Second Myeloid and Lymphoid Malignancies in patients with Chronic Lymphocytic Leukemia

Autor: Gabriela Corrales, Jennifer Rock-Klotz, Jose Sandoval, Julio C. Chavez, Javier Pinilla-Ibarz
Rok vydání: 2015
Předmět:
Zdroj: Clinical Lymphoma Myeloma and Leukemia. 15:S207-S208
ISSN: 2152-2650
DOI: 10.1016/j.clml.2015.04.070
Popis: in relapsed/refractory (R/R) CLL. Ofatumumab, an anti-CD20 antibody, has activity in combination with chemotherapy in CLL. Objective: Evaluate safety and activity of ibrutinib combined with ofatumumab (phase Ib/II) in 3 different sequences. Patients: Patients with R/R CLL/SLL, PLL, or Richter’s transformation (RT) after 2 prior therapies, including a purine analogue. Intervention: 420 mg oral ibrutinib daily and IV ofatumumab 300/2000 mg (12 doses). Group (G) 1: 1 cycle of ibrutinib, then ofatumumab added; G2: ofatumumab on day (D) 1/cycle (C) 1 and ibrutinib on D2/C1; G3: 2 cycles of ofatumumab, then ibrutinib added on D1/ C3. Results: 71 patients (27, 20, 24 in G1, G2, G3) enrolled; median age 64 years; Rai stage III/IV 61%; 65 had CLL, 1 SLL, 2 PLL, and 3 RT; bulky disease ( 5 cm) in 75%; del(17p) in 44%; del(11q) in 31%. Most frequent AEs included diarrhea (68%), infusion-related reaction (IRR, 45%), peripheral sensory neuropathy (42%), and stomatitis (37%). AEs grade 3 occurred in 61%; most common grade 3-4 AE was neutropenia (17%). Serious AEs occurred in 39%, including grade 3 IRR in 1 patient (G2). AEs led to ibrutinib discontinuation in 6 patients. Nine patients died within 30 days of last dose and 2 within follow-up. ORR in CLL/SLL was 100% in G1, 79% in G2, and 71% in G3. One patient had complete response; 2 additional patients achieved partial response with lymphocytosis. Four patients in G3 progressed before starting ibrutinib. At study end, 52/58 responders (90%) remained progression-free with follow-up of 16, 12, and 11 months for G1, G2, and G3, respectively. The three RT patients had disease control followed by progression on days 471, 168, and 137. At 12 months, PFS was 89%, 85%, and 75% in G1, G2, and G3, respectively; 76% continued ibrutinib in long-term extension study; 2 patients underwent transplant. Conclusions: Ibrutinib combined with ofatumumab is well tolerated and highly active in R/R CLL/SLL with all 3 dosing sequences. Based on these compelling results, randomized trials evaluating anti-CD20 antibody in combination with ibrutinib are ongoing. 310 Second Myeloid and Lymphoid Malignancies in patients with Chronic Lymphocytic Leukemia Jose Sandoval, Gabriela Corrales, Jennifer Rock-Klotz, Javier Pinilla-Ibarz, Julio Chavez Malignant Hematology, H. Lee Moffitt Cancer Center, University of South Florida; Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute Introduction: Chronic lymphocytic Leukemia (CLL) as the most common chronic leukemia is associated with increased second malignancies. We describe the characteristics of CLL patients who develop second myeloid (SMD) or lymphoid disorders (SLD). Methods: This is a retrospective review of CLL patients with of SLD and SMD from 01/2000 to 12/2012 using the Moffitt Cancer Canter and Total Cancer Care databases. The primary objective was to identify risk factors for SLD and SMD development. CLL patients with no malignancies were the control. Overall survival (OS) was estimated and compared by the Kaplan-Meier method and the long-rank test. Results: We identified 211 CLL patients with second malignancies in a cohort of 844. Sixty-nine patients had SLD (47) and SMD (22). SLD diagnosis included: DLBCL1⁄4 40, MM1⁄44, PLL1⁄4 1, HCL1⁄41, CTCL1⁄41. SMD diagnosis included MDS1⁄4 15, AML/MDS1⁄47. The OS for patients with SLD, SMD and control were 11.4, 8.1 (p1⁄4 0.063) and 10.7 years (p1⁄4 0.261), respectively. The median OS from SLD and SMD diagnosis were 1.2 and 1.3 years, respectively. Table 1 shows Chi-square analysis. Conclusions: Advanced Rai stage and unmutated IgVH status were associated with increased risk of SLD while no factors were found for SMD. Secondary hematological malignancies in CLL patients show a short median OS. Clinical Lymphoma, Myeloma & Leukemia June 2015 S207 Table 1 Chi-Square Analysis No second malignancies SLD p-Value SMD p-Value Gender M 400 (63%) 33 (70%) 0.43 15 (68%) 0.82 F 233 (37%) 14 (30%) 7 (32%) Age >60 304 (48%) 24 (51%) 0.76 13 (59%) 0.66
Databáze: OpenAIRE
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