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Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer

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Abstract

Background

An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations.

Objective

To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer.

Patients and Methods

Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated.

Results

Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm3 (95% CI 110–177 cm3) to 209 cm3 (95% CI 161–257 cm3) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r2 = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655 μm2/s to 543 μm2/s, p = 0.11). No changes to portal vein diameter were seen.

Conclusions

Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.

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References

  1. Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68(22):9280–90.

  2. Lopus M, Oroudjev E, Wilson L, Wilhelm S, Widdison W, Chari R, et al. Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules. Mol Cancer Ther. 2010;9(10):2689–99.

  3. Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128(2):347–56.

    Article  CAS  PubMed  Google Scholar 

  4. Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol. 2010;28(16):2698–704.

  5. Burris H a., Rugo HS, Vukelja SJ, Vogel CL, Borson R a., Limentani S, et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2) -positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011;29(4):398–405.

  6. Krop IE, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, et al. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2012;30(26):3234–41.

  7. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.

  8. Gupta M, Wang B, Carrothers TJ, LoRusso PM, Chu YW, Shih T, et al. Effects of trastuzumab emtansine (T-DM1) on Qt interval and safety of pertuzumab plus T-DM1 in patients with previously treated human epidermal growth factor receptor 2-positive metastatic breast cancer. Clin Pharmacol Drug Dev. 2013;2(1):11–24.

    Article  CAS  PubMed  Google Scholar 

  9. Hurvitz SA, Dirix L, Kocsis J, Bianchi G V., Lu J, Vinholes J, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013;31(9):1157–63.

  10. Diéras V, Harbeck N, Budd GT, Greenson JK, Guardino AE, Samant M, et al. Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. J Clin Oncol. 2014;32(25):2750–7.

    Article  PubMed  Google Scholar 

  11. Force J, Saxena R, Schneider BP, Storniolo AM, Sledge GW, Chalasani N, et al. Nodular regenerative hyperplasia after treatment with trastuzumab emtansine. J Clin Oncol. 2016;34(3):e9–12.

  12. Poon KA, Flagella K, Beyer J, Tibbitts J, Kaur S, Saad O, et al. Preclinical safety pro fi le of trastuzumab emtansine ( T-DM1 ): Mechanism of action of its cytotoxic component retained with improved tolerability. Toxicol Appl Pharmacol. The Authors; 2013;273(2):298–313.

  13. Padhani AR. Diffusion magnetic resonance imaging in cancer patient management. Semin Radiat Oncol. 2011;21(2):119–40.

  14. Padhani AR, Makris A, Gall P, Collins DJ, Tunariu N, De Bono JS. Therapy monitoring of skeletal metastases with whole-body diffusion MRI. J Magn Reson Imaging. 2014;39(5):1049–78.

    Article  PubMed  Google Scholar 

  15. Woolf DK, Padhani a. R, Makris a. Assessing response to treatment of bone metastases from breast cancer: what should be the standard of care? Ann Oncol. 2015;26(6):1048–57.

  16. Padhani AR, Van Ree K, Collins DJ, D’Sa S, Makris A. Assessing the relation between bone marrow signal intensity and apparent diffusion coefficient in diffusion-weighted MRI. Am J Roentgenol. 2013;200(1):163–70.

    Article  Google Scholar 

  17. Mandal L, Mandal SK, Bandyopadhyay D, Datta S. Correlation of portal vein diameter and splenic size with gastro-oesophageal varices in cirrhosis of liver. J Indian Acad Clin Med. 2011;12(4):266–70.

    Google Scholar 

  18. Ciray I, Lindman H, Astrom G, Wanders A, Bergh J, Ahlstrom H. Effect of Granulocyte Colony-Stimulating Factor (G-CSF)-supported chemotherapy on MR imaging of normal red bone marrow in breast cancer patients with focal bone metastases. Acta Radiol. 2003;44:472–84.

    Article  CAS  PubMed  Google Scholar 

  19. Shen B-Q, Bumbaca D, Saad O, Yue Q, Pastuskovas C, Khojasteh SC, et al. Catabolic fate and pharmacokinetic characterization of T-DM1. Curr Drug Metab. 2012;13(7):901–10.

    Article  CAS  PubMed  Google Scholar 

  20. Padhani AR, Gogbashian A. Bony metastases: assessing response to therapy with whole-body diffusion MRI. Cancer Imaging. 2011;11:S1–S17.

    Article  Google Scholar 

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Authors and Affiliations

  1. Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK

    Michael Kosmin, Andreas Makris, David Woolf & David Miles

  2. Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK

    Noorulhuda Jawad & Anwar R. Padhani

Authors
  1. Michael Kosmin
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  2. Andreas Makris
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  3. Noorulhuda Jawad
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  4. David Woolf
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  5. David Miles
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  6. Anwar R. Padhani
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Corresponding author

Correspondence to Michael Kosmin.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

This article does not contain any studies with animals performed by any of the authors.

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The authors declare that they have no conflicts of interest.

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Kosmin, M., Makris, A., Jawad, N. et al. Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer. Targ Oncol 12, 229–234 (2017). https://doi.org/10.1007/s11523-017-0477-6

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  • DOI: https://doi.org/10.1007/s11523-017-0477-6

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