1 monthsHR 0.78 (95% CI 0.67–0.92)P=0.0023Hazard ratio is continuous Rd versus MPT; the abstract describes median OS with Rd18 as similar (62.3 months).
Results reported for FIRST
EndpointAnalysisLenalidomide-dexamethasone until progression (Rd continuous) / Lenalidomide-dexamethasone for 18 cycles (Rd18)Melphalan, prednisone, thalidomide (MPT)Effect
PFSRandomised patients (analysis population not stated in the abstract)primaryBenboubker 2014median 25.5 monthsmedian 21.2 monthsHR 0.72P<0.001Hazard ratio 0.72 is continuous Rd versus MPT (primary comparison); continuous Rd versus Rd18 was 0.70 (P<0.001).
OSRandomised patients (interim analysis)interimBenboubker 201459% at 4 y51% at 4 yGrade 3 or 4 adverse events 70% with continuous Rd versus 78% with MPT.
PFSRandomised patients (final analysis)finalmedian follow-up 67 monthsFacon 2018——HR 0.69 (95% CI 0.59–0.79)P<0.00001Hazard ratio is continuous Rd versus MPT.
OSRandomised patients (final analysis)finalmedian follow-up 67 monthsFacon 2018median 59.1 monthsmedian 49.1 monthsHR 0.78 (95% CI 0.67–0.92)P=0.0023Hazard ratio is continuous Rd versus MPT; the abstract describes median OS with Rd18 as similar (62.3 months).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.690.59–0.79
OS0.780.67–0.92
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0102030405060Months (modelled)
  • Lenalidomide-dexamethasone until progression (Rd continuous) (experimental)
  • Lenalidomide-dexamethasone for 18 cycles (Rd18) (experimental)
  • Melphalan, prednisone, thalidomide (MPT) (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsLenalidomide-dexamethasone until progression (Rd continuous)Lenalidomide-dexamethasone for 18 cycles (Rd18)Melphalan, prednisone, thalidomide (MPT)
0100.0%100.0%100.0%
1664.7%58.5%59.3%
3241.9%34.2%35.1%
4827.1%20.0%20.8%
6417.6%11.7%12.3%
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%020406080100120140Months (modelled)
  • Lenalidomide-dexamethasone until progression (Rd continuous) (experimental)
  • Lenalidomide-dexamethasone for 18 cycles (Rd18) (experimental)
  • Melphalan, prednisone, thalidomide (MPT) (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsLenalidomide-dexamethasone until progression (Rd continuous)Lenalidomide-dexamethasone for 18 cycles (Rd18)Melphalan, prednisone, thalidomide (MPT)
0100.0%100.0%100.0%
3963.3%64.8%57.7%
7840.1%42.0%33.2%
11725.4%27.2%19.2%
15616.0%17.6%11.1%
Primary publication: Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906-17. PubMedDOI

Appears in

Sources

  1. Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906-17.

    PubMedDOI

  2. Facon T, Dimopoulos MA, Dispenzieri A, Catalano JV, Belch A, Cavo M, et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood. 2018;131(3):301-310.

    PubMedDOI