Evans syndrome: Disease awareness and clinical management in a nation-wide ITP-NET survey.

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization.

Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia.

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.

Refractory primary immune thrombocytopenia (ITP): current clinical challenges and therapeutic perspectives.

Chronic primary immune thrombocytopenia (ITP) can today benefit from multiple therapeutic approaches with proven clinical efficacy, including rituximab, thrombopoietin receptor agonists (TPO-RA), and splenectomy. However, some ITP patients are unresponsive to multiple lines of therapy with prolonged and severe thrombocytopenia. The diagnosis of refractory ITP is mainly performed by exclusion of other disorders and is based on the clinician's expertise. However, it significantly increases the risk of drug-related toxicity and of bleedings, including life-threatening events. The management of refractory ITP remains a major clinical challenge. Here, we provide an overview of the currently available treatment options, and we discuss the emerging rationale of new therapeutic approaches and their strategic combination. Particularly, combination strategies may target multiple pathogenetic mechanisms and trigger additive or synergistic effects. A series of best practices arising both from published studies and from real-life clinical experience is also included, aiming to optimize the management of refractory ITP.

Anti-CD38 monoclonal antibodies in multiple myeloma with gain/amplification of chromosome arm 1q: a review of the literature.

INTRODUCTION: Gain/amplification of 1q (+1q) represents one of the most prevalent cytogenetic abnormalities (CAs) observed in multiple myeloma (MM). Historical studies predating the advent of anti-CD38 monoclonal antibodies (moAbs) implicated + 1q in poor prognoses, prompting its integration into novel staging systems. However, with the emergence of daratumumab and isatuximab, two pivotal anti-CD38 moAbs, the landscape of MM therapy has undergone a profound transformation. AREAS COVERED: This review encompasses a comprehensive analysis of diverse study methodologies, including observational investigations, clinical trials, meta-analyses, and real-world database analyses. By synthesizing these data sources, we aim to provide an overview of the current understanding of + 1q in the context of anti-CD38 moAbs therapies. EXPERT OPINION: Despite the paucity of available data, evidence suggests a potential mitigating effect of daratumumab on the adverse prognostic implications of + 1q. However, this benefit seems to diminish in patients harboring ≥ 4 copies or with concurrent high-risk CAs. On the other hand, isatuximab demonstrated promising outcomes in the relapsed-refractory setting for + 1q MM patients. Nevertheless, direct comparison between the two compounds is currently challenging. The current evidence firmly supports the integration of anti-CD38 moAb-based therapies as the standard of care for + 1q patients, pending further elucidation.

Prednisone vs high-dose dexamethasone in newly diagnosed adult primary immune thrombocytopenia: a randomized trial.

ABSTRACT: A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410.

Subcutaneous bortezomib-containing regimens as up-front treatment of newly diagnosed transplant-eligible multiple myeloma patients: a retrospective, non-interventional observational study.

Subcutaneous (SC) bortezomib-based regimens represent the standard induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma patients. Published data are based principally on intravenous (IV) administration: this retrospective observational study aimed to define patients' outcomes upon SC bortezomib administration, before and after ASCT. Of 131 enrolled patients, 86% received bortezomib-dexamethasone plus thalidomide (VTD), 5% plus cyclophosphamide (VCD), and 9% alone (VD), for a median of 4 cycles induction therapy, followed by single (52%) or double (48%) ASCT. 48 patients received consolidation with the same induction regimen. 35% had at least one adverse event, mainly gastrointestinal disorders and peripheral neuropathy (PN). ORR was 93.1%, 97.7% and 100%, after induction, ASCT(s) and consolidation, respectively. Median PFS and PFS2 were 55.8 months and 72 months, respectively, (median follow-up 45.3 months), while median OS was unreached. Concluding, SC bortezomib has similar efficacy with reduced PN than IV administration.

Management of elderly patients with immune thrombocytopenia: Real-world evidence from 451 patients older than 60 years.

INTRODUCTION: Primary Immune thrombocytopenia (ITP) in the elderly is a major clinical challenge which is increasingly frequent due to global ageing population. MATERIALS AND METHODS: To describe baseline ITP features, management, and outcome, a centralized electronic database was established, including data of 451 patients aged ≥60 years that were treated from 2000 onwards and were observed for ≥1 year (total observation of 2704 patient-years). RESULTS: At ITP diagnosis, median age was 71.1 years (age ≥ 75: 42.8%); 237 (53.9%) patients presented with haemorrhages (grade ≥ 3: 7.5%). First-line therapy included prednisone (82.9%), dexamethasone (14.6%), thrombopoietin-receptor agonists (TRAs, 1.3%), and oral immunosuppressive agents (1.1%). Prednisone starting dose ≥1 mg/kg/d (p = .01) and dexamethasone 40 mg/d (p < .001) were mainly reserved to patients aged 60-74, who were more treated with rituximab (RTX, p = .02) and splenectomy (p = .03) second-line. Overall response rates to first and second-line therapies were 83.8% and 84.5%, respectively, regardless of age and treatment type/dose. A total of 178 haemorrhages in 101 patients (grade ≥ 3: n. 52, 29.2%; intracranial in 6 patients), 49 thromboses in 43 patients (grade ≥ 3: n. 26, 53.1%) and 115 infections in 94 patients (grade ≥ 3: n. 23, 20%) were observed during follow-up. Incidence rates of complications per 100 patient-years were: 4.5 (haemorrhages, grade ≥ 3: 1.7), 1.7 (thromboses, grade ≥ 3: 0.9), and 3.9 (infections, grade ≥ 3: 0.7). TRAs use were associated with reduced risk of bleeding and infections, while cardiovascular risk factors (particularly, diabetes) significantly predicted thromboses and infections. CONCLUSIONS: Age-adapted treatment strategies are required in elderly and very elderly patients.

Bendamustine, Low-dose dexamethasone, and lenalidomide (BdL) for the treatment of patients with relapsed/refractory multiple myeloma confirms very promising results in a phase I/II study.

Lenalidomide and dexamethasone are an effective treatment for naïve and relapsed multiple myeloma (MM) patients. Bendamustine is a good option for B-cell malignancies showing only partial cross resistance with alkylating agents used in MM patients. Based on these considerations, we proposed a phase I/II study testing escalating doses of bendamustine and lenalidomide and fixed low doses of dexamethasone (BdL). Fifteen patients were enrolled in phase I study. Maximum tolerated dose was established at dose "level 0": bendamustine 40 mg/m2 days 1,2; lenalidomide 10 mg days 1-21; d 40 mg days 1,8,15,22 every 28-day cycle, for six cycles. We enrolled 23 patients in the phase II study. BdL combination showed mainly hematological toxicities, fever and infections. Overall response rate was 47%. After median follow up of 22 months, median PFS was 10 months. Two-years OS rate was 65%. BdL combination confirmed to be a promising treatment for patients with relapsed/refractory MM.