Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia.

BACKGROUND: Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65-year-old population. METHODS: A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated. RESULTS: Median age of our cohort was 76 (interquartile range, IQR, 70-81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8-21) days. Median time on response was 320 (IQR, 147-526) days. Sixty-three adverse events (AEs), mainly grade 1-2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self-limited pulmonary embolisms in secondary ITP were the only thrombotic events observed. CONCLUSION: Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD-ITP were poor. A relatively high number of deaths were observed.

Multiparameter Flow Cytometry Identification of Neoplastic Subclones: A New Biomarker in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.

Multiparameter flow cytometry (MFC)-based clonality assessment is a powerful method of diagnosis and follow-up in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). However, the relevance of intraclonal heterogeneity in immunophenotypic studies remains poorly understood. The main objective of this work was to characterize the different immunophenotypic subclones in MGUS and MM patients and to investigate their correlation with disease stages. An 8-color MFC protocol with 17 markers was used to identify the subclones within the neoplastic compartment of 56 MGUS subjects, 151 newly diagnosed MM patients, 30 MM subjects in complete remission with detectable minimal residual disease, and 36 relapsed/refractory MM patients. Two or more clusters were observed in > 85% of MGUS subjects, 75% of stage I MM patients, and < 15% in stage III. Likewise, a significant correlation between the dominant subclone size, secondary cytogenetic features, and changes in the expression of CD27, CD44, and CD81 was detected. The loss of intraclonal equilibrium may be an important factor related with kinetics and risk of progression not well considered to date in MFC studies. The MFC strategy used in this work can provide useful biomarkers in MGUS and MM.

Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice.

BACKGROUND: Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real-world setting. METHODS: A total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated. RESULTS: The median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45-75 yr). The median time with ITP diagnosis was 81 months (IQR, 30-192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2-4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty-six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 10(9) /L (IQR, 8-39 × 10(9) /L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9-13 d). Maintained platelet response rate during the 15-month period under examination was 75.2%. Twenty-eight patients (18.4%) experienced adverse events, mainly grades 1-2. CONCLUSION: Eltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP.

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.

Use of eltrombopag after romiplostim in primary immune thrombocytopenia.

The thrombopoietin receptor agonists (THPO-RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO-RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18-83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5-21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet-count fluctuation (n = 6) and side-effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow-up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet-count fluctuation and side-effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.