PURPOSE Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy. PATIENTS AND METHODS Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria. RESULTS One hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF. CONCLUSION Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.
Comorbid pulmonary complications in people with sickle cell disease (pwSCD) are associated with high rates of morbidity and mortality, and poor access to care contributes to poor outcomes among this particularly high-risk pwSCD. Our purpose was to describe the population served and the resources required for hematology, pulmonary, nursing, respiratory therapy, social work, genetics, psychology, and school liaison providers to see these patients in an integrated clinic. We abstracted demographic, medication, clinical, and diagnostics data of the pwSCD seen at least once in this clinic from February 1, 2014 to December 10, 2020 from the electronic medical record and identified 145 unique pwSCD. Abnormal lung function and bronchodilator responsiveness were detected in 31% and 42% of participants respectively. Sleep abnormalities were found in over two-thirds of those screened and 65% had ≥1 previous acute chest syndrome episode. This clinic also allowed for direct provider communication and required relatively limited resources to serve a large number of severely affected pwSCD. Given the degree of abnormal respiratory variables detected and the limited resources required to implement this model, studies are warranted to evaluate whether it has the potential to improve outcomes in high-risk populations.
People with sickle cell disease (pwSCD) are at risk of developing lung conditions that complicate their sickle cell disease (SCD) but often face healthcare access barriers. An interdisciplinary SCD-pulmonary clinic was created in 2014 at Nationwide Children's Hospital (NCH) to address access barriers that may prevent optimized treatment. We hypothesize that pwSCD and pulmonary disease would have fewer hospitalizations for acute chest syndrome (ACS), asthma, and vaso-occlusive episodes (VOEs) in the two years after their initial SCD-pulmonary clinic visit compared to the two years prior. From 2014-2020,119 pwSCD were evaluated in the SCD-pulmonary clinic and followed at NCH for at least two years before and after this visit. Acute care outcomes, pulmonary function, polysomnography, echocardiogram, laboratory, and medication prescribing data were collected and analyzed using the Wilcoxon signed ranked and McNemar's tests. The median number of acute care visits for ACS (p<0.001) and asthma (p=0.006) were significantly lower during the two years after pwSCD's initial SCD-pulmonary clinic evaluation compared to the two years prior. Asthma and allergic rhinitis were more frequently diagnosed and prescriptions for hydroxyurea (p=0.005) and inhaled corticosteroids (p=0.005) were more common in the post SCD-pulmonary clinic period. The median number of prescribed systemic corticosteroids was lower in the two years following SCD-pulmonary clinic evaluation (p<0.0001). Lactate dehydrogenase and white blood cell counts also significantly decreased. Implementing a multidisciplinary SCD-pulmonary clinic is feasible and may allow improved management of pulmonary problems and lead to improvements in health and acute care utilization.
10025 Background: Encouraging responses to chemoimmunotherapy with I/T/DIN/GM-CSF have been observed in trials for patients (pts) with relapsed/refractory HR-NBL, but factors associated with response have not been identified and duration of response has not been assessed. We aimed to evaluate timing and duration of response among pts with relapsed HR-NBL treated with I/T/DIN/GM-CSF and identify factors associated with response. Methods: We performed a multicenter retrospective cohort study of pts treated with I/T/DIN/GM-CSF. Eligibility criteria included: diagnosis of relapsed HR-NBL prior to age 30; objective response [OR; complete, partial, or minor response (CR, PR, or MR) by International Neuroblastoma Response Criteria (INRC)] or stable disease (SD) after initial therapy; receipt of I/T/DIN/GM-CSF for relapse or progression outside a clinical trial from 1/1/15-6/1/20. Logistic regression was used to identify factors associated with OR. Kaplan Meier analysis was used to determine progression-free survival (PFS). Results: We enrolled 143 pts with a median age at diagnosis of 51 months. Tumors were MYCN amplified in 52 (36%) and ALK was wild type in 73/94 (78% of tumors in which ALK status was known). 79 (55%) had received prior anti-GD2 therapy. I/T/DIN/GM-CSF comprised first relapse therapy in 96 pts (67%), second relapse therapy in 23 (16%) and subsequent therapy in 24 (17%). 70 (49%) achieved OR following I/T/DIN/GM-CSF therapy [29% CR, 15% PR, 5% MR], 30 (21%) achieved SD and 43 (30%) progressed. Median cycles received was 5 (range 1-31). 121 patients (85%) had their best response upon first disease evaluation. Later disease evaluations showed improved INRC classification in 14% of pts with initial SD, 33% with MR, and 41% with PR. Median time to OR was 2 months (range 1-21). Of the 105 relapse/progression events after starting I/T/DIN/GM-CSF (73% of pts), 59 (56%) occurred during therapy. Of the 42 pts who achieved CR with I/T/DIN/GM-CSF, 5 (12%) relapsed during I/T/DIN/GM-CSF and 17 (40%) relapsed after discontinuation. I/T/DIN/GM-CSF was discontinued in 83 pts (58%) due to suboptimal response or PD, and in 19 (13%) for toxicity. Median PFS among objective responders was 15.5 months. Among those in CR, median PFS after discontinuation of I/T/DIN/GM-CSF was 11.8 months (range 0.7-70.6). Multivariable models did not identify clinical or biologic factors associated with OR. Conclusions: 49% of pts receiving I/T/DIN/GM-CSF for relapsed HR-NBL achieved OR. Among responders, median response duration was 15.5 months. Pts with SD on first disease evaluation were unlikely to achieve OR, but > 1/3 of pts with MR/PR on first evaluation ultimately achieved CR. No identifiable clinical or biologic factors were associated with OR.
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