Final Diagnosis -- Plasmacytoma with daratumumab interference presenting as a monoclonal IgG/kappa

FINAL DIAGNOSIS

Plasmacytoma with daratumumab interference presenting as a monoclonal IgG/kappa

DISCUSSION

This patient has a history of recurrent plasmacytoma. She has been closely followed up for disease recurrence and progression to MM. Upon identification of a new bone lesion at distal femur, which was not amenable to radiation therapy due to its close proximity to the knee joint, daratumumab was started as a single systemic therapeutic agent. A month later, a characteristic IgG/kappa band appeared on both SPE and IFE, most consistent with the presence of daratumumab instead of the development of a new clone. This should not be mistaken as the evidence of progression to IgG/kappa MM.

Daratumumab in patients' serum has been misidentified as the persistence of endogenous mAb or the development of a new clone. As the application of daratumumab and other therapeutic mAbs is growing, improving the awareness among clinicians and clinical laboratories that therapeutic mAbs can positively interfere with both SPE and IFE is imperative to prevent misdiagnosis. However, at present, there is no commercially available test to confirm the presence of daratumumab in patient samples. Therefore, the possibility that an endogenous serum IgG/kappa co-migrates with darartumumab cannot be theoretically excluded.

REFERENCES

  1. McKenna RW, Kyle RA, Kuehl WM, et al. Plasma cell neoplasms. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2008:200-213.
  2. Nolan KD, Mone MC, Nelson EW. Plasma cell neoplasms: Review of disease progression and report of a new variant. Surg Oncol, 2005, 14(2):85-90.
  3. Munshi NC, Tricot G, Barlogie B. Plasma cell neoplasms. V.T. DeVita, S. Hellman, S.A. Rosenberg (Eds.), Cancer: principles and practice of oncology, Lippincott Williams & Wilkins, Philadelphia 2001, 2465-2499.
  4. Dispenzieri A, Lacy MQ, Greipp PR. Multiple myeloma J.P. Greer, G.M. Rodgers, J. Foerster, F. Paraskevas, J.N. Lukens, B. Galder (Eds.), Wintrobe's clinical hematology, Lippincott Williams & Wilkins, Philadelphia 2004, 2582-2636.
  5. Wilder RB, Ha CS, Cox JD, Weber D, Delasalle K, Alexanian R. Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of bone. Cancer. 2002;94:1532-1537.
  6. Galieni P, Cavo M. Pulsoni A. et al. Clinical outcome of extramedullary plasmacytoma. Haematologica, 2000;85:47-51.
  7. Dispenzieri A, Lacy MQ, Greipp PR. Multiple myeloma. J.P. Greer, G.M. Rodgers, J. Foerster, F. Paraskevas, J.N. Lukens, B. Galder (Eds.), Wintrobe's clinical hematology, Lippincott Williams & Wilkins, Philadelphia 2004, 2582-2636.
  8. Rajkumar SV, Kyle RA, Buadi FK. Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence. Mayo Clin Proc. 2010;85(10):945.
  9. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412.
  10. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22):5418.
  11. Durie BG, Kyle RA, Belch A, et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J. 2003;4:379-398.
  12. Moreau P, Attal M, Facon T. Frontline therapy of multiple myeloma. Blood. 2015;125:3076-84.
  13. Plesner T, Arkenau HT, Gimsing P. et al. Daratumumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma: Updated Results of a Phase 1/2 Study (GEN503). Blood. 2015;126:507
  14. FDA. Darzalex. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf (Accessed November 2017).
  15. Mills JR, Murray DL. Identification of Friend or Foe: The Laboratory Challenge of Differentiating M-Proteins from Monoclonal Antibody Therapies. JALM: An AACC publication. 2017;1(4):421-431.

Contributed by Li Liu, MD, PhD



Case IndexCME Case StudiesFeedbackHome