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28 januari 2026: Bron: FDA o.a.

Wanneer daramutumab (Darazalex)  en hyaluronidase-fihj (Darzalex Faspro) in combinatie met bortezomib (Velcade), lenalidomide (Revlimid) en dexamethason als behandeling wordt gegeven bij patiënten met een eerste diagnose van Multiple Myeloma (botkanker, ziekte van Kahler) die niet in aanmerking komen voor een autologe stamceltransplantatie dan blijkt de ziekteprogressievrije tijd en overall overleving aanzienlijk beter dan met alleen daramutumab (Darazalex) aanvullend op bortezomib (Velcade), lenalidomide (Revlimid) en alleen dexamethason in de combinatiebehandeling.

De resultaten uit de fase 3 studie CEPHEUS zijn, vertaalt in het Nederlands:

In de daramutumab (Darazalex)  en hyaluronidase-fihj (Darzalex Faspro) groep bedroeg de mediane behandelingsduur 56,3 maanden (bereik: 0,1-64,6) versus 34,3 maanden (bereik: 0,5-63,8) met alleen dexamethason in de combinatiebehandeling.²
Bij patiënten in de daramutumab (Darazalex)  en hyaluronidase-fihj (Darzalex Faspro) groep met een complete respons (CR) of beter (n = 150) was het percentage MRD-negativiteit  68,7% (95% betrouwbaarheidsinterval: 60,6%-76,0%).
Bij patiënten in de controlegroep die een complete respons (CR) of beter bereikten (n = 116) was dit percentage 59,5% (95% betrouwbaarheidsinterval: 50,0%-68,5%).
De percentages aanhoudende MRD-negativiteit  in deze respectievelijke groepen waren 42,6% versus 25,3% (p = 0,0003).
In de daramutumab (Darazalex)  en hyaluronidase-fihj (Darzalex Faspro) groep was de objectieve responsratio (ORR) 97,0%, inclusief strikte complete respons (sCR's; 65,0%), complete respons (CR's; 16,2%), zeer goede partiële responsen (VGPR's; 11,7%) en partiële responsen (PR's; 4,1%).
In de groep met alleen daramutumab (Darazalex) was de ORR 93,4%, inclusief sCR's (44,9%), CR's (16,7%), VGPR's (24,7%) en PR's (7,1%).

Op basis van deze resultaten heeft de FDA - Food and Drug Administration deze behandeling goedgekeurd om als eerstelijns behandeling te gebruiken bij deze groep van patiënten. Zie dit artikel op de website van de FDA.

Eerder werden de resultaten van de fase III studie CEPHEUS gepubliceerd:

Erratum in

Abstract

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10-5 by next-generation sequencing. Major secondary endpoints included complete response (CR) or better (≥CR) rate, progression-free survival and sustained MRD-negativity rate at 10-5. At a median follow-up of 58.7 months, the MRD-negativity rate was 60.9% with D-VRd versus 39.4% with VRd (odds ratio, 2.37; 95% confidence interval (CI), 1.58-3.55; P < 0.0001). Rates of ≥CR (81.2% versus 61.6%; P < 0.0001) and sustained MRD negativity (≥12 months; 48.7% versus 26.3%; P < 0.0001) were significantly higher with D-VRd versus VRd. Risk of progression or death was 43% lower for D-VRd versus VRd (hazard ratio, 0.57; 95% CI, 0.41-0.79; P = 0.0005). Adverse events were consistent with the known safety profiles for daratumumab and VRd. Combining daratumumab with VRd produced deeper and more durable MRD responses versus VRd alone. The present study supports D-VRd quadruplet therapy as a new standard of care for transplant-ineligible or transplant-deferred NDMM. ClinicalTrials.gov registration: NCT03652064 .

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Conflict of interest statement

Competing interests: S.Z.U. received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDx and Takeda and consulted for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Edo Pharma, Genentech, Gilead, GSK, Janssen, Oncopeptides, Sanofi, Seattle Genetics, Secura Bio, SkylineDx, Takeda and TeneoBio. V.H. received honoraria for lectures/advisory boards from AbbVie, Amgen, Bristol Myers Squibb, GSK, Johnson & Johnson, Pfizer, Regeneron, Sanofi and Takeda. N.J.B. consulted for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, GSK, Genentech, Karyopharm Therapeutics, Kite, Novartis, Pfizer, Roche, Sanofi and Takeda, received research funding from Janssen and Pfizer and honoraria from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, GSK, Genentech, Karyopharm Therapeutics, Kite, Novartis, Pfizer, Roche, Sanofi and Takeda and served on the Board of Directors or advisory committees for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, GSK, Genentech, Karyopharm Therapeutics, Kite, Novartis, Pfizer, Roche, Sanofi and Takeda. C.P.V. received honoraria from Janssen, Bristol Myers Squibb, GSK, Sanofi, Pfizer, AbbVie and Forus. M. Braunstein participated in speakers bureaus for Bristol Myers Squibb, Janssen, Takeda and Sanofi. J.M.M. served as a consultant for Bristol Myers Squibb, Medison Pharma, Pfizer and Roche. Y.C.C. served as a consultant for, received research funding and honoraria from and served on the Board of Directors or advisory committees for Bristol Myers Squibb, Janssen, Takeda, Sanofi and GSK. M.M. received honoraria from Janssen Pharmaceuticals, Ono Pharmaceutical, Takeda Pharmaceuticals, Sanofi K.K. Nippon Kayaku and SymBio Pharmaceuticals and received research funding from Janssen Pharmaceuticals, Bristol Myers Squibb K.K., GSK and Pfizer. K.S. received lecture fees from Takeda, Ono Pharmaceutical, Novartis, Sanofi, Bristol Myers Squibb and Janssen and received advisory fees from SRL. M. Beksac served as a consultant for Bristol Myers Squibb, Takeda, Janssen, Menarini, Amgen and GSK and participated in speakers bureaus for Bristol Myers Squibb, Janssen, Takeda and Sanofi. A.M. served as a consultant for Janssen, Takeda, Amgen, Bristol Myers Squibb, Sanofi, Novartis, AstraZeneca, Pfizer and AbbVie and received honoraria from Janssen, Takeda, Amgen, Bristol Myers Squibb, Sanofi, Novartis, AstraZeneca, Pfizer and AbbVie. H.T. served as a consultant for SRL, received honoraria from Janssen, Ono Pharmaceutical, Sanofi and Bristol Myers Squibb and received research funding from Bristol Myers Squibb. A.P. received research funding from Bristol Myers Squibb, Sanofi and Takeda. T.A. is an employee of Genmab and owns stock. W. Liu, J.W., K.C., J.V., M.K., L.L.-M., J.C., M.R. and R.C. are employees of Janssen. S.Z. received research funding from Janssen and Takeda and participated in advisory boards (fees to institute) for Janssen, Bristol Myers Squibb, Sanofi, Oncopeptides, Amgen and Takeda. The other authors declare no competing interests.

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multiple myeloma, botkanker, ziekte van Kahler, Daratumumab, hyaluronidase-fihj, Darzalex Faspro, bortezomib, Velcade, lenalidomide, Revlimid, dexamethason, FDA, fase III studie CEPHEUS, ziektevrije ziekte, overall overleving


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