Introduction. Lymphoplasmacytic lymphoma (LPL) is characterised by the proliferation of B lymphocytes with varying degrees of plasmacytic differentiation involving bone marrow (BM), lymph nodes or spleen. Waldenstrom macroglobulinemia (WM) is a subset of LPL in which the malignant clone produces IgM paraprotein. LPL patients with IgA/IgG paraprotein account for less than 5% of LPLs. MYD88 mutation triggers survival through BTK activation in WM, a disease responding to ibrutinib, whereas nonIgM LPL has not been extensively investigated at the molecular level. Case report. In 2014 a 66 yearold woman presented with symptomatic anaemia (Haemoglobin, Hb: 9 g/dl), with IgAk monoclonal spike (1.6 g/dl) (Figure 1) and an otherwise unremarkable serum chemistry profile. A BM biopsy showed an 80% infiltrate by lymphocytes and lymphoplasmacytoid cells. A computed tomography (CT) scan documented neither adenopathy nor splenomegaly. Diagnosis of IgAsecreting LPL was made. The patient was treated with rituximabcyclophosphamidedexamethasone (RCD) with minor response (Figure 1). Eighteen months later she presented with progressive disease (Hb 8 g/dl, IgAk monoclonal spike 1.9 g/dl). After 5 cycles of bendamustine, the BM aspirate showed 90% lymphoid cells. Adenopathies, splenomegaly and ascites were noted on a CT scan. After 3 cycles of cyclophosphamidedoxorubicinvincristineprednisone (CHOP) our patient developed thrombocytopenia (Platelets, PLT: 30x10^9/L), transfusiondependent anaemia (Hb 7.7 g/dl) and clinical deterioration (Figure 1). We performed genetic studies of peripheral blood lymphocytes with a targeted NGS approach detecting mutations in 20 genes frequently mutated in CLL (ATM, BIRC3, BRAF, CDKN2A, PTEN, CDH2, DDX3X, FBXW7, KIT, KLHL6, KRAS, MYD88, NOTCH1, NRAS, PIK3CA, POT1, SF3B1, TP53, XPO1, ZMYM3). Given the identification of MYD88 L265P mutation in the peripheral blood, ibrutinib appeared a reasonable option. In February 2018 our patient started ibrutinib 420 mg/die (Figure 1). Hb and PLT improved from day +35 (Hb 1012 g/dl, PLT > 100x10^9/L). In July 2018 no ascites and 50% reduction of adenopathies and spleen were shown on a CT scan. In April 2019 the patient was still on full dose ibrutinib with transfusion independence and good performance status. Conclusion. To the best of our knowledge this is the first case of response to ibrutinib in a refractory IgA LPL with MYD88 mutation.
Response to ibrutinib of a refractory IgA lymphoplasmacytic lymphoma carrying the MYD88 L265P gene mutation.
Quaglia FM;
2019-01-01
Abstract
Introduction. Lymphoplasmacytic lymphoma (LPL) is characterised by the proliferation of B lymphocytes with varying degrees of plasmacytic differentiation involving bone marrow (BM), lymph nodes or spleen. Waldenstrom macroglobulinemia (WM) is a subset of LPL in which the malignant clone produces IgM paraprotein. LPL patients with IgA/IgG paraprotein account for less than 5% of LPLs. MYD88 mutation triggers survival through BTK activation in WM, a disease responding to ibrutinib, whereas nonIgM LPL has not been extensively investigated at the molecular level. Case report. In 2014 a 66 yearold woman presented with symptomatic anaemia (Haemoglobin, Hb: 9 g/dl), with IgAk monoclonal spike (1.6 g/dl) (Figure 1) and an otherwise unremarkable serum chemistry profile. A BM biopsy showed an 80% infiltrate by lymphocytes and lymphoplasmacytoid cells. A computed tomography (CT) scan documented neither adenopathy nor splenomegaly. Diagnosis of IgAsecreting LPL was made. The patient was treated with rituximabcyclophosphamidedexamethasone (RCD) with minor response (Figure 1). Eighteen months later she presented with progressive disease (Hb 8 g/dl, IgAk monoclonal spike 1.9 g/dl). After 5 cycles of bendamustine, the BM aspirate showed 90% lymphoid cells. Adenopathies, splenomegaly and ascites were noted on a CT scan. After 3 cycles of cyclophosphamidedoxorubicinvincristineprednisone (CHOP) our patient developed thrombocytopenia (Platelets, PLT: 30x10^9/L), transfusiondependent anaemia (Hb 7.7 g/dl) and clinical deterioration (Figure 1). We performed genetic studies of peripheral blood lymphocytes with a targeted NGS approach detecting mutations in 20 genes frequently mutated in CLL (ATM, BIRC3, BRAF, CDKN2A, PTEN, CDH2, DDX3X, FBXW7, KIT, KLHL6, KRAS, MYD88, NOTCH1, NRAS, PIK3CA, POT1, SF3B1, TP53, XPO1, ZMYM3). Given the identification of MYD88 L265P mutation in the peripheral blood, ibrutinib appeared a reasonable option. In February 2018 our patient started ibrutinib 420 mg/die (Figure 1). Hb and PLT improved from day +35 (Hb 1012 g/dl, PLT > 100x10^9/L). In July 2018 no ascites and 50% reduction of adenopathies and spleen were shown on a CT scan. In April 2019 the patient was still on full dose ibrutinib with transfusion independence and good performance status. Conclusion. To the best of our knowledge this is the first case of response to ibrutinib in a refractory IgA LPL with MYD88 mutation.
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