Browsing by Author "Kumar, Shaji"

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    Age no Bar – a CIBMTR analysis of Elderly Patients undergoing Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
    (Wiley, 2020) Munshi, Pashna N.; Vesole, David; Jurczyszyn, Artur; Zaucha, Jan Maciej; St. Martin, Andrew; Davila, Omar; Agrawal, Vaibhav; Badawy, Sherif M.; Battiwalla, Minoo; Chhabra, Saurabh; Copelan, Edward; Kharfan-Dabaja, Mohamed A.; Farhadfar, Nosha; Ganguly, Siddhartha; Hashmi, Shahrukh; Krem, Maxwell M.; Lazarus, Hillard M.; Malek, Ehsan; Meehan, Kenneth; Murthy, Hemant S.; Nishihori, Taiga; Olin, Rebecca L.; Olsson, Richard F.; Schriber, Jeffrey; Seo, Sachiko; Shah, Gunjan; Solh, Melhem; Tay, Jason; Kumar, Shaji; Qazilbash, Muzaffar H.; Shah, Nina; Hari, Parameswaran N.; D'Souza, Anita; Medicine, School of Medicine
    Background: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2 . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2 , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P = .01]), likely representing frailty. Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
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    ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Multiple Myeloma
    (Elsevier, 2022) Dhakal, Binod; Shah, Nina; Kansagra, Ankit; Kumar, Ambuj; Lonial, Sagar; Garfall, Alfred; Cowan, Andrew; Poudyal, Bishesh Sharma; Costello, Caitlin; Gay, Francesca; Cook, Gordon; Quach, Hang; Einsele, Herman; Schriber, Jeff; Hou, Jian; Costa, Luciano; Aljurf, Mahmoud; Chaudhry, Maria; Beksac, Meral; Prince, Miles; Mohty, Mohamad; Janakiram, Murali; Callander, Natalie; Biran, Noa; Malhotra, Pankaj; Rodriguez Otero, Paula; Moreau, Philippe; Abonour, Rafat; Iftikhar, Raheel; Silberman, Rebecca; Mailankody, Sham; Gregory, Tara; Lin, Yi; Carpenter, Paul; Hamadani, Mehdi; Usmani, Saad; Kumar, Shaji; Medicine, School of Medicine
    Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.
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    Examining allostatic load, neighborhood socioeconomic status, symptom burden and mortality in multiple myeloma patients
    (Springer, 2022-04-01) Obeng-Gyasi, Samilia; Graham, Noah; Kumar, Shaji; Lee, Ju-Whei; Jacobus, Susanna; Weiss, Matthias; Cella, David; Zhao, Fengmin; Ip, Edward H.; O’Connell, Nathaniel; Hong, Fangxin; Peipert, Devin J.; Gareen, IIana F.; Timsina, Lava R.; Gray, Robert; Wagner, Lynne I.; Carlos, Ruth C.; Surgery, School of Medicine
    The objective of this study is to examine the association between neighborhood socioeconomic status (nSES) and baseline allostatic load (AL) and clinical trial endpoints in patients enrolled in the E1A11 therapeutic trial in multiple myeloma (MM). Study endpoints were symptom burden (pain, fatigue, and bother) at baseline and 5.5 months, non-completion of induction therapy, overall survival (OS) and progression-free survival (PFS). Multivariable logistic and Cox regression examined associations between nSES, AL and patient outcomes. A 1-unit increase in baseline AL was associated with greater odds of high fatigue at baseline (adjusted OR [95% CI] = 1.21 [1.08–1.36]) and a worse OS (adjusted hazard ratio, [95% CI] = 1.21 [1.06–1.37]). High nSES was associated with worse baseline bother (middle OR = 4.22 [1.11–16.09] and high 4.49 [1.16–17.43]) compared to low nSES. There was no association between AL or nSES and symptom burden at 5.5 months, non-completion of induction therapy or PFS. Additionally, there was no association between nSES and OS. AL may have utility as a predictive marker for OS among patients with MM and may allow individualization of treatment. Future studies should standardize and validate AL patients with MM.
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    Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma
    (Springer Nature, 2023-12-07) Mitra, Amit Kumar; Mukherjee, Ujjal Kumar; Mazumder, Suman; Madhira, Vithal; Bergquist, Timothy; Shao, Yu Raymond; Liu, Feifan; Song, Qianqian; Su, Jing; Kumar, Shaji; Bates, Benjamin A.; Sharafeldin, Noha; Topaloglu, Umit; National COVID Cohort Collaborative Consortium; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.
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    The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms
    (Springer Nature, 2022) Alaggio, Rita; Amador, Catalina; Anagnostopoulos, Ioannis; Attygalle, Ayoma D.; Araujo, Iguaracyra Barreto de Oliveira; Berti, Emilio; Bhagat, Govind; Borges, Anita Maria; Boyer, Daniel; Calaminici, Mariarita; Chadburn, Amy; Chan, John K. C.; Cheuk, Wah; Chng, Wee-Joo; Choi, John K.; Chuang, Shih-Sung; Coupland, Sarah E.; Czader, Magdalena; Dave, Sandeep S.; de Jong, Daphne; Du, Ming-Qing; Elenitoba-Johnson, Kojo S.; Ferry, Judith; Geyer, Julia; Gratzinger, Dita; Guitart, Joan; Gujral, Sumeet; Harris, Marian; Harrison, Christine J.; Hartmann, Sylvia; Hochhaus, Andreas; Jansen, Patty M.; Karube, Kennosuke; Kempf, Werner; Khoury, Joseph; Kimura, Hiroshi; Klapper, Wolfram; Kovach, Alexandra E.; Kumar, Shaji; Lazar, Alexander J.; Lazzi, Stefano; Leoncini, Lorenzo; Leung, Nelson; Leventaki, Vasiliki; Li, Xiao-Qiu; Lim, Megan S.; Liu, Wei-Ping; Louissai, Abnerm, Jr.; Marcogliese, Andrea; Medeiros, L. Jeffrey; Michal, Michael; Miranda, Roberto N.; Mitteldorf, Christina; Montes-Moreno, Santiago; Morice, William; Nardi, Valentina; Naresh, Kikkeri N.; Natkunam, Yasodha; Ng, Siok-Bian; Oschlies, Ilske; Ott, German; Parrens, Marie; Pulitzer, Melissa; Rajkumar, S. Vincent; Rawstron, Andrew C.; Rech, Karen; Rosenwald, Andreas; Said, Jonathan; Sarkozy, Clémentine; Sayed, Shahin; Saygin, Caner; Schuh, Anna; Sewell, William; Siebert, Reiner; Sohani, Aliyah R.; Tooze, Reuben; Traverse-Glehen, Alexandra; Vega, Francisco; Vergier, Beatrice; Wechalekar, Ashutosh D.; Wood, Brent; Xerri, Luc; Xiao, Wenbin; Pathology and Laboratory Medicine, School of Medicine
    We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.