Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Oct;1(10):e41.
doi: 10.1038/bcj.2011.42. Epub 2011 Oct 28.

The therapeutic human CD38 antibody daratumumab improves the anti-myeloma effect of newly emerging multi-drug therapies

M S van der Veer, M de Weers, B van Kessel, J M Bakker, S Wittebol, P W H I Parren, H M Lokhorst, T Mutis

The therapeutic human CD38 antibody daratumumab improves the anti-myeloma effect of newly emerging multi-drug therapies

M S van der Veer et al. Blood Cancer J. 2011 Oct.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Addition of DARA to BORT-LEN significantly increases the MM cell lysis in BM-MNC of MM patients, particularly in LEN/BORT low responder or refractory patients. (a) BM-MNC from MM patients (n=16), containing 2–20% CD138+ MM cells as detected by flow cytometry were incubated with LEN (3 μ), BORT (3 n) and DARA (10 μg/ml) alone or in combination for 48 h in RPMI+ 10% fetal bovine serum in 96-well u bottom plates in fully humidified incubators at 37 °C, 5% CO2-air mixture. Surviving MM cells were enumerated by the single-platform fluorescence-activated cell sorting analysis of CD138+ cells in the presence of Tru-Count beads (Beckman Coulter, Miami, FL, USA). Percentage lysis of MM cells in LEN, DARA and LEN+DARA-treated conditions were calculated using the MM survival of wells treated with the control KLH antibody alone. Differences between indicated groups were tested for significance in repeated measures analysis of variance (ANOVA), using Bonferonni's post-hoc multiple comparison tests with two-tailed 95% confidence intervals. In b–d, data are analyzed for low LEN/BORT responders, high LEN/BORT responders and LEN/BORT refractory patients, respectively. aP-values were calculated using a repeated measures ANOVA. bP-values were calculated by a paired t-test. cExpected values were calculated to test the null hypothesis that there is no synergism between DARA and LEN/BORT using the following formula: % expected lysis=100−%survival after DARA × %survival after LEN/BORT.
Figure 2
Figure 2
DARA increases response against MM in triple chemotherapy treatments. BM-MNC form patients (n=7) were incubated with increasing dilutions of a cocktail of (a) LEN, BORT and DEX (1 × dilution contains: 1 μ LEN, 1 n BORT and 1 μ DEX) or with a cocktail of (b) MEL, PRED, BORT (1 × dilution contains 1 μ MEL, 1 μ PRED and 1 n BORT) in the presence or absence of DARA (10 μg/ml) for 48 h. Surviving MM cells were enumerated by fluorescence-activated cell sorting analysis of CD138+ cells. P-values were calculated by a paired t-test. *P<0.05, ***P<0.001.
See this image and copyright information in PMC

References

    1. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood. 2008;111:2521–2526. - PubMed
    1. Cavo M, Rajkumar SV, Palumbo A, Moreau P, Orlowski R, Blade J, et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011;117:6063–6073. - PMC - PubMed
    1. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007;25:3892–3901. - PubMed
    1. Hallek M, Pflug N. State of the art treatment of chronic lymphocytic leukaemia. Blood Rev. 2011;25:1–9. - PubMed
    1. Ahmadi T, Chong EA, Gordon A, Leinbach L, Aqui NA, Nasda SD, et al. Phase II trial of lenalidomide—dexamethasone—rituximab in relapsed or refractory indolent B-cell or mantle cell lymphomas resistant to rituximab. Blood (ASH Annual Meeting Abstracts) 2010;116:3962.