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. 2021 Oct 13;16(10):e0258487.
doi: 10.1371/journal.pone.0258487. eCollection 2021.

The real-world outcomes of multiple myeloma patients treated with daratumumab

Agoston Gyula Szabo  1 , Tobias Wirenfeldt Klausen  2 , Mette Bøegh Levring  3 , Birgitte Preiss  4 , Carsten Helleberg  2 , Marie Fredslund Breinholt  5 , Emil Hermansen  6 , Lise Mette Rahbek Gjerdrum  7 , Søren Thorgaard Bønløkke  8 , Katrine Nielsen  8 , Eigil Kjeldsen  8 , Katrine Fladeland Iversen  1 , Elena Manuela Teodorescu  9 , Marveh Dokhi  10 , Eva Kurt  11 , Casper Strandholdt  12 , Mette Klarskov Andersen  13 , Annette Juul Vangsted  10
Affiliations

The real-world outcomes of multiple myeloma patients treated with daratumumab

Agoston Gyula Szabo et al. PLoS One. .

Abstract

Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019.

Methods: Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR).

Results: Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001).

Conclusion: The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Time to next treatment and overall survival of the first daratumumab therapy.
Patients at risk is shown below the figure. Abbreviations: Da-other = daratumumab in other combinations than IMiD and PI; mo = months.
Fig 2
Fig 2. Time to next treatment depending on the timing of daratumumab therapy.
Patients at risk is shown below each figure. A: TNT for all combinations of daratumumab depending on timing. Cox-regression analysis showed longer TNT in early lines (p<0.0001).
Fig 3
Fig 3. Time to next treatment of the first daratumumab therapy depending on cytogenetic abnormalities.
Patients at risk is shown below each figure. High-risk CA was defined as the presence of del17p, t(4:14) or t(14:16). Abbreviations: mo = months. A:TNT for for all combinations of daratumumab-containing line of therapy depending on CA. Compared with patients with standard-risk CA, patients with amp1q had similar TNT (p = 0.65). Patients with high-risk CA had a trend towards shorter TNT (p = 0.003).
See this image and copyright information in PMC

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