Cancer最新文献

Background

Survival for patients with high-risk neuroblastoma remains poor despite current-era multimodality treatment that includes postconsolidation GD2-directed immunotherapy. Given the promising responses in patients who receive dinutuximab-based chemoimmunotherapy in the relapsed setting, the Children’s Oncology Group ANBL19P1 study evaluated the feasibility of administering irinotecan, temozolomide, dinutuximab, and sargramostim after frontline consolidation with tandem autologous stem cell transplantation (ASCT).

Methods

Patients with high-risk neuroblastoma who received induction therapy followed by tandem ASCT and had no evidence of progressive disease (PD) were eligible. Treatment included five 28-day cycles of temozolomide and irinotecan (days 1–5), dinutuximab (days 2–5), and sargramostim (days 6–12). Isotretinoin (days 8–21) was given during cycles 1–6. Therapy was deemed feasible if the 95% confidence interval placed on the percentage of patients that completed five cycles of chemoimmunotherapy without PD within 30 weeks contained 75% in the absence of excessive toxicity. Event-free survival and overall survival were determined from the time of enrollment.

Results

Forty eligible patients enrolled, and 35 (87.5%; 95% confidence interval, 73.9%–94.5%) completed five cycles without PD within 30 weeks, meeting the feasibility threshold. No unacceptable toxicities occurred on protocol therapy, including no toxic deaths. Five patients discontinued therapy early because of physician determination (n = 2), patient/parent refusal of further therapy (n = 2), and PD (n = 1). The 2-year event-free and overall survival rates were 82.5% ± 6.1% and 92.5% ± 4.2%, respectively.

Conclusions

The administration of chemoimmunotherapy in the postconsolidation setting after tandem ASCT is feasible and tolerable. Future studies will be needed to define the population most likely to benefit from this augmented postconsolidation therapy.

Introduction

Standardized incidence rates of multiple myeloma (MM) are higher among males than females, suggesting that male sex is an important risk factor for MM, which may affect disease etiology, pathogenesis, and clinical presentation.

Methods

The association of sex with the prevalence of clinical features and chromosomal abnormalities was evaluated among 850 patients with newly diagnosed MM enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE). Risk estimates were calculated using prevalence odds ratios (OR) and corresponding 95% CIs from logistic regression adjusted for confounders.

Results

Male patients with newly diagnosed MM by comparison with females, were more likely to have International Staging System stage III disease (odds ratio [OR] = 2.05; 95% CI, 1.22–3.46; p = .007), high serum monoclonal protein (≥3 g/dL; OR = 1.72; 95% CI, 1.15–2.56; p = .008), κ light chain disease (OR = 1.60; 95% CI, 1.11–2.30; p = .01), and more end-organ damage (OR = 1.24; 95% CI, 1.02–1.50; p = .03) including impaired renal function (OR = 1.71; 95% CI, 1.12–2.61; p = .01) and lytic lesions (OR = 1.97; 95% CI, 1.01–3.85; p = .05) and were less likely to have osteopenia (OR = 0.59; 95% CI, 0.36–0.98; p = .04) and light chain only disease (OR = 0.63; 95% CI, 0.41–0.95; p = .03) after adjusting for race, age, body mass index, education, income, smoking, and alcohol use. Significant interactions of age on the association of male sex with the prevalence of involved to uninvolved free light chain ratio ≥100 (p = .01) and any copy number abnormality (p = .04) were also observed.

Conclusion

These novel findings suggest that male patients with newly diagnosed MM have a greater tumor burden.

Background

The number of cancer survivors aged older than 65 years is rising rapidly. Current evidence-based exercise guidelines lack specific guidance for older cancer survivors as a result of insufficient evidence. An expert panel was convened to develop consensus-based recommendations for exercise in older cancer survivors.

Methods

The development of recommendations was guided by the Grading of Recommendations Assessment, Development, and Evaluation Evidence-to-Decision framework for good practice statements. The panel drew from the available literature, a Delphi survey of exercise and health professionals, other exercise guidelines, clinical and research expertise, and interest-holder input provided by a community advisory board of older cancer survivors and caregivers (n = 11). Recommendations had to be deemed accessible (i.e., no added barriers) to older cancer survivors and feasible to implement. The panel voted on the strength of the recommendation for or against each statement, with consensus set at 85% agreement.

Results

Consensus was reached on 11 recommendations covering the following areas: medical evaluation/clearance for exercise, pre-exercise assessment, exercise prescription, exercise tolerance and safety, exercise delivery, and behavioral support. The recommendations aimed to promote engagement in and uptake of appropriately prescribed exercise programming by older cancer survivors, while keeping barriers and risks as low as possible.

Conclusions

Older cancer survivors can benefit from appropriately prescribed exercise, which should be an essential component of their cancer care. Exercise and health professionals need to consider the unique needs of older cancer survivors to ensure that exercise is safe and effective for this population, while also reducing barriers to reach as many people as possible.

Background

Primary central nervous system lymphoma (PCNSL) is an aggressive, immune-privileged, large B-cell lymphoma with limited frontline treatment options.

Methods

This study was an open-label, single-arm, phase 1/2 trial evaluating orelabrutinib combined with an anti–programmed cell death protein-1 (PD-1) antibody and a non-methotrexate chemotherapeutic agent (fotemustine) in patients with newly diagnosed PCNSL (ClinicalTrials.gov identifier NCT04831658). Orelabrutinib was tested at three dose levels (100, 150, and 200 mg), and the recommended phase 2 dose was determined as 150 mg. In phase 2, patients received orelabrutinib 150 mg orally once daily, a PD-1 inhibitor 200 mg intravenously on day 1, and fotemustine 100 mg/m² intravenously on day 2 every 21 days for six cycles. The primary endpoint was the objective response rate.

Results

From February 2021 to October 2023, 31 patients (median age, 62 years; age range, 37–70 years) were treated, and 27 were evaluable for efficacy. The objective response rate was 85.2% (complete response, 66.7%; partial response, 18.5%). The median progression-free survival was 9.4 months (95% confidence interval, 5.4–13.4 months), and the median overall survival was 22.8 months (95% confidence interval, 1.1–44.5 months). The 1-year and 2-year overall survival rates were 68.0% and 48.0%, respectively. The most common grade 3/4 adverse events were thrombocytopenia (45.2%), pulmonary infection (38.7%), and leukopenia (25.8%).

Conclusions

Orelabrutinib combined with PD-1 blockade and fotemustine demonstrated high antitumor activity with manageable toxicity, supporting its potential as a frontline regimen for PCNSL.

Background

Circulating tumor DNA (ctDNA) is a valuable biomarker for assessing treatment response and molecular residual disease. In advanced esophageal and gastric cancer (gastroesophageal cancer [EGC]), ctDNA dynamics remain poorly understood. The authors investigated ctDNA in patients with advanced EGC to evaluate its clinical utility.

Methods

This was a multi-institutional, retrospective analysis of 200 patients with recurrent/metastatic EGCs who underwent commercial ctDNA testing using a personalized, tumor-informed assay (Signatera; Natera, Inc.). Patients were divided into cohort A (N = 36; stage I–III with recurrence) or cohort B (N = 164; metastatic at diagnosis). Longitudinal ctDNA dynamics were correlated with clinical and radiographic findings.

Results

In cohort A, 31 of 36 patients (86.1%) had ctDNA collected ≤90 days before recurrence; of these, 25 of 31 patients (80.65%) were ctDNA-positive before recurrence. In cohort B, baseline ctDNA was available for 29 of 164 patients (17.68%), and all 29 were ctDNA-positive. Among 52 patients who had on-treatment ctDNA assessments, 62 treatment lines were analyzed (N = 6 in cohort A; N = 46 in cohort B). All who remained ctDNA-negative throughout treatment (Neg-Neg) showed treatment benefit (n = 6 of 6). Those who converted to ctDNA-positive (Neg-Pos) progressed (n = 2 of 2). Among ctDNA-positive patients (Pos-Pos), 27 of 40 (67.5%) showed treatment benefit, whereas 13 of 40 (32.5%) progressed. Patients who cleared ctDNA (Pos-Neg) had favorable outcomes (12 of 14 patients; 85.7%). A decrease >90% in ctDNA levels among Pos-Pos patients was linked to superior progression-fee survival. Grouping treatment lines into favorable (Neg-Neg, Pos-Neg, and Pos-Pos with >90% decrease) versus unfavorable (Neg-Pos and Pos-Pos with a <90% decrease or an increase) had significantly improved progression-free survival in the favorable group (p < .0001).

Conclusions

ctDNA dynamics predicted progression and may guide treatment or imaging. ctDNA offers a minimally invasive, cost-effective adjunct to radiographic surveillance.

Background

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic neoplasm that expresses CD123, is often observed in the bone marrow (BM), as well as skin, blood, and viscera. Tagraxofusp, a first-in-class CD123-targeted therapy, is the only drug approved to treat BPDCN.

Methods

The authors conducted a post hoc analysis of the pivotal phase 2 trial to evaluate hematopoietic and BM effects of first-line tagraxofusp treatment (12 µg/kg per day on days 1–5 of a 21-day cycle) over time.

This trial was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier NCT02113982).

Results

Of 66 treatment-naive patients in this analysis, 32 had baseline BM disease, and 34 had no BM disease. Over the course of tagraxofusp monotherapy treatment, neutrophil levels restored to normal, mirrored by a decreasing incidence of neutropenia and granulocyte-colony–stimulating factor administration from baseline with each cycle of treatment. Similarly, platelet counts recovered during treatment, whereas thrombocytopenia incidence and requirement for platelet transfusions decreased from baseline. Hemoglobin levels improved during tagraxofusp treatment, correlating with a decrease in the incidence of anemia and the number of transfusions from baseline. By cycle 2, all patients had peripheral blast clearance regardless of BM status. Patients with BM disease who did or did not achieve a complete response/clinical complete response during treatment experienced similar restoration of hematopoiesis, including peripheral blast eradication.

Conclusions

These findings demonstrate the on-target effect and unique BM-sparing profile of tagraxofusp, which are paramount when treating myelosuppressive, CD123-positive hematologic diseases. The results support single-agent tagraxofusp as standard-of-care, nonmyelosuppressive first-line treatment for BPDCN and as a potential combination partner for other CD123-positive hematologic malignancies.

Background

Teclistamab is the first approved bispecific antibody targeting B-cell maturation antigen. It has demonstrated rapid, deep, durable responses with manageable safety in patients with triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM).

Methods

The authors report results from three cohorts: Global Trial cohort consisting of 217 patients from three registrational studies (pivotal MajesTEC-1 study [n = 165], China cohort of MajesTEC-1 [n = 26], and the Japan MMY1002 study [n = 26]); the subset of 52 of 217 patients formed the Asian Trial cohort, and 42 patients treated outside of trials in the pre-approval access (PAA) program formed the Asian PAA cohort.

Results

In the Global Trial cohort, median age was 65 years, weight was 69 kg, and prior lines-of-therapy was five; 29.0% had high-risk cytogenetics and 18.9% had extramedullary disease. With 29.5 months median follow-up, overall response rate (ORR)/≥complete response (CR) was 66.4%/50.2%, median duration of response (DOR) was not reached; progression-free survival (PFS) and overall survival (OS) were 15.6, and 29.1 months, respectively. In the subset of Asian Trial cohort, baseline features were similar except for lower weight (median, 58 kg); median follow-up was 26.3 months. ORR/≥CR was 76.9%/63.5%, 24-month DOR, PFS, and OS rates were 67.5%, 59.5%, 71.4%, respectively, with medians not yet reached. Efficacy was consistent in the Asian PAA cohort with ORR/≥CR of 66.7%/40.5%. Most common adverse events were cytopenias, cytokine release syndrome, and infections. Infection management improved over time, supported by increased immunoglobulin use in later-enrolling Asian studies, aligned with guideline adoption.

Conclusion

Teclistamab demonstrated clinically meaningful benefits across diverse patients, encompassing various weight categories and geographies, reinforcing its potential as a standard of care for TCE RRMM.

Trial Registration

ClinicalTrials.gov MajesTEC-1 (NCT03145181 and NCT04557098) and Japan MMY1002 study (NCT04696809)