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Clinical Trial
. 2020 Jul;34(7):1875-1884.
doi: 10.1038/s41375-020-0711-6. Epub 2020 Jan 30.

Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Nizar J Bahlis  1 , Meletios A Dimopoulos  2 , Darrell J White  3 , Lotfi Benboubker  4 , Gordon Cook  5 , Merav Leiba  6 , P Joy Ho  7 , Kihyun Kim  8 , Naoki Takezako  9 , Philippe Moreau  10 , Jonathan L Kaufman  11 , Maria Krevvata  12 , Christopher Chiu  12 , Xiang Qin  12 , Linda Okonkwo  13 , Sonali Trivedi  12 , Jon Ukropec  14 , Ming Qi  12 , Jesus San-Miguel  15
Affiliations
Clinical Trial

Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Nizar J Bahlis et al. Leukemia. 2020 Jul.

Abstract

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1-21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35-0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10-5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31-0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42-0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

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Conflict of interest statement

NJB consulted for and received honoraria and research funding from Janssen, Celgene, and Amgen. MAD consulted for and received honoraria from Janssen, Celgene, Takeda, Amgen, and Bristol-Myers Squibb. DJW received honoraria from and served on advisory committees for Amgen, Celgene, Janssen, and Takeda. GC received honoraria from Amgen, Bristol-Myers Squibb, GlycoMimetics, Celgene, Janssen, Takeda, and Sanofi; and received research funding from Celgene, Janssen, and Takeda. PJH received honoraria from Janssen, Amgen, Novartis, and Takeda; and received travel support from Takeda and Celgene. PM received honoraria from and served on advisory committees for Amgen, Celgene, Janssen, Takeda, and AbbVie. JLK served in a consulting or advisory role for Janssen, Celgene, Takeda, Amgen, and Sanofi Genzyme; and received research funding from Janssen, Bluebird, Bristol-Myers Squibb, Celgene, and Sutro Biopharma. MK, CC, XQ, LO, ST, JU, and MQ are employees of Janssen. JS-M received honoraria from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Novartis, Sanofi, and Roche. LB, ML, KK, and NT have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. PFS in the ITT population and in patient subgroups based on prior treatment.
PFS in (a) the ITT populationa and in patients with (b) one prior line of therapy, (c) responses of CR or better, (d) prior lenalidomide exposure, or (e) refractoriness to bortezomib. Kaplan–Meier estimates of PFS. PFS, progression-free survival; ITT, intent-to-treat; D-Rd, daratumumab/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone; HR, hazard ratio; CI, confidence interval; NE, not estimable. aThe upper bound of the 95% CI is currently NE.
Fig. 2
Fig. 2. PFS in patient subgroups.
PFS, progression-free survival; D-Rd, daratumumab/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone; CI, confidence interval; NE, not estimable; ISS, International Staging System; MM, multiple myeloma; Ig, immunoglobulin; ECOG, Eastern Cooperative Oncology Group; CrCl, creatinine clearance; PI, proteasome inhibitor; FISH, fluorescence in situ hybridization. aImpaired hepatic function included mild, moderate, and severe hepatic dysfunction as per National Cancer Institute organ dysfunction criteria. bCytogenetic risk was determined by FISH or karyotyping. cPatients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities.
Fig. 3
Fig. 3. PFS based on MRD status (10–5).
PFS, progression-free survival; MRD, minimal residual disease; D-Rd, daratumumab/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone.
Fig. 4
Fig. 4. Time to subsequent therapy and PFS2.
Time to subsequent therapy (a) and PFS2 (b) in the ITT population. PFS2, progression-free survival on subsequent line of therapy; HR, hazard ratio; CI, confidence interval; Rd, lenalidomide/dexamethasone; D-Rd, daratumumab/lenalidomide/dexamethasone; ITT, intent-to-treat.
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References

    1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™. Multiple Myeloma. Version 1.2019. 2018. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed 19 Oct 2018.
    1. Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv52–iv61. doi: 10.1093/annonc/mdx096. - DOI - PubMed
    1. de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840–8. doi: 10.4049/jimmunol.1003032. - DOI - PubMed
    1. Lammerts van Bueren J, Jakobs D, Kaldenhoven N, Roza M, Hiddingh S, Meesters J, et al. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79. Blood. 2014;124:3474. doi: 10.1182/blood.V124.21.3474.3474. - DOI
    1. Overdijk MB, Verploegen S, Bogels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7:311–21. doi: 10.1080/19420862.2015.1007813. - DOI - PMC - PubMed

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