This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab’s potential for severe infectious complications, despite its promise in treating RRMM.

Gastric cancer is one of the most common cancers worldwide. While relatively uncommon in the United States, worldwide it is the 5^th most common cancer diagnosed. Almost half of patients present with locoregional disease. Even with advanced surgical techniques and adjuvant perioperative treatment the prognosis for patients in this cohort is still dismal. Perioperative chemotherapy and/or radiation have been used in the last several decades in an attempt to improve outcomes in locally advanced resectable gastric cancer. In this article, we will review the development of these multimodal treatment strategies over the past two to three decades. We will compare these treatment modalities and their impact on survival outcomes. We will review the evidence for perioperative chemotherapy and radiotherapy, used in isolation and in combination. We will evaluate the evidence for these various treatment strategies and discuss how this impacts the current guidelines and recommendations. While advanced locoregional gastric cancer continues to carry significant mortality, several recent studies have added to the armament of treatment options and have seen significant improvement in progression free and overall survival in this patient population. Ongoing studies into perioperative management continue to investigate alternative treatment options and best practice for locally advanced resectable gastric cancer.

Background: Patients with hematologic malignancies (HMs) receive more disease directed care at the end of life (EOL) and often die in the hospital. The impact of early palliative care (PC) consultation on EOL quality outcomes in HMs has not been well described. Objectives: In 2017 we embedded a PC specialist within our inpatient malignant hematology team at our hospital in Providence, Rhode Island to facilitate the use of early PC. We sought to determine if this practice was accompanied by a shift in EOL outcomes. Design/Setting: We conducted a retrospective review of patients diagnosed with acute myeloid leukemia (AML) at our institution in the two years before (Cohort A) and after (Cohort B) insertion of a PC specialist. We identified patients who received a PC consultation and whether it was early or late. We then examined EOL quality outcomes: hospitalizations and intensive care unit (ICU) admissions in the last 30 days of life, chemotherapy use in the last 14 days of life, use of hospice, and death out of hospital. Results: Among 139 AML patients, 46 in Cohort A and 93 in Cohort B, we identified 34 and 47 decedents in each cohort, respectively. There was no significant improvement in EOL outcomes between Cohort A and B or among patients receiving early PC ( p > 0.05); however, PC in general across all cohorts was associated with significant increase in hospice use and fewer ICU admissions ( p = 0.016 and 0.0043, respectively). Conclusion: Earlier PC consultation in AML was not significantly associated with improvement in EOL quality outcomes; however, PC use in general was with improvement in use of hospice and ICU utilization. Further studies are needed to more definitively examine the relationship between early PC and EOL outcomes in patients with HMs and to examine non EOL outcomes such as patient experience and quality-of-life measures.

Background:Mosunetuzumab (Mosun) is a bispecific CD20xCD3 antibody approved for the treatment of follicular lymphoma (FL) after ≥2 lines of therapy. In that setting, Mosun provides 60% complete response (CR) rate despite prior immunosuppressive therapy [Budde et al., Lancet Oncol 2022]. BrUOG-401 (NCT04792502) is an investigator-initiated, multicenter, single arm, phase 2 clinical trial testing the hypothesis that administering Mosun for previously untreated FL or marginal zone lymphoma (MZL) will result in a higher CR rate than standard chemoimmunotherapy. Additionally, selective immune augmentation using low-dose lenalidomide (Len) may improve response for patients who do not attain CR on interim assessment. Here, we present the pre-planned interim efficacy analysis of this trial. Methods:Patients with previously untreated, high-burden or symptomatic FL or MZL received subcutaneous Mosun for 8 planned cycles (C) with step-up dosing in C1 (day 1: 5mg, day 8 & 15: 45 mg; then 45mg on day 1 of C2-C8). Patients who attained only partial response [PR] or stable disease at interim assessment after C4 received the addition of Len augmentation (10mg daily, continuously) during C5-C8, with an optional extension up to C12. The primary endpoint is the CR rate at the end of therapy, assessed using PET-CT-based Lugano criteria [Cheson et al., JCO 2014]. However, for the primary hypothesis evaluation, we used CT-based criteria to test the superiority of the CR rate over the historical 53% CR rate reported (using CT criteria only) with bendamustine/rituximab chemotherapy in the RELEVANCE trial (Morschhauser et al., NEJM 2018). This pre-planned interim analysis occurred after 25 patients were evaluable for response, with futility stopping rule if ≤13 CR's were observed. Secondary objectives include safety, overall response rate (ORR), progression-free and overall survival (OS), as well as the rate of conversion from PR to CR on Mosun+Len augmentation. Adverse events (AE) were graded using CTCAE v5 criteria, and cytokine release syndrome (CRS) using the 2019 ASTCT criteria. Results:As of July 2024, 37 patients (median age 65, range 30-89; 58% women; 86% white non-Hispanic) were enrolled, including 22 (59%) with FL and 15 (41%) with MZL. The lymphoma stage was 2 in 14%, 3 in 22%, and 4 in 64%. Among the FL patients, FLIPI was low in 6, intermediate in 7, and high in 9. Two patients discontinued treatment (1 for AE, 1 for progression) before completing C8. The most common AE on treatment included injection site reaction (n=18 [49%]; grade [G]1 in 17, G2 in 1), fatigue (43%; G1/2 in 15, G3 in 1), and rash (38%; G1/2 in 11, G3 in 3). Other G3/4 AE's (in ≥2 patients) included Pneumocystis jirovecii pneumonias (PJP, occurred during C2 and C3), hypertension, weakness, pain, and neutropenia (each in n=2). There were 6 (16%) CRS events, all G1 and during C1, and all resolved. One patient received tocilizumab. No G3/4 toxicities attributed to Len were observed. At the data cutoff, 25 patients were evaluable for response. Using Lugano criteria, the CR rate was 82% (95% confidence interval [CI], 60-95%), and the ORR was 86% (95%CI, 65-97%). The CR rate was 80% for FL and 86% for MZL. Six patients received Len augmentation and 3 of the evaluable 4 converted to CR, whereas one had (after initial PR) progressive disease with biopsy-proven histologic transformation. With short follow up (median 5.8 months), no recurrence was observed among patients with CR; OS is 100%. The 14 observed CR's (using CT-based criteria) satisfied the interim analysis criterion for the pre-planned two-stage design. Flow cytometry demonstrated, apart from a rapid B-cell depletion, a temporary decrease in circulating TEMRA CD8+ T-cells and a significant increase in LAG3 and PD-1 expression at C2. At the end of C4, patients not attaining early CR showed significantly lower counts of NK cells (P=0.009) and no effector memory T-cell expansion. These differences resolved after 4 cycles of Mosun+Len augmentation. Conclusions:Fixed-duration subcutaneous Mosun resulted in a high CR rate during first-line treatment of FL and MZL with limited toxicity, including only 16% rate of G1 CRS, and similar CR rates in FL and MZL on this initial assessment. Selective immune augmentation using low-dose continuous Len was safe and may facilitate conversion to CR for slow early responders. Study enrollment continues and both safety and efficacy analyses with longer follow-up will be presented.

Background: Newly diagnosed multiple myeloma patients have many available treatment options. While lenalidomide, bortezomib, and dexamethasone (RVD) is the preferred initial treatment for many patients, several other agents may provide similar efficacy with less toxicity and improved ease of administration. Methods: We evaluated the safety and efficacy of the all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone with the use of metronomic cyclophosphamide dosing in the treatment of patients with newly diagnosed multiple myeloma. Results: The study was stopped prior to planned enrollment due to slow recruitment, with 12 patients available for final analysis. The overall response rate was 58.3% with 2 patients achieving a very good partial response (16.7%) and 5 patients achieving a partial response (41.7%). Median progression-free survival was 16 months, and median overall survival was 43 months. There were no episodes of grade 3 or greater peripheral neuropathy. Grade 3 or greater dermatologic toxicity was experienced in 50% of patients. Conclusion: Although limited enrollment prevented full efficacy evaluation, our data do not support further study of metronomic cyclophosphamide in combination with ixazomib and dexamethasone in the treatment of newly diagnosed multiple myeloma. The activity of this regimen in the relapsed/refractory setting requires further study (ClinicalTrials.gov Identifier: NCT02412228).