BACKGROUND: Infliximab and vedolizumab are widely used to treat Crohn\'s disease (CD) and ulcerative colitis (UC).
OBJECTIVE: This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC.
METHODS: Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis.
RESULTS: Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks.
CONCLUSIONS: Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

Ustekinumab has two alternative drug maintenance intervals for inflammatory bowel disease (IBD), every 8 weeks (Q8W) and every 12 weeks (Q12W). The current study aimed at evaluating the comparative efficacy and safety of the two maintenance intervals in patients with IBD. A systematic search on PubMed, Web of Science, Cochrane Library, and EMBASE was carried out. The relative risk (RR) was pooled for efficacy and safety outcomes between the two intervals at various follow-up time points, categorized as short term (less than 44 weeks), medium term (about 92 weeks), and long term (about 152 weeks). A total of 14 studies with 1448 patients were included. Q8W didn\'t result in a remarkably higher proportion of clinical remission compared to Q12W at short term (RR, 0.99; 95% CI, 0.83-1.16), medium term (RR, 1.05; 95% CI, 0.91-1.20), and long term (RR, 1.07; 95% CI, 0.91-1.26). Similarly, no substantial differences exist at short term in clinical response (RR, 1.00; 95% CI, 0.85-1.17), endoscopic remission (RR, 0.97; 95% CI, 0.26-3.69), and histologic improvement (RR, 1.13; 95% CI, 0.93-1.36) between the two intervals. For safety outcomes, the RR values for any adverse events in the short, medium, and long term were 1.10 (95% CI, 1.00-1.21), 1.14 (95% CI, 1.08-1.20), and 1.12 (95% CI, 1.07-1.17) for Q8W versus Q12W. Finally, we conclude that ustekinumab maintenance therapy administered every 8 and 12 weeks showed similar effectiveness in achieving efficacy outcomes in IBD patients, and most safety outcomes were significantly better for Q12W during the maintenance phase.

BACKGROUND: Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings.
METHODS: A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic.
RESULTS: We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2 = 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9).
CONCLUSIONS: Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects.

Limited data exist on the management of patients with locally advanced (aPC) or metastatic pancreatic (mPC) cancer who achieve stable disease/response after first-line chemotherapy. In this setting, maintenance therapy is important to minimize toxicity while preserving survival benefits. The aim of this study is to conduct a narrative review of the evidence available on the topic and present the results of a retrospective case series of patients with aPC or mPC who received maintenance therapy following a good response to induction chemotherapy. Olaparib is the only drug approved for maintenance therapy in patients with metastatic pancreatic cancer and germline Breast Cancer gene mutation. Data from several trials, including the phase II PANOPTIMOX-PRODIGE35 trial, showed clinical benefit from the use of 5-fluorouracil (5-FU) as maintenance. We also conducted a case series including 12 patients who received FOLFIRINOX as induction chemotherapy for aPC or mPC followed by fluorouracil (5-FU) or FOLFIRI maintenance therapy. Median progression-free survival is 22.13 months which is higher than that reported in the literature, which ranges between 5 and 10.6 months. Although further conclusions cannot be drawn because of the small sample size, the results are promising and encourage further exploration of this topic in larger prospective trials.

Recent advances in the diagnosis and management of multiple myeloma (MM) have improved patient outcomes. This progress in our understanding of MM has resulted in continuous suppressive therapy concepts, including induction, high dose chemotherapy with autologous stem cell transplantation (ASCT), consolidation, and maintenance therapy. The foundation of maintenance therapy has been with lenalidomide. Other novel immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and targeted monoclonal antibodies have also contributed to this evolution.
This review summarizes the outcomes from phase II/III trials with long-term lenalidomide maintenance therapy alone or in combination with other agents in post-ASCT and non-transplant settings for newly diagnosed patients with MM. We review recent data considering a combination with newer medications and ongoing trials. We also review the optimal duration, MRD negativity rate, and safety and tolerability aspects of lenalidomide maintenance therapy. This review aims to present the current and emerging clinical evidence that supports using lenalidomide as a backbone for maintenance therapy in patients with MM.
There is increasing evidence to support lenalidomide as the backbone of combination therapy in the maintenance setting.

OBJECTIVE: Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year.
METHODS: Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients.
CONCLUSIONS: Approximately 34 920 people in the US and 155 688 people worldwide are diagnosed with multiple myeloma each year. Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent and dexamethasone followed by treatment with autologous hematopoietic stem cell transplantation, and maintenance therapy with lenalidomide are among the treatments considered standard care for eligible patients.

Older patients encompass about 75 % of patients with acute myeloid leukemia (AML). Today therapeutic options to prevent relapse in older patients who managed to achieve complete remission (CR) after intensive chemotherapy are scarce. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-CR maintenance therapy.
We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with hypomethylating agents (HMA) vs. observation, conventional care or placebo in older patients with AML who are not candidates for allogeneic hematopoietic transplantation (allo-HCT). We searched Cochrane Library, PubMed and conference proceedings up to August 2021.
Six trials were included. Treatment with hypomethylating agents significantly improved overall survival (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 30 %), and disease control (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 0). A significant decrease was seen in both one year mortality (Risk Ratio [RR] 0.61, 95 % CI 0.48 to 0.77, I2 = 0) and mortality at the end of follow-up (RR 0.77, 95 % CI 0.67 to 0.88, I2 = 0). The rate of relapse at 6 months and at one-two years was lower in the HMA arm vs. control (RR, 0.59; 95 % CI, 0.47-0.72; RR, 0.74, I2 = 0; 95 % CI 0.69 - 0.91, I2 = 41 %, respectively). HMA were associated with a statistically non-significant increase in the risk of serious adverse events (RR 3.44, 95 % CI 0.93-12.74, I2 = 80 %).
Our meta-analysis shows that in older patients who are not candidates for allo-HCT, maintenance therapy with HMA improves OS and disease control without a statistically significant increase in adverse events.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with a poor prognosis. Recently, an immunotherapy strategy represented by programmed cell death 1 (PD-1) inhibitors has been applied to the systemic treatment of advanced iCCA. However, immunotherapy combined with chemotherapy as first-line maintenance therapy was rarely reported. Our report presented an advanced iCCA patient who had a dramatic response to the PD-1 inhibitor sintilimab combined with gemcitabine plus cisplatin as the first-line therapy and sintilimab combined with capecitabine as maintenance therapy, yielding an ongoing progression-free survival of 16 months.

The therapeutic role of immune checkpoint inhibitors (ICIs) has represented the cutting edge of clinical research in upper gastrointestinal (GI) malignancies, with these agents now included in the armamentarium of treatment options for advanced gastric and esophageal cancers.
We performed a systematic literature review and pooled analysis to map out the currently available robust clinical evidence for the use of ICIs in upper GI cancers. Immunotherapy (IO), either as monotherapy or in combination with chemotherapy, and its role in first-line, maintenance, and second-line settings, as well as in specific clinical and biological subgroups, were critically appraised. All statistical tests were 2-sided.
ICIs, in combination with chemotherapy, have provided statistically significant overall survival benefit in the first-line setting in gastric and gastro-esophageal adenocarcinomas (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.76 to 0.90, P < .001; based on 4 studies) and esophageal squamous cell carcinoma (HR = 0.72, 95% CI = 0.64 to 0.81, P < .001; based on 3 studies), albeit with heterogeneous efficacy according to biomarker expression. Patients with esophageal squamous cell carcinoma, and in particular high programmed cell death ligand-1 expression, derive survival benefit when treated with IO in the second-line setting (HR = 0.74, 95% CI = 0.68 to 0.82, P < .001; for any level of programmed cell death ligand-1 expression). Clinical trials interrogating the combination of IO with chemotherapy in second-line treatment should be seriously considered in upper GI adenocarcinomas. The role of maintenance IO after initial disease control is still unclear and cannot be recommended. Impressive response rates and survival benefit from IO have been reported in patients with microsatellite instability-high tumors (HR = 0.33, 95% CI = 0.19 to 0.57, P < .001), and this warrants further prospective biomarker-driven studies.
IO is changing the treatment landscape in upper GI malignancies. The rapidly developing evidence in the field needs to be critically appraised while further validation of the existing information from ongoing trials is awaited.

We previously reported elsewhere of a follicular lymphoma patient suffering from persistent COVID-19 pneumonia that was still ongoing at 2 months after onset.
We provide a follow-up report of the case along with a literature review of immunocompromised lymphoma patients experiencing prolonged COVID-19 infections.
Although requiring a full 1 year, the presented case eventually achieved spontaneous resolution of COVID-19 pneumonia. Anti-SARS-CoV-2 antibodies could not be detected throughout the disease course, but COVID-19-directed T-cell response was found to be intact. The patient also developed secondary immune thrombocytopenia subsequent to COVID-19 pneumonia. We found 19 case reports of immunocompromised lymphoma patients with prolonged COVID-19 infections in the literature. All 5 patients who died did not receive convalescent plasma therapy, whereas resolution of COVID-19 infection was achieved in 8 out of 9 patients who received convalescent plasma therapy.
We demonstrate through the presented case that while time-consuming, resolution of COVID-19 infections may be achieved without aid from humoral immunity if cellular immunity is intact. Immunocompromised lymphoma patients are at risk of a prolonged disease course of COVID-19, and convalescent plasma therapy may be a promising approach in such patients.