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35 citation(s) found for "Ganguly, Siddhartha".

Long-term real-world outcomes of axicabtagene ciloleucel (axi-cel) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
Jacobson, Caron A. , Ahmed, Sairah, Lin, Yi, Perales, Miguel-Angel, Lunning, Matthew A. , Herr, Megan, Hill, Brian T., Ganguly, Siddhartha, Perez, Waleska, Feng, Zhongyu, Best, Timothy, Lee, Grace, Nikolajeva, Olga , Du, Brad, Adedokun, Babatunde, Locke, Frederick L., Siddiqi, Tanya , Ahmed, Sairah , Ghobadi, Armin , Miklos, David B. , Perales, Miguel‐Angel , Herr, Megan M. , Hill, Brian T. , Ganguly, Siddhartha , Lee, Grace, Jaglowski, Samantha , Locke, Frederick L.

Mayo Clinic

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7028-7028

10.1200/jco.2026.44.16_suppl.7028 Get It

7028 Background: Axi-cel, autologous anti-CD19 CAR T-cell therapy, showed long-term survival and curative potential in R/R LBCL (ZUMA-1; Neelapu et al. Blood . 2023). Few studies have examined long-term outcomes beyond clinical trials. Here we report long-term real-world outcomes of axi-cel in R/R LBCL using large-sample CIBMTR data. Methods: A total of 1500 adults from 79 US centers receiving commercial axi-cel after ≥2 LOT for LBCL from Oct 2017-Aug 2020 were enrolled in a post-marketing requirement study. A protocol was developed prior to the study’s implementation, reviewed by Kite and CIBMTR. This is a secondary analysis of said study. Key outcomes were progression-free survival (PFS), overall survival (OS), time to next therapy (TTNT), disease-specific mortality (competing risks were non-relapse deaths), subsequent malignancies, and non-relapse mortality (NRM). Outcomes were analyzed descriptively. Cases with missing data were excluded separately for each endpoint. Results: As of Aug 2025, 1446 patients (pts) were included in the analysis. Median age at infusion was 62.2 y (range, 19.6-90.8: 38% of pts ≥65 y); 65% were male. Five percent of pts had ECOG PS ≥2 and 16% had high-grade lymphoma. Pts had a median of 3 (range, 2-4) prior LOT, 28% had prior autologous hematopoietic cell transplantation, and 50% received bridging therapy. At 59.7 mo median follow-up, median PFS (95% CI) was 7.9 mo (6.3-10.9) and 5-y PFS was 30% (27-32). The median OS was 25.7 mo (21.6-30.2); 5-y OS was 38% (35-41). The 5-y cumulative incidence of disease-specific mortality was 51%. Among pts who were progression-free at 2, 3, 4, or 5 y post-infusion, the OS at 6 y (95% CI) was 73% (68-78), 81% (76-86), 90% (84-94), and 94% (89-97), respectively. The median duration of response (DOR) was 25.3 mo (95% CI, 20.7-32.8) and 5-y DOR was 38% (35-41). The median TTNT was 12.2 mo and 30% did not need additional LOT at 5 y. Of pts who received subsequent salvage therapy, 12 (2%) received cell therapy, 39 (7%) received hematopoietic cell transplant, and 475 (90%) received other therapy. The 1, 2, 3, 4, and 5-y cumulative incidence of relapse (95% CI) was 49% (46-51), 52% (50-55), 54% (52-57), 55% (53-58), and 56% (53-59), respectively. No new safety signals were observed. The primary causes of death (n=864; 60%) were primary disease (540; 63%), infection (111; 13%), and organ failure (57; 7%). The 5-y cumulative incidence of NRM was 16% (95% CI, 14-18). At 5 y, 11% (95% CI, 10-13) had subsequent malignancies, mostly therapy-related myeloid neoplasms (6%) and non-melanoma skin cancer (3%); none were directly attributed to axi-cel. Conclusions: This real-world study showed sustained survival at 5 y among pts with R/R LBCL treated with axi-cel after ≥2 LOT, consistent with ZUMA-1. Infection and organ failure were common causes of NRM. These results continue to support the use of axi-cel with curative intent in R/R LBCL.
Trial in progress: CAR-T (idecabtagene vicleucel) in advanced myeloma plus iberdomide or usual monitoring (The Alliance A062102 CADMIUM Study)
Tuchman, Sascha, Geyer, Susan, Nelson, Garth, Linden, Michael, Rosenberg, Aaron, Conlin, Alison, Ganguly, Siddhartha, Harichand-Herdt, Seema, Fanning, Suzanne, Carlisle, Destin, Banerjee, Rahul, Afrough, Aimaz, Mitsiades, Constantine, Hillengass, Jens, Suman, Vera Jean, Kennedy, C., Holstein, Sarah, Dinner, Shira, Voorhees, Peter, Usmani, Saad, Tuchman, Sascha, Geyer, Susan, Nelson, Garth, Linden, Michael, Rosenberg, Aaron, Conlin, Alison, Ganguly, Siddhartha, Harichand-Herdt, Seema, Fanning, Suzanne, Carlisle, Destin, Banerjee, Rahul, Afrough, Aimaz, Mitsiades, Constantine, Hillengass, Jens, Suman, Vera Jean, Kennedy, C., Holstein, Sarah, Dinner, Shira, Voorhees, Peter, Usmani, Saad

Mayo Clinic

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 2289-2289

10.1182/blood-2025-2289 Get It

Abstract Background: Multiple myeloma (MM) remains incurable, though key advances such as chimeric antigen receptor T-cells (CAR-T) and immunomodulatory agents, now evolving toward cereblon E3 ligase modulatory drugs (CELMoDs), have substantially improved the longevity and quality of life for patients (pts). Idecabtagene vicleucel (ide-cel) is a CAR-T targeting B-cell maturation antigen (BCMA), now US FDA-approved for pts who have received ≥2 prior lines of therapy including a proteasome inhibitor, immunomodulatory agent, and CD38 monoclonal antibody. Ide-cel was initially FDA-approved for ≥4 prior lines of therapy based on the KarMMa-1 study, which demonstrated a median progression-free survival (PFS) of 8.8 months across all cell doses and median overall survival (OS) of 19.4 months (Munshi et al., New Eng J Med 2021). Although promising, the fact that virtually all pts relapse post-ide-cel indicates that further progress is needed. To that end, iberdomide is an investigational CELMoD that in combination with dexamethasone has demonstrated a 30% response rate in early phase studies of triple class-refractory MM (Lonial et al., Lancet Haem 2022). Additionally, in laboratory-based correlative studies, iberdomide, at doses of ≤1 mg (well below the recommended phase 2 dose of 1.6 mg) was shown to augment immune function, including enhanced T-cell activation and cytotoxicity, and modulation of the cytokine milieu (Amatangelo et al., Cell Rep Med 2024). Iberdomide's combined properties of direct MM cytotoxicity and T-cell potentiation have clear, potential relevance to CAR-T clinically, providing the conceptual basis for the CADMIUM study (NCT06179888), exploring the effects of iberdomide as post-ide-cel maintenance therapy in MM. Study Design and Methods: This is a randomized phase II trial with a safety run-in to evaluate if treatment with iberdomide maintenance post-ide-cel can significantly improve PFS vs. standard of care (SOC) observation without therapy, in pts with relapsed/refractory MM with ≥4 prior lines of therapy, who have received ide-cel within 3 months of registration, and no evidence of MM progression or additional MM therapy since ide-cel. Pre-ide-cel iberdomide exposure is permissible but refractoriness is not. The safety run-in will confirm tolerability of the iberdomide dose to be carried forward, where doses to be tested include: iberdomide 1 mg orally on days 1-21 of a 28-day cycle (dose level 1; DL1) and iberdomide 0.7 mg on days 1-21 of a 28-day cycle (DL2). Dose-limiting toxicities (DLTs) include any of the following during the DLT period of a pt's first three months on iberdomide: prolonged Grade 3 non-hematologic toxicities, Grade 4 non-hematologic toxicities, prolonged Grade 4 neutropenia or thrombocytopenia, or any adverse event requiring iberdomide interruption for >4 weeks. Six pts will be enrolled onto DL1; if at most 1 of these pts has a DLT, DL1 will be carried forward to the randomized part of the study. Otherwise, 6 pts will be enrolled onto DL2. The randomized part of the trial will randomize 60 pts 1:1 to either iberdomide or SOC observation without therapy. A 1-sided log-rank test with α=0.15 has 81% power to detect a true hazard ratio (iberdomide/SOC) of 0.55 or less, corresponding to an improvement in median PFS to 16 vs. 8.8 months with SOC. One interim analysis for futility is planned. Secondary outcomes include OS, best response by International Myeloma Working Group (IMWG) criteria, and deepening of response, particularly conversion to complete response with a bone marrow minimal disease-negative state by Adaptive clonoSEQ (sensitivity 1e-6). Robust correlative studies will include CAR-T persistence, assays of T- and other immune cell function, and pathological analyses of whether BCMA expression on MM cells (prior to enrollment or at relapse) or other markers predict clinical outcomes. Study status: To date, 12 pts have been screened, with 7 pts enrolled on study as part of the safety run-in (1 patient replaced). Enrollment data will be updated at presentation. Notably, an amendment is forthcoming which will enhance correlative studies and broaden eligibility criteria to include patients who have received ≥2 prior lines of therapy, conforming with ide-cel's current FDA label. Study COI: BMS is supporting correlative studies. Study Support: U10CA180821, U10CA180882; BMS; U10CA180868 (NRG Oncology); http://acknowledgements.alliancefound.org
New comorbidity index associated with survival after chimeric antigen receptor T-cell therapy for large B-cell lymphoma
Greenbaum, Uri , Hashmi, Hamza , Elsawy, Mahmoud , Kim, Soyoung , Moskop, Amy , Oloyede, Temitope, Awan, Farrukh T. , Bachanová, Veronika , Badar, Talha , Bar, Merav , Barba, Pere , Cashen, Amanda F. , Ganguly, Siddhartha , Kittai, Adam S. , Lulla, Premal , Mead, Elena, Geethakumari, Praveen Ramakrishnan , Saber, Wael , Strouse, Christopher , Valluripalli, Anusha, Wudhikarn, Kitsada , Pasquini, Marcelo C. , Dholaria, Bhagirathbhai R , Farooq, Umar , Hematti, Peiman , Hill, LaQuisa C , Jain, Michael D , Jain, Tania , Lulla, Premal D , McGuirk, Joseph , Mussetti, Alberto , Nishihori, Taiga , Olson, Amanda L , Perales, Miguel-Angel , Riedell, Peter A , Shouval, Roni , Magalhaes-Silverman, Margarida , Pasquini, Marcelo , Ahmed, Sairah , Sorror, Mohamed , Bachanova, Veronika , Badar, Talha , Strouse, Christopher S , Awan, Farrukh T , Kim, Soyoung , Moskop, Amy , Beitinjaneh, Amer , Dholaria, Bhagirathbhai , Foglesong, Jessica , Hematti, Peiman , Hill, LaQuisa C. , Jain, Michael D. , Jain, Tania , Kebriaei, Partow , Locke, Frederick L. , McGuirk, Joseph P. , Mussetti, Alberto , Nishihori, Taiga , Pennisi, Martina , Perales, Miguel‐Angel , Riedell, Peter A. , Shpall, Elizabeth J. , Magalhaes‐Silverman, Margarida , Turtle, Cameron J. , Vallurupalli, Anusha , Ahmed, Sairah , Sorror, Mohamed L.

Mayo Clinic

Blood Advances | August 14, 2025 | Volume: 10 | Issue: 1 | Pages: 217-227

10.1182/bloodadvances.2024015599 | PMID 40811818 Get It

Abstract The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T-cell (CAR-T) therapy is not well established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017 to 2020 were selected from the Center for International Blood and Marrow Transplant Research registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91 years). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37 [95% confidence interval [CI], 1.16-1.62; P< .001]; CT-CI 2: HR, 1.49 [95% CI, 1.17-1.89; P = .001]; CT-CI ≥ 3: HR, 2.55 [95% CI, 1.90-3.42; P< .001]). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T–related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.
Infection after CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma: real-world analysis from CIBMTR
Wudhikarn, Kitsada , Chen, Min , Baird, John H. , Gowda, Lohith , Rangarajan, Hemalatha G. , Abid, Muhammad Bilal , Kharfan‐Dabaja, Mohamed A. , Ganguly, Siddhartha , Young, Jo‐Anne H. , Sharma, Akshay , Modi, Dipenkumar , Salem, Baheyeldin , Vergidis, Paschalis , Smith, Melody , Boghdadly, Zeinab El , Dandoy, Christopher E. , Huppler, Anna R. , Chemaly, Roy F. , Hill, Joshua A. , Riches, Marcie , Herr, Megan M. , Martens, Michael J , Baird, John , Rangarajan, Hemalatha G , Abid, Muhammad Bilal , Kharfan-Dabaja, Mohamed A , Young, Jo-Anne H , Sharma, Akshay , Fatobene, Giancarlo , Jain, Tania , Modi, Dipenkumar , Grover, Natalie S , Salem, Baheyeldin , Batista, Marjorie Vieira , Vergidis, Paschalis , Yin, Dwight E , Kelkar, Amar H , Nishihori, Taiga , Holter Chakrabarty, Jennifer , Gergis, Usama , Smith, Melody , Dandoy, Christopher E , Murthy, Hemant S , Huppler, Anna R , Perales, Miguel-Angel , Chemaly, Roy F , Hill, Joshua A , Auletta, Jeffery J , Martens, Michael J. , Williams, Kirsten M. , Jain, Tania , Kanakry, Christopher G. , Grover, Natalie S. , Beitinjaneh, Amer , Nishihori, Taiga , Holter‐Chakrabarty, Jennifer , Murthy, Hemant S. , Perales, Miguel‐Angel , Auletta, Jeffery J.

Mayo Clinic

Blood Advances | May 28, 2025 | Volume: 9 | Issue: 21 | Pages: 5460-5472

10.1182/bloodadvances.2025016141 | PMID 40435511 Get It

Abstract Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell–associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.
Donor types and outcomes of transplantation in myelofibrosis: a CIBMTR study
Jain, Tania , Estrada‐Merly, Noel, Salas, María Queralt , Kim, Soyoung , DeVos, Jakob D. , Chen, Min , Fang, Xi , Kumar, Rajat , Elmariah, Hany , Aljurf, Mahmoud , Badar, Talha , Ballen, Karen K. , Bredeson, Christopher , DeFilipp, Zachariah , Farhadfar, Nosha , Farhan, Shatha , Gandhi, Arpita , Ganguly, Siddhartha , Hamilton, Betty K. , Inamoto, Yoshihiro , Jamy, Omer , Kharfan‐Dabaja, Mohamed A. , Krem, Maxwell M. , Lad, Deepesh , Malone, Adriana K. , Pawarode, Attaphol , Poel, Marjolein van der , Rizzieri, David A. , Savoie, Mary Lynn , Seo, Sachiko , Solh, Melhem , Üstün, Celalettin , Verdonck, Leo F. , Wirk, Baldeep , Bejanyan, Nelli , Jones, Richard J., Nakamura, Ryotaro , Scott, Bart L. , Saber, Wael , Gupta, Vikas , Salas, M Queralt , Elmariah, Hany , Bacher, Ulrike , Badar, Talha , Bhatt, Vijaya Raj , DeFilipp, Zachariah , Dholaria, Bhagirathbhai R , Farhan, Shatha , Hamad, Nada , Hamilton, Betty K , Inamoto, Yoshihiro , Jamy, Omer , Juckett, Mark , Kharfan-Dabaja, Mohamed A , Krem, Maxwell M , Al Malki, Monzr M , Malone, Adriana K , Murthy, Hemant S , Patel, Sagar , Perales, Miguel-Angel , Ringden, Olov , Rovó, Alicia , Savani, Bipin N , Savoie, Mary Lynn , Seo, Sachiko , Ustun, Celalettin , Verdonck, Leo F , Bejanyan, Nelli , Nishihori, Taiga , Nakamura, Ryotaro , Scott, Bart , Gupta, Vikas , Jain, Tania , Kim, Soyoung , Andrade‐Campos, Marcio , Agrawal, Vaibhav , Badawy, Sherif M. , Beitinjaneh, Amer , Bhatt, Vijaya Raj , Dholaria, Bhagirathbhai , Gergis, Usama , Grunwald, Michael R. , Hamad, Nada , Iqbal, Madiha , Liesveld, Jane L. , Malki, Monzr M. Al , Murthy, Hemant S. , Ortí, Guillermo, Patel, Sagar S. , Perales, Miguel‐Angel , Ringdén, Olle , Savani, Bipin N. , Wingard, John R. , Nishihori, Taiga , Oran, Betül

Mayo Clinic

Blood Advances | June 25, 2024 | Volume: 8 | Issue: 16 | Pages: 4281-4293

10.1182/bloodadvances.2024013451 | PMID 38916866 Get It

Abstract We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)–HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P < .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.
Predictors of Cytokine Release Syndrome and Neurotoxicity in Patients with Large B-Cell Lymphoma and Their Impact on Survival
Strouse, Christopher , Oloyede, Temitope, Barba, Pere , Cashen, Amanda F. , Elsawy, Mahmoud , Ganguly, Siddhartha , Geethakumari, Praveen Ramakrishnan , Greenbaum, Uri , Hashmi, Hamza , Kittai, Adam S. , Lulla, Premal , Mead, Elena, Saber, Wael , Pasquini, Marcelo C. , Strouse, Christopher S , Shouval, Roni , Kim, Soyoung , Ahmed, Sairah , Awan, Farrukh T. , Bachanová, Veronika , Badar, Talha , Beitinjaneh, Amer , Dholaria, Bhagirathbhai , Hill, LaQuisa C. , Jain, Michael D. , Jain, Tania , Kebriaei, Partow , Locke, Frederick L. , McGuirk, Joseph P. , Mussetti, Alberto , Nishihori, Taiga , Olson, Amanda L , Pennisi, Martina , Perales, Miguel‐Angel , Riedell, Peter A. , Mirza, Abu‐Sayeef , Magalhaes‐Silverman, Margarida , Shpall, Elizabeth J. , Sorror, Mohamed L. , Wudhikarn, Kitsada , Turtle, Cameron J. , Moskop, Amy

Mayo Clinic

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 355-355

10.1182/blood-2023-181181 Get It

Background: Autologous CAR-T therapy targeting CD19 is an effective treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, morbidity and mortality related to CAR-T toxicity remain significant concerns. This study aims to evaluate the patterns, risk factors, and implications of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) following CD19-CAR-T therapy in LBCL. Methods: This retrospective analysis includes 1916 LBCL patients treated with CD19-CAR-T cell therapy (axicabtagene-ciloleucel [axi-cel] 75% and tisagenlecleucel 25%) between 2018 and 2020 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Patient demographics, baseline characteristics, treatment-related variables, and clinical outcomes were collected. The incidence, severity and timing of onset of CRS and ICANS (according to median time to onset) were analyzed, factors associated with these outcomes and their impact on overall survival as time dependent covariates were done using Cox Regression multivariate analyses. Results: The median age of the patients was 64 years, with a majority having a Karnofsky performance status (KPS) below 90% (61%) and not receiving bridging therapy (67%). CRS was observed in 75.1% of patients, with 9% experiencing severe CRS (grades ≥ 3). Similarly, 43% of patients experienced ICANS, with 20% having severe ICANS (grade ≥ 3). The median time to toxicity was shorter for CRS (4 days) compared to ICANS (7 days). Nearly all the patients who developed ICANS also experienced CRS (98%; ), and the correlation between these two events and respective severities are shown in the Figure 1a. In the multivariate analyses, factors associated with development of CRS were gender (women, Odds ratio [OR] 1.39, 95% confidence interval [CI] 1.10- 1.76, p=0.006), high LDH at time of infusion (OR 1.56; 95% CI 1.22 - 2.00, p=0.002) and product (axi-cel OR 4.60, 95% CI 3.56 -5.81, p<0.001). Factors associated with the development of ICANS included age (> 65 years, OR 1.83; 1.50-2.24, p<0.001), KPS (<80%, OR 2.48; 1.88-3.27, p<0.001), disease status at infusion (treatment resistant disease, OR 1.98; 1.09-3.58, p=0.024; and untreated relapse OR 2.62, 1.35-5.10, p=0.004) and product (axi-cel, OR 5.85; 4.47-7.64, p<0.0001). Factors associated with severe and early onset CRS and ICANS are listed in the table below. The median follow-up of 14.2 months, the estimated 12-month overall survival, progression-free survival (PFS), and treatment-related mortality were 61.6% (95% CI: 59.4-63.9), 42.2% (39.9-44.5), and 4.3% (3.4-5.3), respectively. Overall CRS, early onset CRS and overall ICANS were not associated with higher mortality, however grade >3 CRS (HR 1.79; 1.41-2.28, p<0.001), grade >3 ICANS (hazard ratio [HR] 1.34; 95% CI 1.13-1.59, p=0.002) and early onset ICANS (<7 days, HR 1.23; 1.05-1.44, p=0.01) were associated with higher mortality. The impact of severe CRS on survival are shown in the landmark analysis at 30 days from infusion in the figure 1B. Conclusion: In the largest analysis of CD19-CAR-T cell therapy toxicities to date, we observed a high burden of CRS and ICANS among LBCL patients. The CAR T cell product type was consistently associated with higher incidence, shorter onset and higher severity of both toxicities. High LDH, older age and low performance score also influence the severity and onset of these outcomes. Additionally, patients who developed higher grades of CRS/ICANS and earlier onset ICANS had a higher mortality, stressing the need to develop novel strategies to mitigate the incidence and optimize management of these patients to improve their outcomes.
Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis
Murthy, Hemant S. , Zhang, Mei‐Jie , Chen, Karen , Ahmed, Sairah , Ganguly, Siddhartha , Kansagra, Ankit , Michelis, Fotios V. , Nishihori, Taiga , Patnaik, Mrinal M. , Aljurf, Mahmoud , Arai, Yasuyuki , Badar, Talha , Ballen, Karen K. , Bejanyan, Nelli , Brown, Valerie I. , Martino, Rodrigo , Cahn, Jean‐Yves , Castillo, Paul , Černý, Jan , Copelan, Edward A. , Daly, Andrew , Freytes, César O. , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Jamy, Omer , Joseph, Jacinth , Kanakry, Christopher G. , Khera, Nandita , Krem, Maxwell M. , Kuwatsuka, Yachiyo , Lekakis, Lazaros J. , Liu, Hongtao , Modi, Dipenkumar , Munshi, Pashna N. , Palmisiano, Neil , Rizzieri, David A. , Seo, Sachiko , Sharma, Akshay , Sohl, Melhm, Solomon, Scott R. , Ulrickson, Matthew L. , Üstün, Celalettin , Poel, Marjolein van der , Verdonck, Leo F. , Wagner, John L. , Wang, Trent , Wirk, Baldeep , Zeidan, Amer M. , Litzow, Mark R. , Weisdorf, Daniel J. , Saber, Wael , Kharfan‐Dabaja, Mohamed A. , Kansagra, Ankit , Michelis, Fotios V , Nishihori, Taiga , Patnaik, Mrinal , Arai, Yasuyuki , Badar, Talha , Bejanyan, Nelli , Bhatt, Vijaya Raj , Chhabra, Saurabh , Dholaria, Bhagirathbhai R , Diaz Perez, Miguel Angel , Freytes, Cesar O , Hashmi, Shahrukh K , Jamy, Omer , Krem, Maxwell M , Lazarus, Hillard M , Liu, Hongtao , Modi, Dipenkumar , Mussetti, Alberto , Patel, Sagar , Shah, Mithun V , Sharma, Akshay , Ustun, Celalettin , Wagner, John , Litzow, Mark R. , Hourigan, Christopher S , Weisdorf, Dan , Kharfan-Dabaja, Mohamed A , Murthy, Hemant S , Martino, Rodrigo , Ahmed, Sairah , Zeidan, Amer M , Deotare, Uday , Abid, Muhammad Bilal , Bacher, Ulrike , Badawy, Sherif M. , Battiwalla, Minoo , Beitinjaneh, Amer , Bhatt, Vijaya Raj , Chhabra, Saurabh , Dholaria, Bhagirathbhai , Díaz, Miguel Ángel , Grunwald, Michael R. , Lazarus, Hillard M. , Mussetti, Alberto , Patel, Sagar S. , Shah, Meera , Kebriaei, Partow , Hourigan, Christopher S.

Mayo Clinic

Blood Advances | October 4, 2023 | Volume: 7 | Issue: 22 | Pages: 7007-7016

10.1182/bloodadvances.2023011308 | PMID 37792849 Get It

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.
A simple prognostic system in patients with myelofibrosis undergoing allogeneic stem cell transplantation: a CIBMTR/EBMT analysis
Tamari, Roni , McLornan, Donal P. , Ahn, Kwang Woo , Estrada‐Merly, Noel, Hernández‐Boluda, Juan Carlos , Giralt, Sergio , Palmer, Jeanne , DeFilipp, Zachariah , Marks, David I. , Poel, Marjolein van der , Verdonck, Leo F. , Gupta, Vikas , Ali, Haris , Litzow, Mark R. , Bashey, Asad, Hashmi, Shahrukh K. , Bredeson, Christopher , Rizzieri, David A. , Abid, Muhammad Bilal , Ganguly, Siddhartha , Wirk, Baldeep , Aljurf, Mahmoud , Kindwall‐Keller, Tamila L. , Kharfan‐Dabaja, Mohamed A. , Hildebrandt, Gerhard , Pawarode, Attaphol , Solh, Melhem , Nathan, Sunita , Seo, Sachiko , Scott, Bart L. , Nakamura, Ryotaro , Yakoub‐Agha, Ibrahim , Saber, Wael , DeFilipp, Zachariah , Gupta, Vikas , Ali, Haris , Litzow, Mark R. , Hashmi, Shahrukh K , Pu, Jeffrey J , Bacher, Ulrike , Jain, Tania , Cutler, Corey S. , Kharfan-Dabaja, Mohamed A , Yared, Jean A , Nishihori, Taiga , Seo, Sachiko , Scott, Bart , Nakamura, Ryotaro , Czerw, Tomasz , Yakoub-Agha, Ibrahim , Hernández-Boluda, Juan Carlos , McLornan, Donal , Abid, Muhammad Bilal , Giralt, Sergio , Gale, Robert Peter , Battiwalla, Minoo , Díaz, Miguel Ángel , Lazarus, Hillard M. , Gergis, Usama , Liesveld, Jane L. , Beitinjaneh, Amer , Savani, Bipin N. , Agrawal, Vaibhav , Jain, Tania , Yared, Jean A. , Grunwald, Michael R. , Nishihori, Taiga , Oran, Betül

Mayo Clinic

Blood Advances | May 3, 2023 | Volume: 7 | Issue: 15 | Pages: 3993-4002

10.1182/bloodadvances.2023009886 | PMID 37134306 Get It

AbstractTo develop a prognostic model for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for myelofibrosis (MF), we examined the data of 623 patients undergoing allo-HCT between 2000 and 2016 in the United States (the Center for International Blood and Marrow Transplant Research [CIBMTR] cohort). A Cox multivariable model was used to identify factors prognostic of mortality. A weighted score using these factors was assigned to patients who received transplantation in Europe (the European Bone Marrow Transplant [EBMT] cohort; n = 623). Patient age >50 years (hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.98-1.96), and HLA-matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with an increased hazard of death and were assigned 1 point. Hemoglobin levels <100 g/L at time of transplantation (HR, 1.63; 95% CI, 1.2-2.19) and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25-2.52) were assigned 2 points. The 3-year overall survival (OS) in patients with a low (1-2 points), intermediate (3-4 points), and high score (5 points) were 69% (95% CI, 61-76), 51% (95% CI, 46-56.4), and 34% (95% CI, 21-49), respectively (P < .001). Increasing score was predictive of increased transplant-related mortality (TRM; P = .0017) but not of relapse (P = .12). The derived score was predictive of OS (P < .001) and TRM (P = .002) but not of relapse (P = .17) in the EBMT cohort as well. The proposed system was prognostic of survival in 2 large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with MF about the transplantation outcomes.
Real-World Outcomes of Axicabtagene Ciloleucel (Axi-cel) for the Treatment of Large B-Cell Lymphoma (LBCL): Impact of Age and Specific Organ Dysfunction
Jacobson, Caron A. , Dong, Hua, Hu, Zhen‐Huan , Lunning, Matthew A. , Hill, Brian T. , Ganguly, Siddhartha , Nikiforow, Sarah , Xu, Hairong , Pasquini, Marcelo C. , Locke, Frederick L. , Ma, Long, Siddiqi, Tanya , Ahmed, Sairah , Ghobadi, Armin , Miklos, David B. , Lin, Yi , Perales, Miguel‐Angel , Herr, Megan M. , Mirza, Abu‐Sayeef

Mayo Clinic

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 530-530

10.1182/blood-2021-149679 Get It

Abstract Background and Rationale: Axi-cel is a standard-of-care treatment for relapsed or refractory LBCL after 2 or more lines of systemic therapy. Some patients who would have been ineligible for ZUMA-1 criteria due to comorbidities have been treated with axi-cel in the real-world setting. We interrogated a large registry of patients treated with standard-of-care axi-cel for a definitive report on the impact of age or certain comorbidities on safety and efficacy outcomes after axi-cel infusion. Methods: From October 2017 to August 2020, 1500 patients were enrolled in the postapproval safety observational study of axi-cel treated at 79 centers. Patients eligible for the protocol and followed up for at least 6 months with complete data entry by the time of analyses were included. One patient rescinded consent and 1 was deemed ineligible. Patients previously treated with immune effector cell therapy (n=31), with incomplete follow-up reporting (n=92), or alive but last contacted <180 days postinfusion (n=32) were excluded from analysis. Main efficacy outcomes included complete and objective response rates (CR and ORR), duration of response (DOR), progression-free and overall survival (PFS and OS). Safety endpoints of interest included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Outcomes were assessed and compared by age and preselected coexisting disease or organ impairment within 3 months prior to the infusion included in the hematopoietic cell transplantation comorbidity index. Multivariate logistic and Cox regression models were used to assess the impact of age or coexistent organ dysfunction on outcomes via odds ratio (OR) or hazard ratio (HR) and their 95% CIs. Results A total of 1343 patients were included in the analysis with a median 25.1 months (range, 10.3-42.7 months) for potential follow-up, defined from infusion to data cutoff date, and a median 11.8 months (range, 0.1-38.8 months) for actual follow-up time, defined from infusion to date of death or last contact. Of these, 38% were 65 years or older (median 62 years), 4% had a performance score ≥2, 13% had cardiac comorbidities, 16% had a prior cancer, 9% were obese, 2% had moderate to severe hepatic comorbidities, and 2% had renal comorbidities. Transformed lymphoma, double or triple-hit by fluorescence in situ hybridization, prior autologous transplant and refractory disease were present in 28%, 15%, 27% and 66%, respectively. Bridging therapy was administered in 21% of patients. Overall, ORR was 74%, (CR 56%), and probabilities of DOR, PFS, and OS at 18 months were 61% (95% CI, 57-65%), 42% (95% CI, 39-45%) and 52% (95% CI, 49-55%), respectively. Overall rates of CRS and ICANS were 83% and 55%, respectively. ORR was 78% (CR 62%, median OS 17.5 [95% CI, 16.0-not evaluated (NE)] months) for patients ≥65 years, ORR 57% (CR 29%; median OS 4.3 [95% CI, 2.5-8.3] months) for patients with hepatic dysfunction, ORR 70% (CR 43%; median OS 8.9 [95% CI, 3.8-NE] months) for patients with renal dysfunction; and ORR 47% (CR 20%, median OS 4 [95% CI, 2.6-6.9] months) for patients with Eastern Cooperative Oncology Group (ECOG) 2 or 3. Multivariate analyses indicated that advanced age (≥65 years vs <65 years; OR 1.38; 95% CI, 1.05-1.83), moderate to severe pulmonary disease (yes vs no; OR 0.74; 95% CI, 0.55-0.98), and ECOG (2-3 vs 0-1; OR 0.31, 95% CI, 0.18-0.53) impacted ORR (Table). Age ≥65 years did not have an impact on survival (HR 1.05, 95% CI, 0.88-1.26), although it was associated with CRS (OR 1.42, 95% CI, 1.03-1.96) and ICANS (OR 1.78, 95% CI, 1.39-2.28). Coexistent cardiac disease (HR 1.44, 95% CI, 1.12-1.83), renal disease (HR 2.13, 95% CI, 1.32-3.46) and hepatic dysfunction (HR 2.65, 95% CI, 1.69-4.14) had an impact on OS, but not on response, CRS, and ICANS. ECOG significantly impacted all efficacy outcomes. None of the other comorbidities tested significantly impacted outcomes. Conclusion: Advanced age (≥65 years) was not associated with worse efficacy outcomes after axi-cel, despite higher rates of CRS and ICANS, which require closer monitoring. Performance status rather than age should be accounted for in patient selection and treatment decisions with axi-cel. Most coexistent organ dysfunctions have no clinically significant impact on axi-cel objective response and safety outcomes. Figure 1 Figure 1. Disclosures Locke: Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Amgen: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; EcoR1: Consultancy; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Wugen: Consultancy, Other; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Umoja: Consultancy, Other; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Cowen: Consultancy; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Legend Biotech: Consultancy, Other; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Janssen: Consultancy, Other: Scientific Advisory Role. Jacobson: Axis: Speakers Bureau; Nkarta: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel support; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Lonza: Consultancy, Honoraria, Other: Travel support; Humanigen: Consultancy, Honoraria, Other: Travel support; Clinical Care Options: Speakers Bureau. Ma: Kite, a Gilead Company: Current Employment. Dong: Kite, a Gilead Company: Current Employment. Hu: Kite, a Gilead Company: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Siddiqi: BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Oncternal: Research Funding; Janssen: Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; TG Therapeutics: Research Funding. Ahmed: Seagen: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Xencor: Research Funding. Ghobadi: Atara: Consultancy; Wugen: Consultancy; Amgen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Celgene: Consultancy. Miklos: Pharmacyclics: Patents & Royalties; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees. Lin: Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Legend: Consultancy; Vineti: Consultancy; Sorrento: Consultancy; Gamida Cell: Consultancy; Janssen: Consultancy, Research Funding; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Merck: Research Funding; Takeda: Research Funding. Perales: Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Nektar Therapeutics: Honoraria, Other; Miltenyi Biotec: Honoraria, Other; MorphoSys: Honoraria; NexImmune: Honoraria; Sellas Life Sciences: Honoraria; Cidara: Honoraria; Merck: Honoraria; Omeros: Honoraria; Servier: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Other; Kite/Gilead: Honoraria, Other; Incyte: Honoraria, Other; Medigene: Honoraria; Karyopharm: Honoraria; Equilium: Honoraria. Lunning: Daiichi-Sankyo: Consultancy; TG Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy; ADC Therapeutics: Consultancy; Spectrum: Consultancy; Beigene: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; Legend: Consultancy; AbbVie: Consultancy; AstraZeneca: Consultancy; Morphosys: Consultancy; Verastem: Consultancy; Novartis: Consultancy; Myeloid Therapeutics: Consultancy; Janssen: Consultancy; Acrotech: Consultancy; Kyowa Kirin: Consultancy; Karyopharm: Consultancy. Hill: Gentenech: Consultancy, Honoraria, Research Funding; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Celgene (BMS): Consultancy, Honoraria, Research Funding. Nikiforow: Kite/Gilead: Other: ad HOC Advisory Boards; Novartis: Other: ad Hoc Advisory Boards; Iovance: Other: ad Hoc Advisory Boards; Glaxo Smith Kline (GSK): Other: ad Hoc Advisory Boards. Xu: Gilead Sciences: Other: stock or other ownership ; Kite, A Gilead Company: Current Employment. Pasquini: Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Kite Pharma: Research Funding; GlaxoSmithKline: Research Funding.