Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

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.

Life expectancy of follicular lymphoma patients in complete response at 30 months is similar to that of the Spanish general population.

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group.

The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.

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.

Sustained response after discontinuation of short-and medium-term treatment with eltrombopag in patients with immune thrombocytopenia.

Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy. However, when eltrombopag is discontinued, platelet counts usually return to baseline within 2 weeks. Here, we describe the clinical characteristics of the, to the best of our knowledge, largest case series of patients with ITP, who presented sustained responses after discontinuing eltrombopag (n = 12). The median time from diagnosis to eltrombopag initiation was 24 months (range, 1-480). The median number of prior therapies was 5 (range, 1-7), and the median duration of eltrombopag treatment was 5 months (range, 1-13). Three patients received eltrombopag for only 1 month. The treatment was well-tolerated. The median (range) follow-up of this case series was of 7 months (6-20), during which all patients maintained a safe platelet count without the need for anti-ITP treatment. The communication of such cases may support the conduction of new studies to investigate which predictive factors could identify ITP patients with sustained responses after discontinuing eltrombopag without additional therapy. The need of long-term use of eltrombopag should be re-examined.

Safety and efficacy of splenectomy in over 65-yrs-old patients with immune thrombocytopenia.

AIM: Few studies specifically focus on elderly splenectomized immune thrombocytopenia (ITP) patients. Older patients with ITP and excellent health are often excluded from surgery splenectomy. We aimed to compare the safety and efficacy of splenectomy in elderly and non-elderly ITP patients and to examine the effect of age on therapeutic response. MATERIAL AND METHODS: We carried out a retrospective analysis of a series of 218 patients who had undergone splenectomy for ITP. We compared the data from the elderly group (≥65 yrs, 57 patients) with the young group (<65 yrs, 162 patients). RESULTS: Surgical technique (laparoscopy or open laparotomy splenectomy) was comparable between the two age groups. The adjusted risk of major bleeding following splenectomy for elderly patients was three times that for young patients (OR 3.05, 95% CI: 1.44-6.52). The median duration of postoperative hospital stay was longer for elderly than for young patients (8 d vs. 4 d, P < 0.001). However, we identified a subgroup of elderly ITP patients, those aged between 65 and 70 yrs who had undergone laparoscopic splenectomy, with a low risk of postoperative complications. Of the 218 patients, 89% achieved a favorable response to splenectomy. A favorable response was significantly less common in elderly than in young people (79% vs. 92%, P = 0.005). However, we observed an acceptable long-term control of ITP in the elderly group, in which the probability of maintaining response for 14 yrs after splenectomy was 56%. CONCLUSIONS: Patients aged ≥65 yrs experienced negative effects on safety and efficacy outcomes of splenectomy for ITP, but further studies are needed to identify predictors of postsplenectomy outcomes in this group.

Pomalidomide, Cyclophosphamide, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma: Real-World Analysis of the Pethema-GEM Experience.

INTRODUCTION: Treatment of relapsed/refractory multiple myeloma (RRMM) is highly challenging, especially for patients with disease refractory to initial therapy, and in particular for disease developing refractoriness to lenalidomide. Indeed, with currently approved treatments, median progression-free survival (PFS) in the lenalidomide-refractory setting is less than 10 months, reflecting the difficulty in treating this patient population. Pomalidomide is a second-generation immunomodulatory drug that has shown activity in lenalidomide-refractory disease in the setting of different combinations. PATIENTS AND METHODS: A real-world study was conducted by the Spanish Myeloma group in a cohort of patients with RRMM treated with pomalidomide, cyclophosphamide, and dexamethasone (PomCiDex). One hundred patients were treated with a median of 3 prior lines of therapy. RESULTS: Overall response rate was 39%, with a clinical benefit rate of 93%. Median PFS was 7.6 months; median overall survival (OS) was 12.6 months. Median PFS and OS survival were consistent across the different subgroups analyzed. Prolonged PFS and OS were found in patients with responsive disease. CONCLUSION: Our results compared favorably with those obtained with different pomalidomide-based combinations in a similar patient population. PomCiDex remains a manageable, cost-effective, and all-oral triplet combination for RRMM patients.

Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens.

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

Efficacy and safety of eltrombopag in persistent and newly diagnosed ITP in clinical practice.

Eltrombopag is safe and effective in primary chronic ITP. However, lack of clinical trials avoids a clear demonstration of its utility in newly diagnosed and persistent ITP. Our aim here is to report Spanish results for this type of patients. We retrospectively evaluated 220 adult primary ITP patients. According to standard definition, patients were allocated to newly diagnosed (n = 30), persistent (n = 30), and chronic (n = 160) ITP. Groups were homogenous regarding most relevant parameters. 180 (90%) of 220 patients achieved a platelet response (R) with 167 (75.9%) complete responses (CR) after a 15-month follow-up. No statistical significant differences among groups but a trend towards a greater efficacy in newly diagnosed ITP were observed (93.3% of responses with 86.7% of CR). Efficacy in persistent ITP (83.3% of responses with 80.0% of CR) and chronic ITP (79.4% of responses with 73.1% of CR) was similar. 70 patients (31.8%) experienced adverse events. 15 of them were grade 3-4. Most common adverse effects were headache and hepatobiliary laboratory abnormalities (HBLAs). One persistent ITP had a venous thrombosis and one chronic ITP had grade II myelofibrosis. We consider Eltrombopag use for the early stage ITP as effective and safe as it is in chronic ITP.