BackgroundNovel treatments are needed to improve the poor prognosis of metastatic cancers. The ELEVATE Lung&UC study evaluated magrolimab plus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC), metastatic small cell lung cancer (mSCLC), and metastatic urothelial carcinoma (mUC).MethodsThis phase II, open-label, multi-arm study enrolled patients who had received 1–2 (mNSCLC, mSCLC) or 2–3 prior lines of therapy (mUC) in the locally advanced/metastatic setting. A safety run-in (SRI) cohort (mNSCLC/mSCLC/mUC) followed by a phase II cohort (three groups: mNSCLC, mSCLC, mUC) were planned. Primary endpoints were incidence of treatment-emergent adverse events (TEAEs; SRI and phase II) and objective response rate (ORR; phase II).ResultsThe SRI cohort (n = 9) had no dose-limiting toxicities. In phase II (mNSCLC, 29 patients; mSCLC, 42 patients; mUC, 26 patients), ORRs were 17.2% (mNSCLC), 4.8% (mSCLC), and 3.8% (mUC). Grade ≥3 magrolimab-related TEAE rates were 48.3% (mNSCLC), 47.6% (mSCLC), and 57.7% (mUC). A fatal TEAE suspected as magrolimab related (intracranial hemorrhage) occurred in one patient with mSCLC and brain metastasis (phase II). The study was closed early, which limited the interpretation of results due to short follow-up and limited endpoint maturity.DiscussionAdding magrolimab to docetaxel had manageable toxicity but no meaningful improvement in efficacy. These results provide insight into the safety and efficacy of anti-CD47–containing therapies and reinforce the need for treatments that address the unmet needs of patients with previously treated metastatic solid tumors.
Background The phase II ROSEWOOD study (NCT03332017) compared zanubrutinib plus obinutuzumab (ZO) with obinutuzumab monotherapy (O) in patients with relapsed/refractory (R/R) follicular lymphoma (FL) who had received two or more prior lines of systemic therapy. Median progression-free survival (PFS) was longer with ZO versus O [28.0 versus 10.4 months; hazard ratio 0.50, 95% confidence interval (CI) 0.33-0.75]. Materials and methods In this post hoc analysis, an intra-patient comparative analysis was carried out using the growth modulation index (GMI) to analyze the efficacy of ZO versus the last prior treatment received by patients in the ROSEWOOD study. A GMI of ≥1.33 was used as a threshold for significant clinical activity. Results In the overall population, median GMI was 2.7 (95% CI 1.6-4.9) in the ZO arm and 0.9 (95% CI 0.5-1.7) in the O arm. Analysis in subgroups of clinical interest in the ZO arm showed that PFS was longer with ZO than with the last prior treatment, and median GMI was ≥1.33 in all subgroups tested. Overall, PFS had improved (GMI ≥1.33) in >60% of patients with R/R FL who received ZO versus their last prior treatment. Conclusions This GMI analysis further supports the benefit of ZO as a novel therapeutic option for patients with R/R FL.
Purpose This study aimed to evaluate the real-world effectiveness and feasibility of low-dose radiation therapy (LDRT) for peripheral joint osteoarthritis (OA) in a United States community oncology setting, focusing on pain, function, and analgesic outcomes. Methods and Materials We retrospectively analyzed 30 consecutive patients (55 joints) treated with LDRT (3 Gy in 6 fractions; 0.5 Gy per fraction) for OA. Pain was assessed using a 0 to 10 numeric rating scale. Global improvement was captured with the von Pannewitz score (0-4; lower = greater improvement). Analgesic change was abstracted from the medical record. Paired tests compared pre- and posttreatment outcomes. Results Mean baseline pain was 8.1 ± 1.4, improving to 3.5 ± 1.7 at early follow-up (Δ−4.6; P < .001). von Pannewitz score indicated improvement in 92% of treated joints. Twenty-three percent of patients reduced analgesic use; none required analgesic escalation. All patients completed treatment without interruptions, and no acute toxicities were recorded. Conclusions In a community oncology setting, LDRT was feasible and associated with clinically meaningful reductions in pain and analgesic use for peripheral joint OA. These findings support prospective trials to validate benefits and define optimal patient selection and retreatment strategies.
BACKGROUND:ABM-1310 is an investigational, orally bioavailable BRAF V600 inhibitor with high blood-brain barrier (BBB) penetration. PATIENTS AND METHODS:This first-in-human, phase I trial evaluated patients with BRAF V600-mutated advanced solid tumors, including brain metastases (≤3 cm) and primary central nervous system (CNS) tumors. Patients received ABM-1310 monotherapy [25-250 mg twice a day (b.i.d.); Parts A/C] or in combination (ABM-1310 : 100-200 mg b.i.d.; cobimetinib 60 mg once a day, days 1-21 of each 28-day cycle; Part B). Primary endpoints included safety, tolerability, and maximum tolerated dose (MTD); secondary endpoints included pharmacokinetic (PK) profile and antitumor activity per RECIST v1.1 or Response Assessment in Neuro-Oncology criteria. RESULTS:Fifty-three patients were enrolled (36 monotherapy, 17 combination). Median age was 55 years; 68% were male, 72% had ≥3 prior treatment lines, 92.5% had BRAF V600E mutations, 75% of patients had received prior BRAF plus MEK inhibitor therapy, and 7.5% had BRAF inhibitor monotherapy. Common tumor types included melanoma (47%), glioblastoma (17%) and thyroid cancer (13%). The most frequent treatment-related adverse events were QT prolongation and rash. Dose-limiting toxicities (DLTs) occurred in 6/37 patients (16.2%), all at doses ≥150 mg. All DLTs involved asymptomatic electrocardiogram QT prolonged, with two cases presenting co-occurring toxicities: one with rash and one with renal failure-establishing the MTD at 200 mg b.i.d. Among 50 efficacy-evaluable patients, the objective response rate (ORR) was 12% and disease control rate (DCR) was 64%. Median progression-free survival was 4.96 months (2.07-8.31) and median overall survival was 24.48 months 11.6-not estimable. In patients with primary CNS tumors (n = 13), ORR was 23.1% and DCR 76.9%. PK analyses showed dose-proportional exposure and moderate accumulation. CONCLUSIONS:ABM-1310 showed a favorable safety profile and encouraging intracranial activity. These findings support continued evaluation for CNS tumors and in cancer patients with prior BRAF inhibitor exposure.
Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage.
