Efficacy and safety of ibrutinib in mantle cell lymphoma: A systematic review and meta-analysis.

OBJECTIVES: Since the US Food and Drug Administration (FDA) approved ibrutinib to treat patients with refractory/relapsed mantle cell lymphoma (R/R MCL), it is used in clinical trials, whether as a single agent or in combination with other chemotherapy agents. The efficacy and safety of ibrutinib administration alone or in combinations have not been studied systematically. This study systematically reviewed the efficacy and safety of ibrutinib-containing regimens for the treatment of patients with MCL. EVIDENCE ACQUISITION: We performed a systematic search in PubMed, Cochrane CENTRAL, Embase, Web of Science, and Scopus. Then, a team of independent reviewers selected relevant studies and extracted the data. RESULTS: From a total of 1,436 studies, 12 trials were eligible. The overall response rates (ORRs) of patients with R/R MCL receiving single-agent ibrutinib ranged between 62.7% to 93.8%, and the ORRs of ibrutinib combinations ranged from 74 to 88%. In patients with newly diagnosed MCL receiving ibrutinib and rituximab, ORR ranged from 84 to 100%. The highest progression-free survival (PFS) was reported in patients receiving ibrutinib and rituximab (43 months). The meta-analysis performed on adverse events (AEs) demonstrated that single-agent ibrutinib had a high risk of bleeding, nausea, and diarrhea. CONCLUSION: Single-agent ibrutinib showed acceptable efficacy and safety in the treatment of patients with MCL. Moreover, combining ibrutinib with other agents such as rituximab, venetoclax, and ublituximab can increase its efficacy and reduce chemotherapy-induced resistance in most cases; however, in the case of combination therapy, patients need to be monitored more strictly in terms of AEs. In our review, the ibrutinib and rituximab combination showed promising results in patients with R/R MCL. Also, this combination showed favorable efficacy and safety in patients with newly diagnosed untreated MCL, making it a great candidate to be studied more in large and well-designed trials.

Melatonin in the prevention of cisplatin-induced acute nephrotoxicity: a randomized, controlled clinical trial.

Background and purpose: Cisplatin-induced nephrotoxicity (CisIN) remains the most dose-limiting adverse effect of its clinical use. The protective effects of melatonin on CisIN have been addressed in several non- clinical and animal studies. This study aimed at investigating the potential effects of melatonin on the prevention of CisIN in human. Experimental approach: Our study was a randomized controlled clinical trial, performed on 66 eligible patients in two groups of melatonin or control (no intervention). Melatonin was administrated daily at a dose of 20 mg for 5 days to the patients receiving cisplatin-containing regimens along with the standard protocol of CisIN prevention. Patient demographic information, blood and urinary indices of nitrogen, creatinine, and electrolytes such as sodium, potassium, magnesium as well as neutrophil gelatinase-associated lipocalin were measured in both groups at the baseline, 24 h and five days after melatonin administration. Findings/Results: Cisplatin administration resulted in significant magnesium and potassium loss in patients with cancer. In comparison with the control group, the prevalence of acute renal injury and the rate of urinary magnesium and potassium loss improved with melatonin administration; however, the results were not statistically significant. Tolerable side effects such as daytime drowsiness, nausea, and vomiting were reported in the melatonin group. Conclusion and implications: Although pretreatment with melatonin led to amelioration in urinary electrolyte loss due to CisIN, it failed to show a positive result on acute renal injury prevention. Future well-designed studies with a longer duration of follow-up, larger sample sizes, and higher doses of melatonin are warranted.

Efficacy and safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as perioperative chemotherapy treatments for resectable gastric cancer patients; a report from the middle east.

Background and purpose: This study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including epirubicin, cisplatin, 5-fluorouracil (ECF), docetaxel, cisplatin, 5-fluorouracil (DCF), leucovorin, 5-fluorouracil, oxaliplatin (FOLFOX), and 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) to identify the most effective chemotherapy regimen with less toxicity. Experimental approach: This retrospective cohort study (2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative mentioned chemotherapy regimens and followed for at least two years. The primary endpoint of this study was overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and R0 resection. Findings / Results: Of included patients, 21%, 33.7%, 24.3%, and 21% had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30-month follow-ups, OS was higher with the FLOT regimen in comparison with other regimens (hazard ratio = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank < 0.001). FLOT regimen showed 84. 4% ORR which was notably higher than other groups. Conclusions and implications: For resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients' OS and PFS versus ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.

Massive Splenomegaly: A Rare Presentation of Megaloblastic Anemia.

Megaloblastic anemia is a common disorder with various manifestations. Of the many causes, cobalamin or folate deficiency can eventuate into megaloblastic anemia. It can lead to pancytopenia and mild to moderate splenomegaly, but massive splenomegaly rarely seen in this situation. We describe a 39-year-old woman with marked enlargement of the spleen and pancytopenia that was found to have megaloblastic anemia. The splenomegaly and blood count resolved 4 months after initiation of vitamin B12 therapy. It is important to know massive splenomegaly may occur in megaloblastic anemia, and although it is rare, bur can reversible with early treatment.