Response Assessment to Erythropoietin-Zeta (Epo-Alpha Biosimilar) Therapy in Low-Risk Myelodysplastic Syndromes.

BACKGROUND: This prospective observational study aimed to verify the efficacy of erythropoietin zeta in the treatment of patients with low-risk myelodysplastic syndrome. METHODS: Patients with low/int-1 IPSS risk and serum erythropoietin level below 500 U/L were enrolled. Treatment consisted of erythropoietin zeta 40,000 U subcutaneously once a week. The primary endpoint was the erythroid response. According to Simon's two-stage statistical design, 36 patients were recruited. The median age was 75 years (range 56-83 years), male/female ratio was 1.1/1, median baseline serum erythropoietin was 57.9 U/L (range 9.4-475 U/L). 53% of patients had low-risk disease, while the remaining had Int-1 risk. RESULTS: After 8 weeks, a significant response (rise in Hb levels of at least 1.5 g/dL) was achieved in 18 patients (50%) out of 36. However, 17 patients did not improve; 8/17 patients pursued the 40,000 U weekly schedule of erythropoietin zeta, and 4/8 (50%) of them reached the erythroid response after 16 weeks. Nine patients underwent dosage doubling (40,000 U twice per week), and 5/9 (55%) of them achieved the erythroid response. CONCLUSION: Compared with data from the literature, this prospective study revealed that EPO-zeta is a safe and effective therapeutic option in low-risk MDS patients.

Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: the NEXT-in-CML study.

In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.

Prognostic assessment and treatment of primary gastric lymphomas: how endoscopic ultrasonography can help in tailoring patient management.

Endoscopic ultrasonography (EUS) has recently gained a pivotal role in the management of gastric lymphomas, especially in the diagnostic workup. Its accuracy and reliability have overcome those of other imaging techniques, such that it represents an invaluable tool for the management of gastric lymphomas. Although this technique is operator dependent, its application in large series has proved its reliability. Thus, it has generally been considered a useful tool for providing information crucial in deciding the treatment program, especially for mucosa-associated lymphoid tissue (MALT) lymphomas, for which EUS can provide an accurate evaluation of disease extension and treatment response probability. Limited-stage disease, confined to the submucosa, has a greater probability to respond to sole Helicobacter pylori eradication. In contrast, the value of EUS in response assessment and follow-up monitoring is still debated, with discordant opinions about its reliability and clinical advantages, because normalization of the EUS findings occurs with a considerable delay compared to the histologic evaluation. In the follow-up setting, preliminary data have indicated that persistently positive EUS findings in low-grade gastric lymphoma could represent a warning for a possible relapse. However, in high-grade gastric lymphoma, such findings do not have any clinical implications.

Treatment of elderly patients with chronic lymphocytic leukemia: an unmet cinical need.

In chronic lymphocytic leukemia (CLL), the most prevalent lymphoid malignancy in western countries, patients have a median age at diagnosis of 72 years. In the last few years, there has been remarkable progress in understanding the biology of CLL, the detection of molecular prognostic factors and the development of more effective therapies. However, many of the milestone studies were conducted in populations that were considerably younger than the average age of the CLL population. Today, the challenge is to improve management of elderly patients. In this population, outcome of treatment with newer highly effective therapies is often compromised by comorbidities and poor performance status. Decision on how elderly patients should be treated is thus a complex issue. The management of these patients should rely on the development of risk-stratified treatment strategies based on the assessment of individual functional status and the biologic characteristics of CLL. New single agents with reduced toxic effects (i.e., inhibitors of BCR signalling) that have achieved promising results in Phase I/II studies when available should modify the paradigm of the treatment of elderly patients with CLL.