tbuckley/cabot-search huggingface dataset:
Real-world analysis of HyperCVAD + TKI for untreated Ph+ ALL.
Authors: Tara Rakiewicz, Gina Keiffer, Julia Palecki, Andrew Bernstein, Lindsay Wilde, Margaret T. Kasner
Journal: Journal of Clinical Oncology (2024)

e18500 Background: Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of acute lymphoblastic leukemia (ALL) with t(9;22) (Ph+). A single-center, single-arm, phase II study published in 2017 reported excellent outcomes in adult patients (pts) treated with ponatinib + HyperCVAD alternating with high-dose methotrexate and cytarabine (HyperCVAD). Complete remission (CR) rate was 100% with 78% of pts achieving complete molecular response (CMR). 2-year (yr) event free survival (EFS) was 81% and overall survival (OS) was 80% with 9/37 pts undergoing allogeneic stem cell transplantation (SCT). This treatment's success changed standard of care for patients with Ph+ ALL; however validation of these findings is needed. Methods: We performed a real-world, retrospective analysis of adult patients with previously untreated Ph+ ALL treated with at least 1 cycle of HyperCVAD + ponatinib or an alternate TKI, at our institution between 2016 and 2023. The primary endpoint was 2-yr EFS. Kaplan-Meier method was used to estimate all time-to-event endpoints and proportions were estimated along with 95% confidence intervals. Results: 19 patients with a median age of 46 yr were analyzed. 18 pts were newly diagnosed; 1 pt had relapsed Ph+ ALL. Median follow up was 29.4 months (m). Baseline characteristics are in the table. All evaluable patients achieved a response (18/18). 1 pt died from septic shock within 4 weeks of treatment start (5.3%). All evaluable pts achieved CMR, defined as undetectable BCR/ABL1 transcript (17/17; 1 missing). Median time to CMR was 3.83 m [1.67, 9.30]. Of the 9 pts who underwent SCT, 5 (55.6%) received ponatinib and 4 (44.4%) received an alternate TKI (p=0.350). SCT was planned in 5 pts, but performed for molecular relapse (MR) in 4 pts. No pts had clinical relapse, but incidence of MR was 40.1%. 2-yr cEFS (defined as clinical relapse or death) was 89.2% [63.1%, 97.2%]. Median cEFS was greater than 32.6 m [32.6, ∞], but when defined as death or any relapse, it decreased to 18.40 m [7.27, ∞]. 2-yr OS was 89.2% [63.1%, 97.2%]. Conclusions: While 2-yr OS and EFS are similar in our cohort to published data, a surprisingly large number of patients experienced molecular relapse, which was not reported in the original trial. While our sample size was small, there was no significant difference in CR or transplant status for patients treated with Hyper CVAD + ponatinib versus alternate TKI. [Table: see text]
Dasatinib versus high-dose imatinib for chronic-phase chronic myeloid leukemia: A meta-analysis of randomized control trials.
Authors: Fabeha Zafar, Divya Shivakumar, Diptish Wankhade, Dr. Poombal, Rahul Winayak, Ghulam Mustafa Ali Malik, Shruti Sagar Mahapatra, Shasan G.C., Laraib Ashraf, Truc Huynh, Maneeth Mylavarapu, Ali Haider
Journal: Journal of Clinical Oncology (2024)

e18523 Background: Chronic Myeloid Leukemia (CML) is one of the few cancers with a unique and identifiable genetic mutation. The issue of imatinib resistance is becoming increasingly significant in patients with chronic phase chronic myeloid leukemia (CP-CML). Methods: We systematically searched Pubmed/MEDLINE, EMBASE, and Cochrane Library from inception through March 2023 to analyze the published literature of randomized control trials (RCT) regarding patients with CP-CML resistant to imatinib. The review was carried out according to the PRISMA guidelines, and the review protocol was registered at PROSPERO (CRD42023422749). The screening was done to include studies with the following criteria: 1) Randomized control trials; (2) comparisons between high-dose imatinib and dasatinib; (3) patients with imatinib-resistant CP-CML; and (4) measurements of Major Molecular Response (MMR) and Complete Cytogenetic Response (CCyR). The quality assessment of the included studies was carried out using JBI's (Joanna Briggs Institute's) RCT checklist. Risk ratios were used to compare the effects of dasatinib vs high dose imatinib with respect to outcomes on MMR and CCyR. Data was analyzed using R version 6.2.1. A p-value of &lt;0.05 was considered statistically significant. Results: We included three studies totaling 929 patients. 585 (62.9%) patients were males. There is a statistically significant improvement in MMR (RR 1.71, 95% CI 1.09 to 2.69, p=0.021, I. = 52%) and an increase in the likelihood of achieving a CCyR (RR 1.24, 95% CI 0.90 to 1.71, p=0.197, I. =74%). Conclusions: Dasatinib shows potential as a management in CP-CML patients with imatinib resistance. However, these results should be interpreted cautiously, and further validation needs to be done with high-quality, large-scale cohort studies or clinical trials to address the safety of dasatinib.
Patients with relapsed/refractory m<i>IDH1</i> AML who proceeded to transplant after olutasidenib treatment.
Authors: Stéphane De Botton, Justin M. Watts, Brian Andrew Jonas, Mwe Mwe Chao, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2024)

e18516 Background: Hematopoietic stem cell transplantation (HSCT) in post-remission AML is potentially curative and can improve survival for patients at high risk of relapse. However, achieving remission in patients with relapsed/refractory (R/R) AML is difficult, and therapies that enable previously ineligible patients to proceed to HSCT are highly desired. Olutasidenib (OLU) is FDA-approved for treatment of R/R mIDH1 AML. In the pivotal cohort of the registrational, Ph2, open-label, multicenter trial of olutasidenib, 35% of patients achieved complete remission (CR) or CR with partial hematologic recovery (CRh) with a 25.9 mos duration of response. Here we report the characteristics and outcomes of patients treated with olutasidenib who then underwent HSCT. Methods: In the Phase 2 trial, the pivotal cohort enrolled adults with R/R m IDH1 AML. OLU was administered at 150 mg BID in continuous 28-day cycles. The primary efficacy endpoint was the CR/CRh rate. Patients who achieved remission and met criteria for transplant could proceed to HSCT with discontinuation of OLU. Data cutoff: June 18, 2021. Results: 153 patients with m IDH1 R/R AML received OLU monotherapy, and 16 (11%) proceeded to HSCT. In these 16 patients, median age was 61 (40, 67), 50% were male, and median BMI was 24 (18, 38). Baseline bone marrow blast count was 24% (6% - 60%). At baseline, 15/16 (94%) had intermediate cytogenetic risk and 1 was unknown. Time since diagnosis was 8.2 mos (1.5, 116.8). 8 (50%) were refractory and 8 were relapsed (2 for &gt;12 months). Median number of prior regimens was 2 (range 1-7). All 16 had prior induction, 2 (13%) had prior HMA, 3 (19%) had prior HSCT, and 94% (15/16) had prior intensive chemotherapy (IC), 50% (n=8) of whom were IC-refractory. Response rates to OLU in the 16 patients prior to proceeding to HSCT were 75% CR/CRh (69% CR), 19% patients CRi and 6% stable disease (see Table). All 16 patients were alive at 100 days. Median survival from start of OLU treatment has not been reached. Overall survival probability was 94% (95%CI: 63, 99) at 12 months and 61% (95% CI: 32, 80) at 24 months. The safety profile of this subpopulation was consistent with the rest of the cohort. No deaths due to an adverse event occurred. Conclusions: Olutasidenib was effective in achieving remission in patients with mIDH1 R/R AML, thus enabling patients R/R to or ineligible for intensive chemotherapy at study entry to proceed to potentially curative HSCT. Clinical trial information: NCT02719574 . [Table: see text]
Venetoclax combined with hypomethylating agents for favorable risk acute myeloid leukemia: A single center experience.
Authors: Shammas Bajwa, Brian Parkin, Arlene A. Gayle, Rushang D. Patel, Shahram Mori, Philip Pancari, Francisco Andres Socola
Journal: Journal of Clinical Oncology (2024)

e18514 Background: Favorable risk acute myeloid leukemia (FR-AML) is typically treated with intensive induction chemotherapy followed by high dose consolidative cytarabine. However, a subgroup of FR-AML are not candidates for high intensity induction because of advanced age, comorbidities, or poor performance status. For these patients, hypomethylating agents (HMA) combined with venetoclax (HMA-Ven) is inferred as the standard of care based upon results of the VIALE-A trial; however, that trial enrolled only intermediate or poor risk AML. The efficacy of HMA-Ven in FR-AML is unclear. Here we present a single center experience of this regimen in FR-AML. Methods: In this retrospective single center case series, we collected data from all patients &gt;18 years old with newly diagnosed FR-AML between January 2018 to December 2022 at AdventHealth Orlando who were treated with HMA-Ven. Patient with relapsed/refractory disease or a diagnosis of acute promyelocytic leukemia were excluded. FR-AML was defined using ELN 2022 guidelines based on the results of genomic testing of the initial bone marrow aspirate. The primary endpoints were the complete remission (CR) rate and 1-year overall survival (OS). Statistical analyses were performed using the R survminer package. Results: Newly diagnosed FR-AML who received HMA-Ven were identified (n=12). The median age was 67.5 years. 3 (25%) cases had inversion of chromosome 16 and 9 (75%) had NPM1 mutations without FLT3-ITD mutations. 11 (92%) patients received decitabine and venetoclax. Patients received a median of 2.5 cycles of HMA-Ven, and all 12 patients achieved CR after one cycle of treatment. 6 (50%) patients were consolidated with intermediate-dose cytarabine (IDAC), 3 (25%) continued HMA-Ven, 2 (17%) underwent allogeneic stem cell transplant, and 1 (8%) received enasidenib. The 1-year OS was 80% (CI 0.59-1), and the median OS was not reached. 1 patient died due to chemotherapy toxicity with IDAC, and 1 patient died due to heart complications. 2 patients relapsed, 1 after IDAC and 1 after intolerance to further treatment after 6 cycles of HMA-Ven. Conclusions: Our findings suggest that HMA-Ven is an effective treatment for newly diagnosed favorable risk AML. All patients achieved CR with one cycle of treatment with most surviving more than one year. Large multicenter studies are needed to further validate these promising results.
Safety outcomes in adult patients with AML who achieved their first complete remission with GO prior to HSCT.
Authors: Nelli Bejanyan, Vincent Ho, Miguel-Angel Perales, Partow Kebriaei, Manmeet Kaur, Mei-Jie Zhang, Paul G. D'Amico, Simon Purcell, Stephanie Dorman, Erik Vandendries, Kofi Asomaning, Wael Saber
Journal: Journal of Clinical Oncology (2024)

e18504 Background: Gemtuzumab ozogamicin (GO) is approved in the US for the treatment of newly diagnosed and relapsed/refractory (R/R) CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients of 1 month and older and 2 years and older, respectively. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most adult patients with AML in first complete remission (CR1). Clinical studies have linked GO with hepatotoxicity and hepatic veno-occlusive disease (VOD); the risk of these events may be further elevated in patients receiving HSCT. This study aimed to characterize the toxicity after HSCT in adult patients with AML who were treated with GO prior to HSCT. These analyses look at outcomes in patients who were in CR1 at the time of HSCT. Methods: This non-interventional post-authorization safety study used de-identified healthcare data from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Data were collected from adult patients in the US with newly diagnosed AML treated with GO prior to proceeding with HSCT. Data collection began on 01 September 2017, data cutoff was 04 July 2023. Results: We present data of 84 patients receiving HSCT for AML in CR1 from 19 centers with a median follow-up of 23.9 months (range, 3.0-49.7). Median age was 54.2 y (range, 18.7-74.5); 55% male. Total cumulative GO dose was 1-3 mg/m2 in 15 (18%), 4-6 mg/m2 in 15 (18%), 7-9 mg/m2 in 28 (33%) and ≥10 mg/m2 in 8 (12%) patients. Measurable residual disease (MRD) was undetectable in 50% (n=42) of patients after GO and 51% (n=43) of patients at the time of HSCT. Most patients (58%; n=49) received myeloablative conditioning and 57% (n=48) received HLA matched unrelated donor HSCT. Non-fatal VOD was reported in 6 (7%) patients, most cases were mild (n=5; 83%). Cumulative incidences of transplant-related mortality (TRM) were: 6 months, 7% (95% CI, 3-14); 2 years, 15% (95% CI, 7-25). The 2-year relapse rate was 26% (95% CI, 16-36%). Kaplan-Meier probabilities of leukemia-free survival (LFS) outcomes at 1 and 2 years were, 68% (95% CI, 57-78) and 59% (95% CI, 47-71), respectively. There were 22 deaths during the study, 10 (46%) from relapse of AML, no VOD-related deaths were observed. Conclusions: The use of GO prior to allogeneic HSCT appears to be safe with low rates of posttransplant VOD observed in patients with AML in CR1. TRM and survival outcomes are similar to historically reported rates. Clinical trial information: B1767034.
Clinical validation of a mesenchymal gene expression signature for prognosis and treatment decision making in early-stage oral cavity squamous cell carcinoma.
Authors: David N. Hayes, Gregory Mayhew, Joshua M. Uronis, Jose Zevallos
Journal: Journal of Clinical Oncology (2024)

6091 Background: Treatment for human papillomavirus (HPV)-negative oral cavity squamous cell carcinoma (OCSCC) includes surgical resection of the primary tumor, usually with elective or therapeutic neck dissection with adjuvant radiation or chemotherapy and radiation based on risk stratification. While therapeutic advances have been modest at best for over a century, the addition of chemotherapy to radiation has demonstrated benefit for the highest risk patient groups, although recurrence rates remain high for advanced-stage patients. Even more concerning, some early-stage patients demonstrate life-threatening relapses in the absence of biomarker guidance. Using retrospective analysis, our group and others have identified gene expression signatures that reveal molecular subtypes (classical, atypical, basal and mesenchymal) that could identify early-stage patients most likely to recur and are likely candidates for therapy escalation, such as chemotherapy plus radiation. We hypothesize that the mesenchymal (MS) gene expression subtype is associated with worse overall survival (OS) in early-stage, node-negative OCSCC compared to non-mesenchymal subtypes. Herein we present further clinical validation of our previously described 88-gene OCSCC classifier (Mayhew et al, 2022; PMID: 36147910). Methods: As part of a prospectively designed retrospective study, residual tumor samples and paired clinical data, including n-stage and survival, were collected for patients with node-negative OCSCC (IRB# 201706088 at Washington University in St. Louis). Using the NanoString nCounter platform, RNA was isolated and counts were generated according to the manufacturer’s specifications. Gene expression data were used to assign molecular subtypes, and associations with overall survival (OS) were investigated using Kaplan-Meier plots and cox models in patients who were pathologically node negative. Results: A total of n=137 patients had node-negative OCSCC and sufficient tumor quantity to generate molecular subtype results. Consistent with our previous findings, the MS subtype was strongly associated with inferior survival in both univariate (HR = 3.24, p = 0.0019) and multivariable (HR = 3.26, p = 0.0026) analyses, confirming a potential role for gene expression-based subtyping as a biomarker for prognostication and informing clinical treatment decisions. Conclusions: These findings confirm that the MS subtype is associated with significantly worse survival in surgically resected, early-stage OCSCC which typically demonstrate favorable outcomes. Also, these findings strongly suggest value in gene expression subtyping for prognostication and treatment decision-making in OCSCC patients and warrant the further development of the 88-gene classifier as a diagnostic test for this clinically actionable patient population.
Clinical and genomic characterization of sporadic medullary thyroid carcinoma in Chinese patients.
Authors: Yang Liu, Tingwei Lu, Xiaoyan Lin
Journal: Journal of Clinical Oncology (2024)

6094 Background: Medullary thyroid carcinoma (MTC) is a C-cell-derived epithelial neuroendocrine neoplasm. MTC has a low prevalence and a relatively worse prognosis compared with differentiated thyroid carcinoma. About 75% of all MTCs are sporadic. The clinicogenomic landscape of sporadic medullary thyroid carcinoma (sMTC) in the Chinese population was rarely described. Methods: Formalin-fixed paraffin-embedded (FFPE) samples and/or tumor tissues from a total of 121 sMTC patients from 22 centers were retrospectively collected and tested using a targeted 28-gene next-generation sequencing (NGS) panel (May 2022 to November 2023). Clinicopathological data, including age, gender, histological diagnoses, site, tumor size, and status of the lymph nodes and distant metastasis were reviewed. Regression analyses were performed to examine the association between the clinicogenomic characterization and pathologic features. Results: A total of 105 out of 121 sMTC were NGS-positive. The mutant genes included RET(66.9%), RAS(20.7%), BRAF(1.6%), TSHR(0.8%). The top 5 frequent mutations were RET M918T (24.8%, 30/121), HRAS Q61R (8.3%, 10/121), RET C634R (7.4%, 9/121), RET V804M (4.1%, 5/121), HRAS Q61K (4.1%, 5/121). Of the 13 co-mutations, 12 were RET mutations or co-occurrence of RET with other genetic alterations. Besides, the higher the age, the lower the probability of lymph node metastasis (OR=0.95, p=0.005). Also, patients with common RET mutations (including M918T, C634, C630, C611, C618, C620, A883F, S891 and V804) tended to have lymph node metastases (OR=5.67, p=0.016). We observed a significant positive linear relationship (Beta=2.0) between other gene mutations (non-RET mutations and non-RAS mutations) and tumor size. However, when the tumor diameter was analyzed according to whether it was greater than 1cm, we found that clinical factors such as age, sex, and gene mutation were not related to tumor size. Moreover, we did not find any association between this cutoff value of tumor size and lymph node metastases. It indicated that sMTC clinical diagnosis and treatment may consider pathologic and genomic features, not just whether the tumor size is &gt;1cm. Conclusions: Our study first provided the molecular characteristic of Chinese patients with large-scale sMTC. Analysis revealed that common RET mutations may be potential predictors of lymph node metastases. These conclusions remain to be validated in prospective large-scale cohorts.
Survival outcomes of concurrent radiotherapy and toripalimab versus radiotherapy alone for elderly patients with postoperative head and neck squamous cell carcinoma unfit for cisplatin.
Authors: Shengjin Dou, Wen Jiang, Lulu Ye, Rongrong Li, Guopei Zhu
Journal: Journal of Clinical Oncology (2024)

6099 Background: For elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the role of postoperative concurrent chemotherapy was controversial since the intolerable toxicities and increased acute mortality, thus, radiotherapy alone was recommended. We aimed to assess if addition of toripalimab (anti-PD-1) to radiotherapy could improve treatment outcomes for this patient population. Methods: This trial was an, open-label, phase 2, randomized study.We randomly assigned (1:1) patients aged&gt;65 years, with ECOG Performance Status(PS) of 0–2, and with postoperative Stage III-IV (AJCC 8th Staging system) HNSCC unfit for cisplatin to concurrent radiotherapy (60-66Gy) and toripalimab (240mg on D0, D21 and D42)(RT+PD-1 group) or radiotherapy alone(RT group). The primary endpoint was 2-year disease free survival (DFS). It is hypothesized to detect a difference between arms of 45%-65% in 2-year DFS. Results: Between September 2020 and May 2023, 87 patients were randomly assigned (43 in RT+PD-1 group and 44 in RT group). The median age were 71.0 years (range 66-81) for the RT+PD-1 group and 72.5 years (range 67-80 years) for RT group. In the RT+PD-1 group, 35 (81.4%) patients received at least one dose of toripalimab; 38 (88.3%) patients in the RT+PD-1 group and 36 (81.8%) patients in the RT group complete the planed radiation dose. Median follow-up was 24 months in both arms. The 2-year DFS was 55.3% with RT+PD-1 and 51.2% with RT alone (p=0.866), and the 2-year OS was 63.3% with RT+PD-1 and 78.4% with RT alone(p=0.557). In RT+PD-1 group, 18(41.8%) patients were CPS≥20%; 2-year DFS was 72.2% in patients with CPS≥20%, which was 53.8% in patients with CPS&lt;20 (p=0.412). Conclusions: The primary objective of prolonging DFS with concurrent radiotherapy and toripalimab in elderly patients unfit for cisplatin with locally advanced HNSCC was not met. For patients with CPS≥20, further study still warranted to evaluate the benefit of toripalimab in this patient setting. Biomarker analysis is still ongoing. Clinical trial information: NCT04523883 .