An Overview of Light Chain Multiple Myeloma: Clinical Characteristics and Rarities, Management Strategies, and Disease Monitoring

Abdul Rafae, Mustafa N Malik, Muhammad Abu Zar, Seren Durer, Ceren Durer, Abdul Rafae, Mustafa N Malik, Muhammad Abu Zar, Seren Durer, Ceren Durer

Abstract

Light chain multiple myeloma (LCMM) constitutes approximately 15% of patients with multiple myeloma (MM). It has a poorer prognosis when compared to immunoglobulin (Ig) G or IgA variant. We performed a comprehensive literature search on LCMM and identified a total of 390 articles. After a detailed screening, six studies involving a total of 1054 LCMM patients were included. A literature review revealed bone pain and renal failure as the most common initial sign and symptoms while extramedullary disease (EMD) was acquired later during the progression of the disease. Bortezomib has shown superior efficacy in LCMM patients over nonbortezomib regimens as demonstrated by better overall response rate (95.5% vs. 60%), progression-free survival (PFS) (25% vs. 9% at two years), and overall survival (OS) (24% vs. 9% at five years). Moreover, better PFS was seen, when bortezomib was used in combination with bendamustine compared to dexamethasone (95% vs. 25% at two years). Similarly, better OS (90% at two years) was observed with bortezomib in combination with bendamustine. Monitoring of disease should include serum free light chain levels, as literature review revealed that serum assays were more sensitive in indicating the disease and predicting PFS and OS as compared to urine assays. We provide presentation patterns, clinical rarities, management strategies including their efficacy, and disease monitoring in patients with LCMM in our review paper.

Keywords: bortezomib; light chain only multiple myeloma; survival.

Conflict of interest statement

The authors have declared that no competing interests exist.

References

    1. Multiple myeloma: 2014 Update on diagnosis, risk‐stratification, and management. Rajkumar SV. Am J Hematol. 2014;89:998–1009.
    1. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. Lancet Oncol. 2014;15:538–548.
    1. Serum N-glycans: a new diagnostic biomarker for light chain multiple myeloma. Chen J, Fang M, Zhao YP, et al. PLoS One. 2015;10:127022.
    1. Cancer statistics, 2014. Siegel R, Ma J, Zou Z, et al. CA Cancer J Clin. 2014;64:9–29.
    1. Cancer statistics, 2016. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2016;66:7–30.
    1. Incidence of multiple myeloma in Olmsted County, Minnesota. Kyle RA, Therneau TM, Rajkumar SV, et al. Cancer. 2004;101:2667–2674.
    1. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Rajkumar SV. Am J Hematol. 2016;91:719–734.
    1. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Landgren O, Weiss B. Leukemia. 2009;23:1691.
    1. Myelomatous involvement of the central nervous system. Paludo J, Painuly U, Kumar S, et al. Clin Lymphoma Myeloma Leuk. 2016;16:644–654.
    1. Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma. Short KD, Rajkumar SV, Larson D, et al. Leukemia. 2011;25:906.
    1. Subglottic extramedullary plasmacytoma with light chain multiple myeloma masquerading as adult-onset asthma. Gan YJ, Chopra A, Kanagalingam J. J Voice. 2014;28:394–391.
    1. Central nervous system infiltration by plasma cells: rare occurrence in multiple myeloma patients. Jorge A, Coelho I, Afonso C, et al. Clin Lymphoma Myeloma Leuk. 2015;15:125–126.
    1. Central nervous system involvement with multiple myeloma: long term survival can be achieved with radiation, intrathecal chemotherapy, and immunomodulatory agents. Chen CI, Masih‐Khan E, Jiang H, et al. Br J Haematol. 2013;162:483–488.
    1. Dual light chain extramedullary myeloma presenting with mediastinal lymphadenopathy and lytic bone lesions. Vlachostergios PJ, Oikonomou KG, Hussain A, et al. Hematol Oncol Stem Cell Ther. 2016;9:162–164.
    1. Review of 1027 patients with newly diagnosed multiple myeloma. Kyle RA, Gertz MA, Witzig TE, et al. Mayo Clin Proc. 2003;78:21–33.
    1. Comparison of modern and conventional imaging techniques in establishing multiple myeloma‐related bone disease: a systematic review. Regelink JC, Minnema MC, Terpos E, et al. Br J Haematol. 2013;162:50–61.
    1. Light chain multiple myeloma, clinic features, responses to therapy and survival in a long-term study. Zhang JJ, Sun WJ, Huang ZX, et al. World J Surg Oncol. 2014;12:234.
    1. Multiple myeloma. Kyle RA, Rajkumar SV. N Engl J Med. 2004;351:1860–1873.
    1. Monitoring of light chain myeloma - time for a change. Mollee P, Tate J. Br J Haematol. 2017;178:177–178.
    1. Light-chain only multiple myeloma is due to the absence of functional (productive) rearrangement of the IgH gene at the DNA level. Magrangeas F, Cormier ML, Descamps G, et al. Blood. 2004;103:3869–3875.
    1. Successful treatment of patients with newly diagnosed/untreated light chain multiple myeloma with a combination of bendamustine; prednisone and bortezomib (BPV) Mrachacz H, Khoder N, Plötze M, et al. Clin Lymphoma Myeloma Leuk. 2015;15:167–168.
    1. Successful treatment of patients with newly diagnosed/untreated light chain multiple myeloma with a combination of bendamustine, prednisone and bortezomib (BPV) Tessenow H, Holzvogt M, Holzvogt B, et al. J Cancer Res Clin Oncol. 2017;143:2049–2058.
    1. Diagnosis and monitoring for light chain only and oligosecretory myeloma using serum free light chain tests. Heaney JLJ, Campbell JP, Griffin AE, et al. Br J Haematol. 2017;178:220–230.
    1. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma. Dejoie T, Corre J, Caillon H, et al. Blood. 2016;128:2941–2948.
    1. Serum test for assessment of patients with Bence Jones myeloma. Bradwell AR, Carr-Smith HD, Mead GP, et al. Lancet. 2003;361:489–491.
    1. Bence Jones myeloma with signet-ring-like plasma cells. Caenazzo A, Sartori D, Poletti A. . Haematologica. 1997;82:122.
    1. Signet ring-like light chain myeloma with systemic spread. Haidar JH, Bazarbachi A, Nasr MR, et al. Eur J Haematol. 2003;70:249–250.
    1. Auer rod-like inclusions in kappa light chain myeloma. Noujaim JC, D'Angelo G. Blood. 2013;122:2932.
    1. Updated diagnostic criteria and staging system for multiple myeloma. Rajkumar SV. Am Soc Clin Oncol Educ Book. 2016;35:418–423.
    1. Optimizing treatment strategies in myeloma cast nephropathy: rationale for a randomized prospective trial. Bridoux F, Fermand J-P. Adv Chronic Kidney Dis. 2012;19:333–341.
    1. Clinicopathologic correlations in multiple myeloma: a case series of 190 patients with kidney biopsies. Nasr SH, Valeri AM, Sethi S, et al. Am J Kidney Dis. 2012;59:786–794.
    1. Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cut-off hemodialysis. Hutchison CA, Bradwell AR, Cook M, et al. . Clin J Am Soc Nephrol. 2009;4:745–754.
    1. Combined proximal tubulopathy, crystal-storing histiocytosis, and cast nephropathy in a patient with light chain multiple myeloma. Wu CK, Yang AH, Lai HC, et al. BMC Nephrol. 2017;18:170.
    1. Acquired Fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma. Ma CX, Lacy MQ, Rompala JF, et al. Blood. 2004;104:40–42.
    1. Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome. El Hamel C, Thierry A, Trouillas P, et al. Nephrol Dial Transplant. 2010;25:2982–2990.
    1. Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients. Messiaen T, Deret S, Mougenot B, et al. Medicine. 2000;79:135–154.
    1. Light chain proximal tubulopathy: clinical and pathologic characteristics in the modern treatment era. Stokes MB, Valeri AM, Herlitz L, et al. J Am Soc Nephrol. 2016;27:1555–1565.
    1. Light chain multiple myeloma with cutaneous AL amyloidosis. Becker MR, Rompel R, Plum J, et al. J Dtsch Dermatol Ges. 2008;6:744–745.
    1. The spectrum of cutaneous disease in multiple myeloma. Bayer-Garner IB, Smoller BR. J Am Acad Dermatol. 2003;48:497–507.
    1. Lambda light chain myeloma presenting as nodular hepatic lesion: a clinical rarity. Pal S, Chattopadhyay B, Chatterjee A, et al. J Cancer Res Ther. 2014;10:191–193.
    1. Spinal cord compression revealing a lambda light chain multiple myeloma. Durel CA, Vigne C, Muis-Pistor O, et al. Joint Bone Spine. 2013;80:538.
    1. Subglottic plasmacytoma: a case report and review of the literature. Wein RO, Topf P, Sham RL. Am J Otolaryngol. 2002;23:112–118.
    1. Cutaneous involvement in multiple myeloma: a clinicopathologic, immunohistochemical, and cytogenetic study of 8 cases. Requena L, Kutzner H, Palmedo G, et al. Arch Dermatol. 2003;139:475–486.
    1. Kappa light chain myeloma with initial cutaneous involvement. Saka B, Erten N, Ozturk G, et al. Ann Hematol. 2006;85:272–274.
    1. Progression from light chain myeloma to secondary plasma cell leukemia accompanied by peripheral blood eosinophilia. Robier C, Egger M, Wiesinger K, et al. Clin Chem Lab Med. 2015;53:305–307.
    1. Significantly better prognosis for patients with primary plasma cell leukemia than for patients with secondary plasma cell leukemia. Cha CH, Park CJ, Huh JR, et al. Acta Haematol. 2007;118:178–182.
    1. Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis. Powe DG, Kormelink TG, Sisson M, et al. J Allergy Clin Immunol. 2010;125:139–145.
    1. Bendamustine for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. Dennie TW, Kolesar JM. Clin Ther. 2009;31:2290–2311.
    1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Rajkumar SV, Harousseau J-L, Durie B, et al. Blood. 2011;117:4691–4695.

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