Search

Novel treatment strategies are needed for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell-engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414.

PurposeMost myeloablative regimens before stem cell transplant involved total body irradiation (TBI). Pulmonary complications from TBI contribute to treatment-related mortality and toxicity. We report the rate of acute respiratory complications after TBI at our institution. In an exploratory analysis, we investigated differences in dosimetry between patients who did and did not experience respiratory complications.Methods and materialsIn this single institution retrospective study, 49 patients received TBI from 2016 to 2018 and had dosimetry data available for analysis. Patients were prescribed 1200 cGy to be delivered over 6 fractions. Lung doses were limited using custom lung blocks. Clinical lung complications (eg, coughing and shortness of breath) were reviewed for the hospitalization period during transplant, at 4 months after transplant, and at 1 year after transplant. Supplemental oxygen use during the hospitalization period was also reported. Median anterior-posterior diameter at the umbilicus, body mass index, and lung doses were compared between patients with and without respiratory complications using a Mann-Whitney U test.ResultsDuring the hospitalization period, 14% (n = 7) of patients used supplemental oxygen administered by nasal canula and 16% (n = 8) experienced respiratory symptoms. At the 4-month follow-up, 16% (n = 8) of patients had documented respiratory symptoms. Respiratory symptoms were grade 1 to 2 except for one grade 3 attributed to infection during the hospitalization period and another grade 3 due to infection during the 4-month follow-up. At 1-year post-TBI, 4% (n = 2) of patients reported grade 1 to 2 chronic cough. Patients with respiratory complications at the 4-month follow-up had a larger umbilical anterior-posterior diameter (31.5 cm vs 26.5 cm, P = .01) and body mass index (34.5 kg/m2 vs 29.7 kg/m2, P = .02) than patients without respiratory complication. Respiratory complications were not associated with higher lung doses.ConclusionsThere was no respiratory-related mortality using the individualized planning technique described here. Acute and chronic respiratory complications were minor, with the most significant intervention requiring antibiotics for respiratory infection.

Summary: Philadelphia chromosome (Ph)‐like acute lymphoblastic leukaemia (ALL) is a high‐risk subtype with a gene expression profile similar to Ph‐positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph‐like ALL, this single‐centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph‐like, 89 (33.2%) Ph‐positive, and 111 (41.4%) Ph‐negative. Ph‐like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph‐negative ALL, Ph‐like achieved worse event‐free survival (EFS) (HR = 1.66; 95% CI 1.12–2.46; p = 0.012), whereas Ph‐positive had improved EFS (HR = 0.60; 95% CI 0.38–0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35–0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease‐free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1‐year pre‐HSCT had improved DFS (HR = 0.43; 95% CI 0.20–0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09–0.75; p = 0.13). In conclusion, our data suggest that Ph‐like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph‐negative ALL. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality inHSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] posthaploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/ Tac/MMF)asGVHDprophylaxis.Aliver biopsyconfirmedthediagnosis ofGVHD,while other possible etiologieswere excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment,we decided to administer 1,000mg/m2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepaticGVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting. [ABSTRACT FROM AUTHOR]

BACKGROUND: At a time when coronavirus variants are persistently emerging, effective strategies to protect immunocompromised patients with cancer from COVID-19 and its complications are critically needed. Because tixagevimab plus cilgavimab is a novel drug combination, there is a lack of real-world data that reveal the safety and efficacy data for patients with cancer. Only 7% of patients had an active cancer or history of cancer in the phase 3 PROVENT study, with 3% of the total population receiving immunosuppressive therapy. OBJECTIVE: To evaluate the efficacy of tixagevimab plus cilgavimab in patients with cancer as pre-exposure prophylaxis to COVID-19 in the reduction of positive COVID-19 cases, hospitalizations, inpatient length of stay, and mortality. METHODS: This retrospective study evaluated the incidence of COVID-19 among adults with malignancies who did or did not receive tixagevimab plus cilgavimab between January 4, 2022, and December 31, 2022. The secondary study outcomes included hospitalization, hospital length of stay, and mortality resulting from COVID-19, as well as the incidence of tixagevimab plus cilgavimab–related adverse events. To validate the accurate reporting of positive COVID-19 cases, texted and emailed surveys were distributed by the Keck School of Medicine of the University of Southern California (USC) research department. RESULTS: In a single-center, retrospective review of 13,522 patients with cancer who had a visit within the USC system in 2022, 305 (2.3%) patients received tixagevimab plus cilgavimab. After propensity score matching, 304 patients of the 13,522 were in the tixagevimab plus cilgavimab group and 304 patients of the 13,217 patients with cancer who did not receive tixagevimab plus cilgavimab were in the control group. The overall median patient age was 66 years (range, 19-96 years). Treatment with tixagevimab plus cilgavimab significantly decreased the risk for COVID-19 between January 2022 and June 2022 (risk ratio, 0.23; 95% confidence interval, 0.03-0.74; P=.038). A total of 32 (10.5%) patients in the tixagevimab plus cilgavimab group tested positive for COVID-19 versus 45 (14.8%) patients in the control group. Between January 2022 and June 2022, 2 patients were COVID-19 positive in the tixagevimab plus cilgavimab group versus 18 patients in the control group, which increased in July 2022 to December 2022 to 30 cases and 27 cases, respectively. Among the COVID-19–positive patients, 4 (1.3%) who received tixagevimab plus cilgavimab were hospitalized versus 11 (3.6%) patients in the control group (P=.114). The median lengths of stay were 2 days (range, 2-7) and 4 days (range, 1-15 days), respectively (P=.906). Adverse events occurred in 3 (3.4%) patients in the tixagevimab plus cilgavimab group and included nausea, vomiting, blurry vision, and headache. The COVID-19–unrelated deaths included 10 (3.4%) in the tixagevimab plus cilgavimab group and 22 (8.5%) in the control group. There was 1 COVID-19–related death in the control group. CONCLUSION: Treatment with tixagevimab plus cilgavimab was effective in reducing COVID-19 infection during the first half of 2022 but was unsuccessful in reducing COVID-19 infection in the latter half of 2022, likely as a result of high mutation rates of the coronavirus and the medication’s inability to adapt to newer strains of the virus. However, there was a clinically meaningful reduction in hospitalization and in the severity of COVID-19 in a small number of patients who received tixagevimab plus cilgavimab in our study. Although tixagevimab plus cilgavimab is not currently approved for use in the United States, our findings provide a better understanding of how the use of tixagevimab plus cilgavimab, and potential future monoclonal antibodies, play a role in minimizing COVID-19–related complications in patients with cancer. [ABSTRACT FROM AUTHOR]