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154 citation(s) found for "Wang, Michael".

Does diabetes affect outcome or reoperation rate after lumbar decompression or arthrodesis? A matched analysis of the Quality Outcomes Database data set
Mooney, James , Zeitouni, Daniel , Michalopoulos, Giorgos D. , Wang, Michael Y. , Coric, Domagoj , Chan, Andrew K. , Lu, Daniel C. , Sherrod, Brandon A. , Gottfried, Oren N., Shaffrey, Christopher I. , Than, Khoi D. , Hussain, Ibrahim , Virk, Michael S. , Glassman, Steven D. , Shaffrey, Mark E., Foley, Kevin T. , Chou, Dean , Slotkin, Jonathan R., Tumialán, Luis M. , Upadhyaya, Cheerag D., Potts, Eric A. , Fu, Kai-Ming, Haid, Regis W., Knightly, John J. , Mummaneni, Praveen V. , Bisson, Erica F. , Asher, Anthony L. , Bydon, Mohamad , Michalopoulos, Giorgos , Nathani, Karim Rizwan , Goldberg, Jacob L. , Agarwal, Nitin , Park, Paul

Mayo Clinic

Journal of Neurosurgery: Spine | December 2, 2023 | Volume: 40 | Issue: 3 | Pages: 331-342

10.3171/2023.9.spine23522 | PMID 38039534 Get It

OBJECTIVE Diabetes mellitus (DM) is a known risk factor for postsurgical and systemic complications after lumbar spinal surgery. Smaller studies have also demonstrated diminished improvements in patient-reported outcomes (PROs), with increased reoperation and readmission rates after lumbar surgery in patients with DM. The authors aimed to examine longer-term PROs in patients with DM undergoing lumbar decompression and/or arthrodesis for degenerative pathology. METHODS The Quality Outcomes Database was queried for patients undergoing elective lumbar decompression and/or arthrodesis for degenerative pathology. Patients were grouped into DM and non-DM groups and optimally matched in a 1:1 ratio on 31 baseline variables, including the number of operated levels. Outcomes of interest were readmissions and reoperations at 30 and 90 days after surgery in addition to improvements in Oswestry Disability Index, back pain, and leg pain scores and quality-adjusted life-years at 90 days after surgery. RESULTS The matched decompression cohort comprised 7836 patients (3236 [41.3] females) with a mean age of 63.5 ± 12.6 years, and the matched arthrodesis cohort comprised 7336 patients (3907 [53.3%] females) with a mean age of 64.8 ± 10.3 years. In patients undergoing lumbar decompression, no significant differences in nonroutine discharge, length of stay (LOS), readmissions, reoperations, and PROs were observed. In patients undergoing lumbar arthrodesis, nonroutine discharge (15.7% vs 13.4%, p < 0.01), LOS (3.2 ± 2.0 vs 3.0 ± 3.5 days, p < 0.01), 30-day (6.5% vs 4.4%, p < 0.01) and 90-day (9.1% vs 7.0%, p < 0.01) readmission rates, and the 90-day reoperation rate (4.3% vs 3.2%, p = 0.01) were all significantly higher in the DM group. For DM patients undergoing lumbar arthrodesis, subgroup analyses demonstrated a significantly higher risk of poor surgical outcomes with the open approach. CONCLUSIONS Patients with and without DM undergoing lumbar spinal decompression alone have comparable readmission and reoperation rates, while those undergoing arthrodesis procedures have a higher risk of poor surgical outcomes up to 90 days after surgery. Surgeons should target optimal DM control preoperatively, particularly for patients undergoing elective lumbar arthrodesis.
First Results from a Phase 1, First-in-Human Study of the Bruton's Tyrosine Kinase (BTK) Degrader Bgb-16673 in Patients (Pts) with Relapsed or Refractory (R/R) B-Cell Malignancies (BGB-16673-101)
Seymour, John F. , Stevens, Don A., Lasica, Masa , Wang, Michael , Kumar, Abhijeet , Alwan, Maan, By, Kunthel , Tariq, Bilal , Fabre, Shannon, Cheah, Chan Y. , Parrondo, Ricardo D , Thompson, Meghan C , Trotman, Judith , Ding, Wei , Chen, Xiangmei , Paik, Jason C. , Agarwal, Amit, Tam, Constantine S.

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4401-4401

10.1182/blood-2023-180109 Get It

Introduction: BTK inhibitors (BTKis) are approved for chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Disease that progresses on BTKis often has BTK mutations that lead to treatment (tx) resistance; novel BTK-targeting agents that overcome BTKi resistance are needed. BGB-16673 is a heterobifunctional small molecule that binds to BTK and E3 ligase, resulting in BTK degradation via ubiquitination. In preclinical models, BGB-16673 degraded wild-type (WT) BTK and known covalent and noncovalent BTKi-resistant mutant proteins, leading to tumor suppression. Methods: Pts with R/R CLL, WM, MCL, MZL, non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or Richter transformation (RT) were eligible for this open-label, first-in-human, phase 1 trial (BGB-16673-101; NCT05006716). Pts must have received ≥2 prior therapies (≥1 for RT) and have an ECOG performance status of 0-2 and adequate end-organ function. In the US and Australia, pts must have received a covalent BTKi (cBTKi) if approved for their disease. BGB-16673 was dosed daily by mouth in 28-day cycles. Escalation using a Bayesian optimal interval design with 6 dose levels (50-600 mg once daily) is planned. Primary objectives are to assess safety/tolerability and establish the maximum tolerated dose (MTD) and recommended phase 2 dose. Key secondary objectives are to assess pharmacokinetics, pharmacodynamics (PD), and preliminary antitumor activity. Safety was assessed according to CTCAE v5.0 (all pts) and iwCLL hematologic toxicity criteria (pts with CLL). Dose-limiting toxicities (DLTs) were assessed in the first 4 weeks. Response was assessed per Lugano criteria for all except CLL (iwCLL 2018 criteria) and WM (iwWM-6 criteria). Results: As of May 26, 2023, 26 pts (10 CLL, 4 MCL, 2 MZL, 4 WM, 4 FL, 1 DLBCL, 1 RT) were enrolled at 5 dose levels (50 mg, 4; 100 mg, 9; 200 mg, 9; 350 mg, 3; 500 mg, 1). Median age was 70.5 y (range, 25-83). Median number of prior therapies was 3.5 (range, 2-9), including cBTKis (n=21; 10 CLL, 4 WM, 4 MCL, 1 MZL, 1 RT, 1 DLBCL), BCL2 inhibitors (n=12; 9 CLL, 2 WM, 1 RT), and noncovalent BTKis (ncBTKis; n=4; 2 CLL, 1 WM, 1 FL). In CLL, del17p/ TP53 mutation (n=8) and unmutated IGHV (n=7) were frequent. Median follow-up was 3.5 mo (range, 0.2-13.9). MTD was not reached. Treatment-emergent AEs (TEAEs) were reported by 88.5% of pts (grade [gr] ≥3, 46.2%; serious, 38.5%). The most common TEAEs were contusion (30.8%; no gr ≥3), pyrexia (23.1%; no gr ≥3), neutropenia/neutrophil count decreased (23.1%; gr ≥3, 15.4%), and lipase increased (23.1%; gr ≥3, 3.8%; all transient and asymptomatic). No hypertension or atrial fibrillation was observed. One pt died from sepsis with possible disease progression. No discontinuations due to AEs occurred. Two pts had dose reductions due to TEAEs (gr 3 hematuria with urinary tract infection and recurrent urothelial carcinoma and gr 2 arthralgia). One DLT occurred in 1 pt at 200 mg (gr 3 maculopapular rash on day 27; after 5-day dose hold, assigned dose was recommenced with persistent gr 1 rash). BGB-16673 exposure increased in a dose-dependent manner. At steady state with doses ≥50 mg daily, BGB-16673 exposure exceeded the calculated half maximal degradation concentration for WT and cysteine 481-mutated BTK for the dosing interval. Preliminary PD data showed deep, sustained reductions in BTK protein levels in peripheral blood and tumor tissue, even at the lowest dose. Most CLL pts experienced lymphocytosis during the first 3 cycles of tx. Twenty of 26 pts (77%) remain on therapy (discontinuation: 4 progressive disease, 2 withdrawal). Of 18 response-evaluable pts, 12 (67%) responded (5/6 CLL, 1/3 MCL, 2/2 MZL, 3/4 WM, 1/2 FL, 0/1 DLBCL; 1 CR in MCL, all others had PR; Figure), including pts who received a cBTKi (n=10) and an ncBTKi (n=2). Responses started at the lowest dose level. All responders remain in response, the longest responder remaining on tx for 60 weeks. Conclusions: Preliminary data from this ongoing, first-in-human study of the novel BTK degrader BGB-16673 demonstrate a tolerable safety profile and clinical responses in heavily pretreated pts with B-cell malignancies, including those with BTKi-resistant disease. Substantial reductions in BTK protein levels in peripheral blood and tumor tissue were also observed, demonstrating proof-of-concept of a strong, on-target effect.
Pirtobrutinib in Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Patients with Prior cBTKi: Safety and Efficacy Including High-Risk Subgroup Analyses from the Phase 1/2 BRUIN Study
Cohen, Jonathon B. , Shah, Nirav N. , Eyre, Toby A. , Ujjani, Chaitra S. , Kim, Won Seog , Alencar, Alvaro J. , Lewis, David , Woyach, Jennifer A. , Maddocks, Kami J. , Seymour, John F. , Nagai, Hirokazu, Fakhri, Bita , Hernandez‐Ilizaliturri, Francisco J. , Kumar, Anita , Munir, Talha, Tsai, Donald E. , Balbas, Minna, Liu, Bin , Ruppert, Amy S. , Nguyen, Bastien , Wang, Michael , Fakhri, Bita , Jurczak, Wojciech , Zinzani, Pier Luigi , Cheah, Chan Y. , Koh, Youngil , Nasta, Sunita , Flinn, Ian W. , Tessoulin, Benoit , Ma, Shuo , Patel, Krish , Wang, Yucai , Rhodes, Joanna , Tam, Constantine S. , Vose, Julie M. , Hoffmann, Marc Steven , Zelenetz, Andrew D. , Roeker, Lindsey E.

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 981-981

10.1182/blood-2023-181627 Get It

Background: Despite the efficacy of covalent (c) Bruton tyrosine kinase inhibitors (BTKi) in R/R MCL, disease relapse arises through evolution of resistance mechanisms or development of cBTKi intolerance. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi has favorable oral pharmacology that enables continuous BTK inhibition throughout the daily dosing interval regardless of the intrinsic rate of BTK turnover. Pirtobrutinib is the first BTKi to demonstrate durable efficacy following prior cBTKi therapy in heavily pre-treated R/R MCL and was well-tolerated with a low frequency of treatment discontinuation due to toxicity (Wang et al., JCO, 2023). Pirtobrutinib is approved in the USA to treat relapsed or refractory MCL after at least two lines of systemic therapy including a prior cBTKi. Here, we report updated results of pirtobrutinib therapy in all patients (pts), including those with biologically high-risk R/R MCL with a median survival follow-up of 24.2 months (range, 18.2-29.8). Methods: Pts with R/R MCL received pirtobrutinib monotherapy in the multicenter Phase 1/2 BRUIN trial (NCT03740529). Efficacy was assessed in all cBTKi pre-treated pts, as well as in cBTKi treatment-naïve pts. Key endpoints included overall response rate (ORR) as assessed by independent review committee per Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Pts were included across the dose escalation range and expansion (25-300 mg/day) with 93% (n=141) receiving at least one dose of 200 mg/day, the FDA-approved dose. A data cut of 05 May 2023 was utilized. Results: Among all 152 pts with R/R MCL who received a prior cBTKi, the median age was 70 years (range, 46-88), and 52% had intermediate-risk and 28.3% had high-risk sMIPI scores. Median prior lines of therapy were 3 (range, 1-9), including an anti-CD20 antibody (96.7%), chemotherapy (90.1%), immunomodulator (17.1%), stem cell transplant (21.7%), BCL-2 inhibitor (15.8%), CAR-T cell therapy (8.6%), and PI3K inhibitor (3.9%). Among pts with high-risk biomarker data available, 30/60 (50%) had TP53 mutations and 45/63 (71%) had a Ki-67 index of ≥30%. The ORR for cBTKi pre-treated pts was 49.3% (95% CI, 41.1-57.6), including 15.8% complete responses (n=24) and 33.6% partial responses (n=51), whilst cBTKi naïve pts (n=14) had an ORR of 85.7% (95% CI, 57.2-98.2). The ORR among 128 pts who had discontinued a prior cBTKi due to PD and 21 pts who had discontinued for toxicity/other reasons was 43.0% and 90.5%, respectively. Among the 75 responding cBTKi pre-treated pts, the median DOR was 21.6 months (95% CI, 9.2-27.2) at a median follow-up of 24 months. The 18- and 24-month DOR rates were 51.9% (95% CI, 37-64.8) and 38.9% (95% CI, 22.7-54.8), respectively. ORR and DOR by high-risk subgroups (including blastoid/pleomorphic variants, Ki-67 index ≥30%, and TP53 mutations) are shown in Table 1. The 18- and 24-month DOR rates among 12 responding cBTKi naïve pts were both 90.0% (95% CI, 47.3-98.5). The median PFS and OS for cBTKi pre-treated pts was 5.6 months (95% CI, 5.3-9.2), and 23.5 months (95% CI, 17.1-NE), respectively. In the MCL cohort (n=166), the most frequent treatment-emergent adverse events (TEAEs) were fatigue (31.9%), diarrhea (22.3%), and dyspnea (17.5%). The most common Grade ≥3 TEAE was neutropenia/neutrophil count decreased (13.3%) and the rate of Grade ≥3 infections was (19.9%). Grade ≥3 hemorrhage/hematoma (2.4%) and all-grade atrial fibrillation/flutter (3.6%) were infrequent. Overall, 8 pts (5%) had treatment-related AEs leading to dose reductions and 5 (3%) had treatment-related AEs leading to pirtobrutinib discontinuation. Conclusion: Pirtobrutinib continues to demonstrate durable efficacy and a favorable safety profile in heavily pre-treated R/R MCL pts with prior cBTKi therapy. High ORRs were observed in pts who had PD on a prior cBTKi, and in pts with high-risk disease features including blastoid/pleomorphic variants, elevated Ki-67 index, and TP53 mutations.
Multicenter Study of Mantle Cell Lymphoma Outcomes Following First-Line Bendamustine-Rituximab and Second-Line Bruton's Tyrosine Kinase Inhibitor Therapy
Kumar, Anita , Joseph, Ashlee , Hill, Brian T. , Maddocks, Kami J. , Danilov, Alexey V. , McCarthy, Christine , Ruan, Jia , Nizamuddin, Imran , Khan, Nazneen B., Ouchveridze, Evguenia, Young, Philip, Portell, Craig A. , Harris, Zoey I., Pongas, Georgio, Lossos, Izidore S. , Baidoun, Firas, Gerber, Drew G. , Greenwell, Irl Brian , Stack, Anthony C., Messmer, Marcus , Narkhede, Mayur , Wang, Michael , Moyo, Tamara K. , Anna, Jacob, Stanisic, Alexander V., Kugathasan, Laveniya , Villa, Diego , Cohen, Jonathon B. , Martin, Peter , Stanisic, Alexander , Brooks, Taylor R , Portell, Craig A , Stanisic, Alexander V , Wang, Yucai , Larson, Melissa C. , Hwang, Steven R. , Brooks, Taylor , Bond, David A. , Kahl, Brad S. , Grover, Natalie S. , Ouchveridze, Evguenia, Tun, Aung M. , Muñoz, Javier , Reagan, Patrick Michael , Ryan, Christine E. , Merryman, Reid W. , Baidoun, Firas , Moustafa, Muhamad Alhaj , Ayyappan, Sabarish Ram , Link, Brian K. , Velayati, Arash , Banaszak, Lauren Gabriele , Pophali, Priyanka A. , Stack, Anthony , Mehta, Amitkumar , Jain, Preetesh , Ghosh, Nilanjan , Bhansali, Rahul S. , Barta, Stefan K , Kamdar, Manali , Karmali, Reem , Maurer, Matthew J. , Cerhan, James R.

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 300-300

10.1182/blood-2023-182942 Get It

Background: Bendamustine and rituximab (BR) is a standard-of-care first-line (1L) therapy for older or unfit patients with mantle cell lymphoma (MCL). The SHINE trial compared BR with rituximab maintenance plus ibrutinib vs placebo in patients ≥65 years old and showed that the ibrutinib arm had significantly improved progression-free survival (PFS; median 80.6 vs 52.9 months) but similar overall survival (OS; 57% vs 55% at 7 years) compared to the placebo arm. Whether sequential treatment with BR in 1L and a Bruton's tyrosine kinase inhibitor (BTKi) in second-line (2L) can result in a similar cumulative PFS compared to 1L BR plus BTKi combination therapy is unknown. To provide insight to this question, we modeled observational data to evaluate MCL outcomes after 1L BR and 2L BTKi therapy in the BTKi era. Methods: Patients with MCL who received 1L BR with or without rituximab maintenance in 2014-2020 at one of the 27 participating centers were included. Exclusion criteria included participation in the SHINE or ECHO trials, any additional 1L therapy other than BR (with or without rituximab maintenance), and stem cell transplant consolidation after 1L BR. Baseline characteristics, treatment, and follow-up data were abstracted by chart review. Event-free survival (EFS) was defined as time from index line treatment start to the first event (progression, relapse, retreatment, or death). OS was defined as time from index line treatment start to death. Using an intention-to-treat (ITT) framework, EFS2 was defined as time from 1L BR start to progression, relapse, or retreatment following 2L BTKi treatment or death. Patients who received a non-BTKi treatment at 2L were censored for EFS2 at 2L treatment start; living patients without an event following 1L BR or 2L BTKi were censored for EFS2 at last follow-up. Results: A total of 618 patients with MCL who received 1L BR in 2014-2020 were included. The median age was 71 (IQR 65-76) years, and 447 (72%) were male. 59 (11%) patients had an ECOG PS ≥2, 566 (93%) had stage III-IV disease, and simplified MIPI was low in 105 (21%), intermediate in 200 (39%), and high in 202 (40%) patients. The median follow-up following 1L BR start was 57.4 (95% CI 53.8-63.2) months. Response data were available in 580 patients, and the best ORR was 92% (79% complete response [CR] and 13% partial response [PR]). 258 (42%) patients received rituximab maintenance. As of last follow-up, 255 patients were alive and in remission after 1L BR, 92 patients died without 2L therapy, and 271 patients received a 2L therapy. The median EFS was 34.1 (95% CI 31.0-40.0) months. The median OS was 97.8 (95% CI 81.2-NA) months, the 5-year OS rate was 58.6% (95% CI 54.4-63.2), and the 7-year OS rate was 56.7% (95% CI 52.4-61.5) (Fig 1). Among the 271 patients who started a 2L treatment, 203 (75%) received a BTKi at 2L - 101 (50%) ibrutinib, 76 (37%) acalabrutinib, and 26 (13%) zanubrutinib. The median follow-up following 2L BTKi start was 38.5 (95% CI 31.3-45.1) months. Response data were available in 171 patients, and the best ORR was 64% (36% CR, 28% PR). The median EFS was 10.7 (95% CI 7.7-14.0) months, and the median OS was 24.8 (95% CI 17.3-33.1) months with 2L BTKi therapy (Fig 2). By ITT analysis, the median EFS2 following 1L BR and 2L BTKi was 72.1 (95% CI 56.7-97.8) months (Fig 1). A subset analysis of patients aged ≥65 years (n=471; 198 [42%] received rituximab maintenance) showed similar results. The median EFS with 1L BR was 32.7 (95% CI 29.1-36.3) months. The median OS was 81.5 (95% CI 65.0-NA) months, and the 7-year OS rate was 53.3% (95% CI 48.3-58.7). 208 patients received a 2L therapy, 163 (79%) with a BTKi. The median EFS was 11.5 (95% CI 7.6-15.8) months, and the median OS was 21.0 (95% CI 14.0-29.6) months with 2L BTKi therapy. By ITT analysis, the median EFS2 following 1L BR and 2L BTKi was 58.0 (95% CI 50.2-77.0) months. Conclusion: In this multicenter retrospective study, initiation of 1L BR (with or without rituximab maintenance) resulted in a 7-year OS of 57%. Median EFS2 for sequential 1L BR and 2L BTKi was 72.1 months. In context, the SHINE study reported a median PFS of 80.6 months in the BR (with rituximab maintenance) plus ibrutinib arm and a 7-year OS of 57% in the ibrutinib arm and 55% in the placebo arm, where 39% of patients received a BTKi in 2L. Within the constraints of observational data, our results provide support for sequential use of BR in 1L and BTKi in 2L for patients with MCL.
What factors influence surgical decision-making in anterior versus posterior surgery for cervical myelopathy? A QOD analysis
Park, Christine , Shaffrey, Christopher I. , Than, Khoi D. , Michalopoulos, Giorgos D. , Chan, Andrew K. , Bisson, Erica F. , Sherrod, Brandon A. , Asher, Anthony L. , Coric, Domagoj , Potts, Eric A. , Foley, Kevin T. , Wang, Michael Y. , Fu, Kai-Ming, Virk, Michael S. , Knightly, John J. , Meyer, Scott A., Upadhyaya, Cheerag D., Shaffrey, Mark E., Buchholz, Avery L., Tumialán, Luis M. , Turner, Jay D. , Chou, Dean , Chaudhry, Nauman S. , Haid, Regis W., Mummaneni, Praveen V. , Bydon, Mohamad , Gottfried, Oren N., El Sammak, Sally, Michalopoulos, Giorgos , Sammak, Sally El , Park, Paul , Agarwal, Nitin

Mayo Clinic

Journal of Neurosurgery: Spine | November 11, 2023 | Volume: 40 | Issue: 2 | Pages: 206-215

10.3171/2023.8.spine23194 | PMID 37948703 Get It

OBJECTIVE The aim of this study was to explore the preoperative patient characteristics that affect surgical decision-making when selecting an anterior or posterior operative approach in patients diagnosed with cervical spondylotic myelopathy (CSM). METHODS This was a multi-institutional, retrospective study of the prospective Quality Outcomes Database (QOD) Cervical Spondylotic Myelopathy module. Patients aged 18 years or older diagnosed with primary CSM who underwent multilevel (≥ 2-level) elective surgery were included. Demographics and baseline clinical characteristics were collected. RESULTS Of the 841 patients with CSM in the database, 492 (58.5%) underwent multilevel anterior surgery and 349 (41.5%) underwent multilevel posterior surgery. Surgeons more often performed a posterior surgical approach in older patients (mean 64.8 ± 10.6 vs 58.5 ± 11.1 years, p < 0.001) and those with a higher American Society of Anesthesiologists class (class III or IV: 52.4% vs 46.3%, p = 0.003), a higher rate of motor deficit (67.0% vs 58.7%, p = 0.014), worse myelopathy (mean modified Japanese Orthopaedic Association score 11.4 ± 3.1 vs 12.4 ± 2.6, p < 0.001), and more levels treated (4.3 ± 1.3 vs 2.4 ± 0.6, p < 0.001). On the other hand, surgeons more frequently performed an anterior surgical approach when patients were employed (47.2% vs 23.2%, p < 0.001) and had intervertebral disc herniation as an underlying pathology (30.7% vs 9.2%, p < 0.001). CONCLUSIONS The selection of approach for patients with CSM depends on patient demographics and symptomology. Posterior surgery was performed in patients who were older and had worse systemic disease, increased myelopathy, and greater levels of stenosis. Anterior surgery was more often performed in patients who were employed and had intervertebral disc herniation.
Greater improvement in Neck Disability Index scores in women after surgery for cervical myelopathy: an analysis of the Quality Outcomes Database
Patel, Arati , Umbach, Gray , Chan, Andrew K. , Le, Vivian , Bisson, Erica F. , Bydon, Mohamad , Chou, Dean , Glassman, Steve, Foley, Kevin T. , Shaffrey, Christopher I. , Potts, Eric A. , Shaffrey, Mark E., Coric, Domagoj , Knightly, John J. , Wang, Michael Y. , Fu, Kai-Ming, Slotkin, Jonathan R., Asher, Anthony L. , Virk, Michael S. , Haid, Regis W., Gottfried, Oren N., Meyer, Scott A., Upadhyaya, Cheerag D., Tumialán, Luis M. , Turner, Jay D. , Mummaneni, Praveen V. , Kondapavulur, Sravani , Park, Paul

Mayo Clinic

Neurosurgical Focus | November 1, 2023 | Volume: 55 | Issue: 5 | Pages: E7

10.3171/2023.8.focus23423 | PMID 37913530 Get It

OBJECTIVE There is a high prevalence of cervical myelopathy that requires surgery; as such, it is important to identify how different groups benefit from surgery. The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry, that includes demographic, clinical, and patient-reported outcome data to measure the safety and quality of neurosurgical procedures. In this study, the authors assessed the impact of gender on patient-reported outcomes in patients who underwent surgery for cervical myelopathy. METHODS The authors analyzed 1152 patients who underwent surgery for cervical myelopathy and were included in the QOD cervical module. Univariate comparison of baseline patient characteristics between males and females who underwent surgery for cervical spondylotic myelopathy was performed. Baseline characteristics that significantly differed between males and females were included in a multivariate generalized linear model comparing baseline and 1-year postoperative Neck Disability Index (NDI) scores. RESULTS This study included 546 females and 604 males. Females demonstrated significantly greater improvement in NDI score 1 year after surgery (p = 0.036). In addition to gender, the presence of axial neck pain and insurance status were also significantly predictive of improvement in NDI score after surgery (p = 0.0013 and p = 0.0058, respectively). CONCLUSIONS Females were more likely to benefit from surgery for cervical myelopathy compared with males. It is important to identify gender differences in postoperative outcomes after surgery in order to deliver more personalized and patient-centric care.
Outcomes of patients with blastoid and pleomorphic variant mantle cell lymphoma
Gerson, James N. , Villa, Diego , Chapani, Parv , Li, Shaoying , Medeiros, L. Jeffrey , Wang, Michael , Cohen, Jonathon B. , Churnetski, Michael C. , Hill, Brian T. , Hernandez‐Ilizaliturri, Francisco J. , Kothari, Shalin , Bast, Martin, Fenske, Timothy S. , Gari, Swapna Narayana Rao, Maddocks, Kami J. , Bachanová, Veronika , Kolla, Bhaskar , Donovan, Alexandra M., Wagner‐Johnston, Nina D. , Messmer, Marcus , Anderson, Jennifer K., Reddy, Nishitha , Glenn, Martha, Inwards, David J. , Ristow, Kay M., Rajguru, Saurabh, Evens, Andrew M. , Klein, Andreas K. , Umyarova, Elvira , Pulluri, Bhargavi , Amengual, Jennifer E. , Diefenbach, Catherine , Fisher, Richard I., Villa, Diego , Gerrie, Alina S , Chapani, Parv , Li, Shaoying , Medeiros, L Jeffrey , Wang, Michael L , Sawalha, Yazeed , Vose, Julie , Bond, David A , Kolla, Bhaskar , Lansigan, Frederick , Wagner-Johnston, Nina , Messmer, Marcus , Mehta, Amitkumar , Ristow, Kay, Karmali, Reem , Caimi, Paolo F , Evens, Andrew M , Amengual, Jennifer E , Bachanova, Veronika , Diefenbach, Catherine S , Handorf, Elizabeth A. , Gerrie, Alina S. , Sawalha, Yazeed , Vose, Julie M. , Bond, David A. , Chavez, Julio C , Shah, Bijal , Lansigan, Frederick , Burns, Timothy Francis , Mehta, Amitkumar , Kovach, Alexandra E. , Landsburg, Daniel J. , Karmali, Reem , Kaplan, Jason , Caimi, Paolo F. , Lue, Jennifer Kimberly , Barta, Stefan K

Mayo Clinic

Blood Advances | October 24, 2023 | Volume: 7 | Issue: 24 | Pages: 7393-7401

10.1182/bloodadvances.2023010757 | PMID 37874912 Get It

Abstract Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P &lt; .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P &lt; .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P &lt; .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P &lt; .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P &lt; .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival.
Three-level ACDF versus 3-level laminectomy and fusion: are there differences in outcomes? An analysis of the Quality Outcomes Database cervical spondylotic myelopathy cohort
Ambati, Vardhaan , Macki, Mohamed, Chan, Andrew K. , Michalopoulos, Giorgos D. , Le, Vivian , Jamieson, Alysha, Chou, Dean , Shaffrey, Christopher I. , Gottfried, Oren N., Bisson, Erica F. , Asher, Anthony L. , Coric, Domagoj , Potts, Eric A. , Foley, Kevin T. , Wang, Michael Y. , Fu, Kai-Ming, Virk, Michael S. , Knightly, John J. , Meyer, Scott A., Park, Paul , Upadhyaya, Cheerag D., Shaffrey, Mark E., Buchholz, Avery L., Tumialán, Luis M. , Turner, Jay D. , Sherrod, Brandon A. , Haid, Regis W., Bydon, Mohamad , Mummaneni, Praveen V. , Michalopoulos, Giorgos , Ambati, Vardhaan

Mayo Clinic

Neurosurgical Focus | September 1, 2023 | Volume: 55 | Issue: 3 | Pages: E2

10.3171/2023.6.focus23295 | PMID 37657103 Get It

OBJECTIVE The authors sought to compare 3-level anterior with posterior fusion surgical procedures for the treatment of multilevel cervical spondylotic myelopathy (CSM). METHODS The authors analyzed prospective data from the 14 highest enrolling sites of the Quality Outcomes Database CSM module. They compared 3-level anterior cervical discectomy and fusion (ACDF) and posterior cervical laminectomy and fusion (PCF) surgical procedures, excluding surgical procedures crossing the cervicothoracic junction. Rates of reaching the minimal clinically important difference (MCID) in patient-reported outcomes (PROs) were compared at 24 months postoperatively. Multivariable analyses adjusted for potential confounders elucidated in univariable analysis. RESULTS Overall, 199 patients met the inclusion criteria: 123 ACDF (61.8%) and 76 PCF (38.2%) patients. The 24-month follow-up rates were similar (ACDF 90.2% vs PCF 92.1%, p = 0.67). Preoperatively, ACDF patients were younger (60.8 ± 10.2 vs 65.0 ± 10.3 years, p < 0.01), and greater proportions were privately insured (56.1% vs 36.8%, p = 0.02), actively employed (39.8% vs 22.8%, p = 0.04), and independently ambulatory (14.6% vs 31.6%, p < 0.01). Otherwise, the cohorts had equivalent baseline modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), numeric rating scale (NRS)–arm pain, NRS–neck pain, and EQ-5D scores (p > 0.05). ACDF patients had reduced hospitalization length (1.6 vs 3.9 days, p < 0.01) and a greater proportion had nonroutine discharge (7.3% vs 22.8%, p < 0.01), but they had a higher rate of postoperative dysphagia (13.5% vs 3.5%, p = 0.049). Compared with baseline values, both groups demonstrated improvements in all outcomes at 24 months (p < 0.05). In multivariable analyses, after controlling for age, insurance payor, employment status, ambulation status, and other potential clinically relevant confounders, ACDF was associated with a greater proportion of patients with maximum satisfaction on the North American Spine Society Patient Satisfaction Index (NASS) (NASS score of 1) at 24 months (69.4% vs 53.7%, OR 2.44, 95% CI 1.17–5.09, adjusted p = 0.02). Otherwise, the cohorts shared similar 24-month outcomes in terms of reaching the MCID for mJOA, NDI, NRS–arm pain, NRS–neck pain, and EQ-5D score (adjusted p > 0.05). There were no differences in the 3-month readmission (ACDF 4.1% vs PCF 3.9%, p = 0.97) and 24-month reoperation (ACDF 13.5% vs PCF 18.6%, p = 0.36) rates. CONCLUSIONS In a cohort limited to 3-level fusion surgical procedures, ACDF was associated with reduced blood loss, shorter hospitalization length, and higher routine home discharge rates; however, PCF resulted in lower rates of postoperative dysphagia. The procedures yielded comparably significant improvements in functional status (mJOA score), neck and arm pain, neck pain–related disability, and quality of life at 3, 12, and 24 months. ACDF patients had significantly higher odds of maximum satisfaction (NASS score 1). Given comparable outcomes, patients should be counseled on each approach’s complication profile to aid in surgical decision-making.
Cervical laminoplasty versus laminectomy and posterior cervical fusion for cervical myelopathy: propensity-matched analysis of 24-month outcomes from the Quality Outcomes Database
Mummaneni, Praveen V. , Chou, Dean , Bydon, Mohamad , Bisson, Erica F. , Shaffrey, Christopher I. , Gottfried, Oren N., Asher, Anthony L. , Coric, Domagoj , Potts, Eric A. , Foley, Kevin T. , Wang, Michael Y. , Fu, Kai-Ming, Virk, Michael S. , Knightly, John J. , Meyer, Scott A., Upadhyaya, Cheerag D., Shaffrey, Mark E., Buchholz, Avery L., Tumialán, Luis M. , Turner, Jay D. , Michalopoulos, Giorgos D. , Sherrod, Brandon A. , Haid, Regis W., Chan, Andrew K. , Michalopoulos, Giorgos , Yang, Eunice, Park, Paul , Agarwal, Nitin

Mayo Clinic

Journal of Neurosurgery: Spine | August 12, 2023 | Volume: 39 | Issue: 5 | Pages: 671-681

10.3171/2023.6.spine23345 | PMID 37728378 Get It

OBJECTIVE Compared with laminectomy with posterior cervical fusion (PCF), cervical laminoplasty (CL) may result in different outcomes for those operated on for cervical spondylotic myelopathy (CSM). The aim of this study was to compare 24-month patient-reported outcomes (PROs) for laminoplasty versus PCF by using the Quality Outcomes Database (QOD) CSM data set. METHODS This was a retrospective study using an augmented data set from the prospectively collected QOD Registry Cervical Module. Patients undergoing laminoplasty or PCF for CSM were included. Using the nearest-neighbor method, the authors performed 1:1 propensity matching based on age, operated levels, and baseline modified Japanese Orthopaedic Association (mJOA) and visual analog scale (VAS) neck pain scores. The 24-month PROs, i.e., mJOA, Neck Disability Index (NDI), VAS neck pain, VAS arm pain, EQ-5D, EQ-VAS, and North American Spine Society (NASS) satisfaction scores, were compared. Only cases in the subaxial cervical region were included; those that crossed the cervicothoracic junction were excluded. RESULTS From the 1141 patients included in the QOD CSM data set who underwent anterior or posterior surgery for cervical myelopathy, 946 (82.9%) had 24 months of follow-up. Of these, 43 patients who underwent laminoplasty and 191 who underwent PCF met the inclusion criteria. After matching, the groups were similar for baseline characteristics, including operative levels (CL group: 4.0 ± 0.9 vs PCF group: 4.2 ± 1.1, p = 0.337) and baseline PROs (p > 0.05), except for a higher percentage involved in activities outside the home in the CL group (95.3% vs 81.4%, p = 0.044). The 24-month follow-up for the matched cohorts was similar (CL group: 88.4% vs PCF group: 83.7%, p = 0.534). Patients undergoing laminoplasty had significantly lower estimated blood loss (99.3 ± 91.7 mL vs 186.7 ± 142.7 mL, p = 0.003), decreased length of stay (3.0 ± 1.6 days vs 4.5 ± 3.3 days, p = 0.012), and a higher rate of routine discharge (88.4% vs 62.8%, p = 0.006). The CL cohort also demonstrated a higher rate of return to activities (47.2% vs 21.2%, p = 0.023) after 3 months. Laminoplasty was associated with a larger improvement in 24-month NDI score (−19.6 ± 18.9 vs −9.1 ± 21.9, p = 0.031). Otherwise, there were no 3- or 24-month differences in mJOA, mean NDI, VAS neck pain, VAS arm pain, EQ-5D, EQ-VAS, and distribution of NASS satisfaction scores (p > 0.05) between the cohorts. CONCLUSIONS Compared with PCF, laminoplasty was associated with decreased blood loss, decreased length of hospitalization, and higher rates of home discharge. At 3 months, laminoplasty was associated with a higher rate of return to baseline activities. At 24 months, laminoplasty was associated with greater improvements in neck disability. Otherwise, laminoplasty and PCF shared similar outcomes for functional status, pain, quality of life, and satisfaction. Laminoplasty and PCF achieved similar neck pain scores, suggesting that moderate preoperative neck pain may not necessarily be a contraindication for laminoplasty.
P1087: PIRTOBRUTINIB IN COVALENT BTK-INHIBITOR PRE-TREATED MANTLE CELL LYMPHOMA: UPDATED RESULTS AND SUBGROUP ANALYSIS FROM THE PHASE 1/2 BRUIN STUDY WITH >3 YEARS FOLLOW-UP FROM START OF ENROLLMENT
Eyre, Toby A. , Ujjani, Chaitra S. , Alencar, Alvaro J. , Lewis, David , Maddocks, Kami J. , Munir, Talha, Balbas, Minna, Tsai, Donald E. , Wang, Chunxiao , Wang, Michael , Shah, Nirav N. , Jurczak, Wojciech , Zinzani, Pier Luigi , Cheah, Chan Y. , Izutsu, Koji , Ma, Shuo , Flinn, Ian W. , Patel, Krish , Wang, Yucai , Zelenetz, Andrew D.

Mayo Clinic

HemaSphere | August 9, 2023 | Volume: 7 | Issue: S3 | Pages: e45636b5

10.1097/01.hs9.0000971244.45636.b5 Get It