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2508 citation(s) found for "Yu, Yang".

Automatic Molecular Dynamics Simulation with Binding Affinity Prediction Using Deep Learning
Chen, Lingtao , Nasif, Kazi Fahim Ahmad , Deng, Bobin, Yang, Ming , Niu, Shuteng , Xie, Yixin

2025 IEEE 37th International Conference on Tools with Artificial Intelligence (ICTAI) | December 15, 2025 | Volume: No volume available | Issue: No issue available | Pages: 292-298

10.1109/ictai66417.2025.00045 Get It

Organ Preservation for Nasal Cavity Cancers Using Definitive Radiotherapy for Avoiding Rhinectomy
Yang, Fan , Gui, Chengcheng , Wu, Yingzhi, Yu, Yao , McBride, Sean M. , Shamseddine, A. , Shim, Andy, Mah, Dennis , Dunn, Lara , Michel, Loren S. , Pfister, David G. , Sherman, Eric J. , Cracchiolo, Jennifer R. , Patel, Snehal G. , Cohen, Marc A. , Lee, Nancy Y. , Mankuzhy, Nikhil P. , Boe, Lillian A. , Riaz, Nadeem , Ganly, Ian , Wong, Richard J.

JAMA Oncology | December 11, 2025 | Volume: 12 | Issue: 2 | Pages: 208

10.1001/jamaoncol.2025.5241 | PMID 41379436 Get It

This cohort study evaluates the use of definitive rhinectomy and adjuvant radiotherapy with or without chemotherapy for patients who declined rhinectomy or had unresectable disease.
Magnetic resonance elastography characterization of meningioma mechanical properties for improved neurosurgical planning and resection: a prospective cohort study
Bai, Shengjun, Zeng, Yu , Hong, Yang , Han, Shuai , Zhang, Tianhe, Guo, Mingzhe, Wu, Jianqi , Sheng, Yiyang, Wu, Anhua , Zheng, Keni, Huston Iii, John, Jiao, Niandong, Cheng, Wen , Bai, Shengjun, Zheng, Keni , Zhang, Tianhe, Guo, Mingzhe, Liu, Tianqi , Manduca, Armando , Huston, John , Wu, Qi‐Jun , Jiao, Niandong , Yin, Ziying , Shi, Yu

International Journal of Surgery | December 11, 2025 | Volume: 112 | Issue: 3 | Pages: 6859-6871

10.1097/js9.0000000000004199 | PMID 41376349 Get It

Background: Accurate characterization of tumor stiffness and adhesion is crucial when surgically resecting meningiomas. Currently, such determinations are difficult to ascertain through standard preoperative imaging diagnostics and clinical experience. Herein, we explored magnetic resonance elastography (MRE) as a means of assessing these parameters and thereby improving neurosurgical resections. Methods: This prospective study of 193 patients with meningiomas involved three distinct patient subsets (cohort 1, 88 [2017–2021]; cohort 2, 55 [2022–2023]; cohort 3, 50 [2023–2024]. We analyzed preoperatively obtained MRE data on meningioma stiffness (cohorts 1 and 2) and adhesion (cohort 2) for accuracy, while matching subjects with or without MRE studies (cohort 3, 1:1 ratio) to define the role of preoperative MRE in improving operative outcomes. Results: Areas under the curve (AUCs) for MRE in gauging meningioma stiffness and adhesion were 0.87 and 0.89, respectively. Both parameters significantly surpassed empiric predictions of stiffness and adhesion rendered by surgeons and radiologists, based on routine magnetic resonance imaging (MRI). MRE-determined stiffness measures independently correlated with prolonged resection duration, whereas MRE-assessed adhesion showed independent associations with increased blood loss, longer duration of tumor resection, and higher risk of pial injury. Ultimately, results based on cohort 3 demonstrated that MRE has great potential in this setting to improve neurosurgical procedures by significantly reducing intraoperative bleeding, resection duration, and risks of pial injury. Conclusion: MRE is a promising, noninvasive tool for accurately assessing meningioma stiffness and adhesion, standing to improve the precision and safety of needed surgical intervention.
HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer
Dièras, Véronique , Martín, Miguel , Lerebours, Florence , Tsurutani, Junji , Savard, Marie-France , Jerzak, Katarzyna J. , Hu, Xichun , Pimentel, Luciana Carla Martins de Aquino, O’Sullivan, Ciara C. , Tokunaga, Eriko , Sohn, Joohyuk , Cronemberger, Eduardo , Müller, Volkmar , Yang, Shan, Granata, G. , Shen, Qi , Santarpia, Libero, Investigators, on behalf of the HER2CLIMB-05, Curigliano, Giuseppe , Martin, Miguel , Tsurutani, Junji , Savard, Marie-France , Jerzak, Katarzyna J , Hu, Xichun , O'Sullivan, Ciara C, Tokunaga, Eriko , Okines, Alicia , Huang, Chiun-Sheng , Jacot, William , Sohn, Joohyuk , Cronemberger Silva, Eduardo , Granata, Giovanna , Hamilton, Erika P , Curigliano, Giuseppe , Pimentel, Luciana Carla Martins de Aquino, Huang, Chiun‐Sheng , Shen, Qi, Santarpia, Libero , Hamilton, Erika , Investigators, on behalf of the HER2CLIMB-05

Journal of Clinical Oncology | December 10, 2025 | Volume: 44 | Issue: 17 | Pages: 1597-1607

10.1200/jco-25-02600 | PMID 41369677 Get It

PURPOSE The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582 ) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (MBC). METHODS Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety. RESULTS Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor–positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs. CONCLUSION Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.
(271) A Case of Testicular Tetany
Lehner, K., Seyer, A, Ziegelmann, M, Yang, Daniel S. , Lehner, K, Ziegelmann, M

The Journal of Sexual Medicine | December 9, 2025 | Volume: 22 | Issue: Supplement_4 | Pages: No page available

10.1093/jsxmed/qdaf320.267 Get It

Abstract Introduction Chronic orchialgia is a common urologic complaint, and is estimated to make up 2.5 to 5% of urology clinic consultations. Hyperactive cremaster reflex is an often under-diagnosed source of chronic testicular pain, wherein patients experience vigorous muscular retraction of the testicles up to the external inguinal ring. This has been related to possible anatomic thickening of the cremaster muscles, or an attenuated external oblique aponeurosis. Objective To report a unique etiology and subsequent treatment of chronic orchialgia. Methods We present a case of an individual who developed new onset of hyperactive cremaster reflex after hamstring and rectus abdomonis tear during a sporting injury. Results Patient is a 37-year-old male who presented with new onset of bilateral testicular pain and chronic testicular retraction. 6 weeks prior to presentation, while playing soccer, he sustained a complete tear in the right hamstring, and partial tearing of the right rectus abdominis-adductor aponeurosis at the pubic symphysis. He completed conservative therapy with heat and ice, an extended course of anti- inflammatory medications, and physical therapy without relief. On exam, testicles were bilaterally high riding, and cremasteric muscles were noted to be in tonic spasm. Testicles would be brought into the scrotum, but were noted to rapidly ascend. He was offered injection of neuromodulator into the cremasteric muscles versus bilateral microsurgical cremaster release, and opted for the latter treatment. Bilateral cremasteric muscle fibers were ligated and excised from the external ring down to the testicle proper, and testicles were pexied in place. At follow-up, he reported complete resolution of pain and tonic retraction. Testicles were found to have normal anatomic lie within the dependent portion of the scrotum. Conclusions In patients with chronic testicular pain refractory to conservative measures, the cremasteric muscles may play a role in potentiating pain signaling through chronic, unprompted muscular spasm. This should especially be considered after regional musculoskeletal injuries affecting pelvic and inguinal muscle groups. In this select group of patients, excision of the cremasteric muscles to release cremasteric tension may be a viable treatment option for resolution of chronic pain. Disclosure No
(028) Changing the Status Quo: A Randomized Controlled Trial Comparing Long-Acting and Short-Active Local Anesthetics for Postoperative Pain Control After Penile Prosthesis Placement
Almohtasib, J, Anians, Wyatt, Parikh, Niki , Kohler, T, Ziegelmann, M., Almohtasib, Jamil , Kohler, Tobias S , Helo, Sevann , Yang, D

The Journal of Sexual Medicine | December 9, 2025 | Volume: 22 | Issue: Supplement_4 | Pages: No page available

10.1093/jsxmed/qdaf320.028 Get It

Abstract Introduction The opioid epidemic has encouraged increased efforts to minimize postoperative opioid use, particularly in urologic procedures. While short-acting local anesthetics are often used in inflatable penile prosthesis (IPP) placement, their effects diminish quickly, potentially leading to higher opioid requirements. Liposomal bupivacaine (LB), a long-acting local anesthetic, may reduce opioid requirements, but its cost and limited prospective data in IPP patients warrant further investigation. Objective To compare the efficacy of long-acting liposomal bupivacaine with short-acting ropivacaine in reducing postoperative pain and opioid consumption following inflatable penile prosthesis (IPP) placement. Methods This randomized controlled trial enrolled adult males undergoing primary IPP placement via a penoscrotal approach. Participants were randomized to receive either LB (20 mL Exparel + 20 mL bupivacaine 0.25%) or ropivacaine (40 mL of 0.5%) as part of a standardized multimodal analgesia protocol. All patients received acetaminophen, gabapentin, and meloxicam perioperatively, with oxycodone prescribed as needed postoperatively (figure 1). The primary outcome was postoperative opioid consumption measured in oral morphine equivalents (OME). Secondary outcomes included pain and anxiety scores assessed on postoperative days (POD) 3, 7, and 14 using visual analog scales. Results Only 13 patients completed the study due to difficulties in recruitment (9 in the long-acting group, 4 in the short-acting group). The long-acting group demonstrated consistently lower opioid consumption at all follow-up points. On POD 3, the median cumulative OME was 7.5 vs. 41.25 in the short-acting group. By POD 14, cumulative OME was 15.0 vs. 93.75. (Figure 2) Pain scores followed a similar pattern, with the long-acting group reporting lower median scores on POD 3 (4 vs. 6) and POD 7 (4 vs. 6). Anxiety scores were also lower in the long-acting group throughout the follow-up. Use of non-opioid analgesics was similar across both groups. Conclusions Despite a limited sample size, this trial showed consistent trends favoring LB over ropivacaine for reducing opioid use and pain following IPP placement. These findings suggest potential clinical benefit but require validation in larger, multicenter studies. The trial also illustrates the difficulty of conducting randomized studies when institutional practices strongly favor one approach. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo pharmaceuticals.
Number needed to treat to avoid progression or death: Zanubrutinib vs other COVALENT bruton tyrosine kinase inhibitors in Relapsed/Refractory chronic lymphocytic leukemia
Shadman, Mazyar, Brown, Jennifer R. , Xue, Mei , Massoudi, Marjan , Williams, Rhys , Yang, Keri, Shadman, Mazyar , Campbell, David Graham , Yang, Keri, Tam, Constantine S.

Blood | December 5, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 4553-4553

10.1182/blood-2025-4553 Get It

Abstract Introduction Bruton tyrosine kinase inhibitors (BTKis) have changed the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Efficacy was demonstrated for zanubrutinib and ibrutinib in high-risk R/R CLL patients in the ALPINE (NCT03734016) trial, for ibrutinib and acalabrutinib in the ELEVATE-RR (NCT02477696) trial, and for acalabrutinib in the ASCEND (NCT00135226) trial. While there is limited head-to-head comparative trial data of all covalent BTKis in the treatment of high-risk R/R CLL, a previously published network meta-analysis (NMA) used data from the ALPINE, ELEVATE-RR, and ASCEND trials, and reported that zanubrutinib demonstrated significantly improved relative efficacy compared to ibrutinib and acalabrutinib in high-risk R/R CLL (Shadman 2025). Within this NMA, high-risk R/R CLL populations were defined based on the prespecified definitions within each trial, including patients with del(17p) and/or TP53 mutations in the ALPINE and ASCEND trials, and del(17p)/del(11q) in the ELEVATE-RR trial. This study aimed to compare zanubrutinib versus ibrutinib and acalabrutinib in high-risk R/R CLL by calculating the number needed to treat (NNT) to avoid one progression or death. Methods A model was developed to evaluate the NNT among high-risk R/R CLL patients to avoid a progression or death. Progression free survival (PFS) data for zanubrutinib in high-risk patients were extracted from the ALPINE trial. PFS values for ibrutinib and acalabrutinib were derived from the previously published NMA study. PFS for ibrutinib and acalabrutinib were calculated by applying PFS hazard ratio from the NMA results to the zanubrutinib PFS value for the high-risk population in the ALPINE trial. 24-month PFS (72.6% for zanubrutinib, 52.0% for ibrutinib, and 55.9% for acalabrutinib) were used for the base case analysis of the model. Sensitivity analyses were conducted to examine the impact of alternative PFS inputs for ibrutinib, derived directly from the high-risk populations in ALPINE trial (unadjusted). Results The base case results from the NNT model indicate that for the treatment of patients with high-risk R/R CLL over 24-months, every five patients treated with zanubrutinib instead of ibrutinib results in the avoidance of one disease progression or death and every six patients treated with zanubrutinib instead of acalabrutinib results in the avoidance of one disease progression or death. Applying the model result to a hypothetical scenario of 100 patients with high-risk R/R CLL treated with zanubrutinib versus ibrutinib for two years finds approximately 20 patients will avoid disease progression events or deaths. Treating the same population with zanubrutinib versus acalabrutinib for two years will result in the avoidance of 17 disease progression events or death. Sensitivity analysis showed consistent NNT results.Conclusions The NNT analysis suggests that among high-risk R/R CLL patients, zanubrutinib is associated with more favorable clinical outcomes compared to ibrutinib and acalabrutinib. Over 24 months, zanubrutinib demonstrated a NNT of five to prevent one disease progression or death compared to ibrutinib, and an NNT of six compared to acalabrutinib, in high-risk R/R CLL patients. Study findings should be interpreted based on modeling assumptions and potential patient population differences across trials.
Outcomes of second line platinum salvage and autologous stem cell transplant compared to CD19 CAR-T in patients with Relapsed/Refractory primary mediastinal B-cell lymphoma: A multi-center, retrospective analysis
Yang, Xi , Dumke, Henry, Lanka, Sree M , Okcu, Izel, Nowakowski, Grzegorz, Doukas, Peter , Colton, Meryl D. , Pizzuti, V., Adewale, Olutobi, Baron, Kelsey, Bock, Allison M. , Karimi, Yasmin , Pizzuti, Vincenzo J. , Karimi, Yasmin H , Okcu, Izel , Pizzuti, Vincenzo J , Schroers‐Martin, Joseph G. , Sawalha, Yazeed , Nowakowski, Grzegorz, Karmali, Reem , Spinner, Michael A. , Pizzuti, Vincenzo, Kamdar, Manali , Adewale, Olutobi, Tiger, Yun Kyoung , Geer, Marcus

Blood | December 5, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 783-783

10.1182/blood-2025-783 Get It

Abstract Introduction: Primary mediastinal B-Cell lymphoma (PMBCL) is a rare form of large B-Cell lymphoma (LBCL) with around 90% of patients (pts) cured with first line (1L) treatment. For pts with relapsed or refractory (RR) PMBCL, the optimal treatment is unclear. Prior retrospective analysis in the rituximab (R) era have shown high response rates to platinum salvage and high-dose chemotherapy followed by autologous stem cell transplant (HDT/ASCT) in second line (2L) RR PMBCL (Bakos et al. ASH 2023 and Dumke et al. ASCO 2024). The pivotal phase III LBCL trials in early relapsing pts that compared CD19 chimeric antigen receptor-T cell (CAR-T) with HDT/ASCT as 2L treatment had few PMBCL pts: none on ZUMA-7 and 17 PMBCL on TRANSFORM, of whom only 8 were randomized to 2L CAR-T. This study aims to evaluate outcomes of 2L therapies for RR PMBCL, including pts treated with 2L CAR-T. Methods: We performed a multicenter retrospective study in pts with RR PMBCL treated between 2001 and 2025. Clinical and pathologic characteristics, treatment regimens, and efficacy outcomes were collected and analyzed. Results: 139 pts were included with 43% male, 69% Caucasian, 7.9% Black, 8.6% Asian and 79% Non-Hispanic. R-EPOCH (64%) and (32%) were the most common 1L treatments and all pts received R. Consolidative radiation was used in 21 pts (15%) as part of 1L therapy, 28% after RCHOP. Primary refractory disease with relapse ≤6 month (mo), or early relapse ≤12 mo, occurred in 83% (N = 115) and 93% (N = 129 pts), respectively. At relapse, median age was 34 years (yrs), 44% had advanced stage disease, 31% had bulky disease (≥ 7.5cm). CNS relapse occurred in 8.6% of pts. Overall and complete response rate (ORR and CR) to any 2L treatment was 44% and 27%, respectively. At median follow-up of 40 months (mo) from the start of 2L treatment, median PFS of the entire cohort was 3.2 mo with a 3 yr OS of 70%. For 2L treatment, N=93 (67%) pts were treated with platinum salvage with intention to proceed with HDT/ASCT. Most commonly used platinum salvage regimens were ICE± R (n= 53, 38%), R-DHAP (n=23, 17%), R-GemOx (n= 5, 3.6%), and GDP ± R (n= 10, 7.2%), and the majority (95%) of pts received R with 2L therapy. ORR and CR to platinum salvage was 46% and 15% respectively. With a median follow up of 30 mo from start of 2L therapy, median PFS was 2.6 mos, and 3 yr PFS and OS was 15% and 64%, respectively. Of the 93 pts treated with platinum salvage, only 25 pts (27%) proceeded with HDT/ASCT- of whom, N = 17 (68%) achieved a CR after ASCT. In patients that proceeded to ASCT, relapses occurred in 10 pts (40%) with a 3 yr PFS and OS 56% and 83%, respectively. CAR-T was used as 2L in 20 pts (14%)- most commonly either axi-cel (N =7) or liso-cel (N = 8). ORR and CR to CART was 89% and 55% respectively, median PFS and OS was NR after CAR-T infusion and 3 yr PFS and OS was 55% and 95%, respectively. Other 2L treatments included pembrolizumab (N =3), brentuximab vedotin (BV) + nivolumab (N= 4) or single agent BV (N=2). Radiation was given as part of 2L treatment in 25.9% of pts. 2L CAR-T therapy was associated with improved ORR (OR 7.60, 95% CI 1.68 – 34.55, p = 0.002), improved CR rate (OR 4.15, 95% CI 1.49 – 11.53, p = 0.008) and improved PFS (HR 0.18, 95% CI 0.06 – 0.57, p = 0.004) compared to pts treated with 2L platinum salvage. There was no difference in OS between pts treated with platinum salvage or 2L CAR-T. A total of 96 patients progressed on 2L therapy, and 92 pts (95.8%) received third-line (3L) treatment. Third line treatments included chemoimmunotherapy +/- HDT/ASCT (N= 23), CD19 CAR-T (N = 35), clinical trial (N=7), check point inhibitor-based regimen (N= 11), BV based regimen (N= 8), allogeneic stem cell transplant (N = 3) or other (N = 5), with 7 pts receiving radiation as part of 3L therapy. Median PFS and OS from start of 3L therapy was 6.7 mo and 6.4 mo, respectively. Conclusions: We report the largest cohort of pts with RR PMBCL treated in the rituximab era and the largest number of PMBCL pts treated with 2L CAR-T. This is the first analysis, to our knowledge, to show a statistically significant benefit in PFS, ORR and CR rate of CAR-T compared to platinum salvage followed by HDT/ASCT as 2L treatment in a study of exclusively RR PMBCL pts. Our dataset was largely (93%) compromised of pts with primary refractory or early relapsing disease and provides support for using CAR-T as 2L treatment in this high-risk subset of RR PMBCL patients.
Inotuzumab ozogamicin then blinatumomab for older adults with newly diagnosed, ph-negative, CD22-positive, B-cell acute lymphoblastic leukemia: Extended follow-up of alliance for clinical trials in oncology A041703 cohort 1 reveals durable remission and su
Wieduwilt, Matthew J. , Yin, Jun , Kour, Oudom, Teske, Rebecca, Escherich, Carolin S. , Yang, Jun , Byrd, Ken, Doucette, Kimberley , Mangan, James K. , Hall, Scott, Jamieson, Katarzyna , Dinner, Shira, Bseiso, Ali W., Giordano, Georgia, Saygin, Caner , Litzow, Mark, Stone, Richard M. , Stock, Wendy , Li, Zhenhua , Byrd, Ken, Mims, Alice S , Giordano, Georgia, Uy, Geoffrey L.

Blood | December 5, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 444-444

10.1182/blood-2025-444 Get It

Abstract Background: Older adults with newly diagnosed ALL treated with conventional chemotherapy have poor survival due to high rates of toxic death and disease relapse. The Alliance A041703 trial (NCT0373981) tested chemotherapy-free treatment with the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin (InO) followed by the anti-CD19-CD3 bifunctional T-cell engager blinatumomab (blina) without maintenance in older adults to reduce toxicity and increase efficacy of therapy for this patient (pt) population. We previously reported with 22-month (mo) median follow-up that the study met its primary endpoint with a 1-year (yr) event-free survival (EFS) of 75% (90% confidence interval [CI] 63-89% lower bound exceeding null rate of 10%; JCO 2023 41, 7006). Here we report secondary outcomes with 45-mo median follow-up: 3-yr EFS, 3-yr overall survival (OS), response, and relapse characteristics. Methods: Eligible pts were ≥60 yrs old with newly diagnosed, Ph-negative, CD22-positive (≥20% of blasts) B-cell ALL without planned allogeneic HCT (alloHCT), liver disease, or CNS involvement at enrollment. Induction IA was InO 0.8 mg/m2 day (d) 1, 0.5 mg/m2 d8, d15 IV on a 21d cycle. Pts with adequate cytoreduction (marrow blasts reduced ≥50% or marrow cellularity ≤20%) after IA went to IB if in CR/CRi (InO 0.5 mg/m2 d1, d8, d15 IV; 28d cycle) or IC if no CR/CRi (InO 0.8 mg/m2 on d1 and 0.5 mg/m2 on d8 and d15 IV; 28d cycle). Those without cytoreduction to IA started course II blina. Pts without events in IA/B/C received course II blina continuous IV (9 mcg/d x 7d then 28 mcg/d x 21d; 14d break; 28 mcg/d x28d). Pts with CR/CRi to InO received 2 more 28d cycles of blina; others received 3 more. CNS prophylaxis was methotrexate 15 mg intrathecal x 8 doses. EFS was time from therapy start to failure to achieve CR/CRh/CRi by the end of course II, progression, relapse, or death, whichever occurred first, censored at last follow up. OS was time from registration to death from any cause censored at the last known alive date. Results: The median age of the 33 treated pts was 71 yrs (range 60-84). Eight pts had prior therapy for alternate malignancy in CR for &gt;2 yrs prior to enrollment (6 multiple myeloma, 1 non-Hodgkin lymphoma, 1 breast cancer). Median CD22 expression was 92% (range 21-100%) and 49% had NCCN poor-risk genetics. Five pts underwent alloHCT in first CR/CRi and 2 pts received POMP maintenance after early discontinuation of blina (1 toxicity, 1 physician choice). The CR/CRi rate after InO was 85% (1 early death/refractory, 2 refractory, 2 undetermined due to low marrow cellularity on remission assessment marrow) with CR/CRi rate of 97% by completion of course II blina. With 45 mo median follow-up, the estimated 3-yr EFS was 48% (95% CI 33-70%) with a median EFS of 31 mo (95% CI 17.4-not reached [NR]) and no events after 31 mo. Sixteen events occurred: 12 relapses, 1early death, and 3 deaths in remission (1 encephalopathy, 1 relapse of multiple myeloma, 1 pulmonary complications after alloHCT). No isolated CNS relapse has been reported. Among relapses, 10 had immunophenotyping. Four (40%) were CD19-negative, one of which was also CD22-negative. Among CD19-negative relapses, genetics were hypodiploid (2), Pax5alt (1), and ZNF384-like (1, also CD22-negative). TP53 mutation or loss was observed in 5/12 (42%) relapses. Thirteen pts died. The estimated 3-yr OS was 59% (95% CI 44-79%) with median OS NR (95% CI 32-NR) with no deaths after 36 mo. In univariate analysis, EFS and OS were not impacted by age, gender, genetic risk (NCCN), prior therapy for alternate malignancy, or alloHCT in first remission. EFS was better with higher CD22 expression at diagnosis (≥90% vs &lt;90%, 3-yr EFS 60% vs 25%, P=0.044). EFS and OS were worse for detectable minimal residual disease (MRD) at any timepoint by ASO-PCR. Undetectable MRD after course IA (1 cycle InO induction) was associated with EFS with a 3-yr EFS of 52% vs 0% for detectable MRD (median NR vs 8 mo, hazard ratio [HR] 0.07, P=0.004) and a 3-yr OS of 100% vs 0% for detectable MRD (median NR vs 20 mo, HR 0.00, P=0.0014). Conclusions: Longer follow-up of chemotherapy-free treatment with InO and blina for older pts with newly diagnosed, Ph-negative, CD22-positive, B-cell ALL reveals durable remissions and survival. The A041703 regimen is a compelling option for first-line treatment of this pt population. Support: U10CA180821, U10CA18088; https://acknowledgments.alliancefound.org.
Management and outcomes of patients diagnosed with chronic myeloid leukemia in blast Phase: A multicenter analysis by the h jean khoury cure CML consortium
Iqbal, Umar , Vale, Colin , Smith, Kinaya, Waller, Allyson, McCormick, Benjamin J. , Zhang, Ling , Shukla, Asmita, Yang, Jay , Dailey-Hansen, Amanda, Tantravahi, Srinivas K. , Oehler, Vivian G. , Radich, Jerald P. , Nai, Nhi , Foucar, Charles , Pinilla‐Ibarz, Javier , Deininger, Michael W. , Sweet, Kendra , Jain, Akriti Gupta , Iqbal, Umar, Hunter, Anthony M. , Wei, Wei , Handa, Shivani , Mims, Alice S , Crane, Genevieve M. , Raychaudhuri, Suravi , Smith, B. Douglas , Chan, Onyee , Badar, Talha , Mukherjee, Sudipto , Atallah, Ehab , Xie, Zhuoer

Blood | December 5, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 904-904

10.1182/blood-2025-904 Get It

Abstract Introduction: Despite advent of multiple tyrosine kinase inhibitors (TKIs) and newer treatment methods for AML and ALL, the outcomes of patients (pts) with chronic myeloid leukemia in blast phase (CML-BP) remain poor. Consensus guidelines on treatment of CML-BP are scarce. A recent study from the European leukemia network blast phase registry on 240 pts reported marked heterogeneity in treatment patterns and lack of an accepted standard. Hence, we undertook this study through the H Jean Khoury Cure CML Consortium (HJKC3) to describe the treatment patterns and outcomes of pts with CML-BP in the US. Methods: This is a multi-institution, retrospective study. IRB approval was obtained at each institution and data sharing agreements were executed. All pts diagnosed with CML-BP based on modified MD Anderson Criteria (≥30% blasts in the blood or bone marrow or extramedullary (EM) disease) from 2010 to 2025 were included. Categorical variables were compared using Chi-square test. Overall survival (OS) was calculated from time of diagnosis of CML BP to death from any cause. Event free survival (EFS) was calculated from date of best response to event (death or relapse). Results: Of the 283 pts with CML-BP, 96 (33.9%) were female and 187 (66.1%) were males. At the time of diagnosis, 183 (64.6%) had CML-CP, 21 (7.4%) pts had CML-AP and 79 (27.9%) pts had de-novo CML-BP. For the 204 pts that were initially diagnosed with CML-CP or CML-AP, the median time to progression to CML-BP was 22.5 months (1-207 months). Median age at diagnosis of CML-BP was 50 years (range 16-86 years). EM disease was present in 78 (27.6%) pts (38 myeloid sarcoma, 30 central nervous system and 10 skin). Blasts were of myeloid phenotype in 168 (59.4%), lymphoid in 103 (36.4%) and mixed in 9 (3.2%) pts. The bcr-abl protein was p210 in 229 (80.9%), p190 in 8 (2.8%) and p230 in 2 (0.7%) pts. ABL kinase domain mutation was seen in 42.1% (80/190) pts, with T315I being the most common (n=32), followed by E255K (n=16). Next generation sequencing was performed in 117 pts. The most common mutations were ASXL1 (n=27), RUNX1 (n=14), BCOR (n=4), DNMT3A (n=4) and BCORL1 (n=3). Of the 283 pts, 269 underwent CML-BP directed therapy. 63 (23.4%) pts were treated with TKI monotherapy, 184 (68.4%) pts were treated with a combination of chemotherapy (chemo) and TKI and 22 (8.2%) pts were treated with chemo alone. Response rate after CML-BP directed therapy was 75.3% (n=213). Best response was return to CML-CP in 49 pts, CHR with PCyR in 18 pts, CCyR in 31 pts, MMR in 31 pts, MR4 in 18 pts, MR4.5 in 19 pts and MR5 in 47 pts. Rate of response with 2G and ponatinib was significantly better than imatinib (85.3% and 77.3% vs 63.6%; p=0.04). 149 (55.4%) pts proceeded to alloSCT. Of the 213 pts that responded, 59 (27.7%) relapsed. At a median follow-up of 47 months, the median OS for all pts was 19.7 months (95% CI: 16.3-40.2 months), with 5-year OS rate of 38% (95% CI: 32-45%). Pts with myeloid phenotype had a significantly lower OS compared to lymphoid and mixed phenotype (Median OS 14.9 vs 45.9 and 31.1 months respectively; p=0.02). OS of pts that were treated with a combination of TKI and chemo was significantly longer compared to pts treated with TKI or chemo alone (52.9 vs 16.1 or 7.5 months; p&lt;0.0001). Dasatinib (n=99; 34.9%) and ponatinib (n=97; 34.3%) were the most used TKIs followed by imatinib (n=23; 8.1%), nilotinib (n=21; 7.4%), bosutinib (n=8; 2.8%) and asciminib (n=3; 1.1%). Pts treated with ponatinib had a numerically longer OS compared to 2G-TKI and imatinib, however this was not statistically significant (40.1 vs 30.6 and 20.3 months; p=0.52). EFS for pts treated with ponatinib was significantly longer compared to 2G-TKI or imatinib (25.9 vs 17.6 and 15.9 months; p=0.03). In a landmark analysis, pts that underwent alloSCT within 6 months of diagnosis had a significantly longer OS compared to those who did not (69.3 vs 16.0 months; p=0.006). Conclusion: CML-BP continues to have poor prognosis. Treatment is heterogenous involving various combinations of TKI and chemo. In our analysis, treatment with 2G-TKI or ponatinib led to better responses. CML-BP with myeloid phenotype had worse OS. Treatment with ponatinib was associated with a numerically longer OS and significantly longer EFS compared to 2G-TKI and imatinib. In addition, treatment with chemo in combination with TKI and alloSCT led to improved OS.