Blood. elderly males above the age of 70. Diagnosis of CLL requires the presence of lymphocytosis ( 5.0??109/L) of monoclonal B cells and characteristic immunophenotype in the peripheral blood or bone marrow. 1 , 2 , 3 Chemoimmunotherapy consisting of cytotoxic chemotherapy agents with anti\CD20 monoclonal antibody rituximab, Bruton tyrosine kinase (BTK) inhibitors like ibrutinib and BCL\2 inhibitors (venetoclax) are all considered first\line treatment options for patients with CLL depending on their clinical and genetic factors. 2 According to cancer statistics 2020, MM will account for 18% of hematological malignancies (32?270 cases of 178?520). 4 It is more common in males around the age of 65?years and in African Americans compared with Caucasians. According to current International Myeloma Working Group (IMWG) criteria, diagnosis of MM depends on the presence of, and number of clonal plasma cells in the bone marrow or a biopsy\proven plasmacytoma, immunoglobulin light chain restriction and ratio, skeletal lesions detected by MRI, and presence of end\organ damage (hypercalcemia, renal failure, anemia, and bone lesions), collectively known as SLiM CRAB criteria. 5 Management of MM includes immune modulators (like thalidomide, or lenalidomide), proteasome inhibitors like bortezomib and corticosteroids (dexamethasone). Newer drugs are used as single agents or with various combinations including carfilzomib, pomalidomide, daratumumab, ixazomib, elotuzumab, and selinexor. 6 The coexistence (+)-Alliin of both CLL and MM is very rare. 7 A study done between 2000 and 2015 at Mayo Clinic showed 28 of 10,735 (0.26%) patients diagnosed with MM to also have CLL. 1 As summarized in Table S1, 15 patients (53%) of those were diagnosed with CLL/SLL before MM; 11 patients (39%) were diagnosed simultaneously, and 2 patients developed CLL after MM diagnosis (8%). The clonal relationship between CLL and MM when they codevelop in the same patient is not clearly defined with some studies indicate two separate clones 8 , 9 while others support (+)-Alliin a common origin. 10 , 11 However, the ability of ibrutinib therapy to prevent development of MM in CLL patients is not known. Here, we report a patient with established diagnosis of CLL who developed MM while on maintenance therapy with Ibrutinib. 2.?CASE PRESENTATION A 55\years old Caucasian male with past medical history of Hashimoto’s disease, pernicious anemia, vitamin D deficiency, vitiligo, low testosterone, and cluster headaches presented to his primary care physician in 2013 for routine visit without new complaints. He was found to have mild elevation of white blood cell (WBC) count (14.1??103/L, upper limit of normal (ULN): 10.6??103/L). His WBC differential count showed normal neutrophil count of 3.1??103/L, elevated lymphocyte count of 10.2??103/L (ULN: 3.8??103/L), normal hemoglobin of 13.8?gm/dL, and normal platelets of CDKN1B 201 (103/L). Review of blood smear showed small lymphocytes with clumped chromatin characteristic of CLL. Physical examination revealed bilateral mid\cervical lymph nodes of 1\1.5?cm, a left supraclavicular lymph node (~1.5?cm), and a right axillary lymph node (~1\1.5?cm). There was no hepatosplenomegaly. Flow cytometry revealed monotypic B\cell population expressing dim kappa light chain, CD5, CD19, CD20, and CD23 consistent with CLL. Cells were negative for CD10 and FMC7. Cytogenetics by fluorescence in situ hybridization (FISH) showed 11q deletion in 77% of the nuclei and deletion of chromosome 13 in 43.5% of the nuclei. Additional work up at diagnosis included immunoelectrophoresis (IEP) that showed an IgA kappa monoclonal gammopathy of 75?mg/dL and a possible faint IgM heavy chain restriction. His serum\free Kappa light chain (FLC) was elevated at 3.15?mg/dL (normal: 0.33\1.94), lambda FLC was normal (0.96?mg/dL, normal range: 0.57\2.63?mg/dL). The patient was diagnosed with stage I CLL by Rai classification with two risk factors, a CD38? ?30%, and ZAP 70? ?30%. 12 The patient was under observation since he had no indication for CLL therapy until two and a half (+)-Alliin years later (2016) when he developed progressive fatigue and decreased blood counts (platelets 115??103/L, hemoglobin 11?gm/dL, and neutrophils 1.2??103/L). His total WBC also increased (26.2??103/L) as well as the size of his lymph nodes. A bone marrow aspiration and biopsy (Figure?1A) at that time showed (+)-Alliin increased cellularity estimated at 90%. Approximately 80%\90% of the (+)-Alliin cellularity was composed of a diffuse infiltrate of small lymphocytes (Figure?1B). The remaining cellular elements were adequate\appearing megakaryocytes, maturing erythroid and myelocytic cells; there was no increase in the number of plasma cells. FISH panel showed deletion of 11q.