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2. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024

Author

Wierda, William G., primary, Brown, Jennifer, additional, Abramson, Jeremy S., additional, Awan, Farrukh, additional, Bilgrami, Syed F., additional, Bociek, Greg, additional, Brander, Danielle, additional, Cortese, Matthew, additional, Cripe, Larry, additional, Davis, Randall S., additional, Eradat, Herbert, additional, Fakhri, Bita, additional, Fletcher, Christopher D., additional, Gaballa, Sameh, additional, Hamid, Muhammad Saad, additional, Hill, Brian, additional, Kaesberg, Paul, additional, Kahl, Brad, additional, Kamdar, Manali, additional, Kipps, Thomas J., additional, Ma, Shuo, additional, Mosse, Claudio, additional, Nakhoda, Shazia, additional, Parikh, Sameer, additional, Schorr, Andrew, additional, Schuster, Stephen, additional, Seshadri, Madhav, additional, Siddiqi, Tanya, additional, Stephens, Deborah M., additional, Thompson, Meghan, additional, Ujjani, Chaitra, additional, Valdez, Riccardo, additional, Wagner-Johnston, Nina, additional, Woyach, Jennifer A., additional, Sundar, Hema, additional, and Dwyer, Mary, additional

Published
2024
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3. Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma

Author

Merryman, Reid W., Redd, Robert A., Nishihori, Taiga, Chavez, Julio, Nieto, Yago, Darrah, Justin M., Rao, Uttam, Byrne, Michael T., Bond, David A., Maddocks, Kami J., Spinner, Michael A., Advani, Ranjana H., Ballard, Hatcher J., Svoboda, Jakub, Singh, Anurag K., McGuirk, Joseph P., Modi, Dipenkumar, Ramchandren, Radhakrishnan, Romancik, Jason, Cohen, Jonathon B., Frigault, Matthew J., Chen, Yi-Bin, Serritella, Anthony V., Kline, Justine, Ansell, Stephen, Nathan, Sunita, Rahimian, Maryam, Joyce, Robin M., Shah, Mansi, David, Kevin A., Park, Steven, Beaven, Anne W., Habib, Alma, Bachanova, Veronika, Nakhoda, Shazia, Khan, Nadia, Lynch, Ryan C., Smith, Stephen D., Ho, Vincent T., LaCasce, Ann, Armand, Philippe, and Herrera, Alex F.

Published
2021
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4. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial

Author

Budde, Lihua E., primary, Olszewski, Adam J., additional, Assouline, Sarit, additional, Lossos, Izidore S., additional, Diefenbach, Catherine, additional, Kamdar, Manali, additional, Ghosh, Nilanjan, additional, Modi, Dipenkumar, additional, Sabry, Waleed, additional, Naik, Seema, additional, Mehta, Amitkumar, additional, Nakhoda, Shazia K., additional, Smith, Stephen D., additional, Dorritie, Kathleen, additional, Jia, Ting, additional, Pham, Song, additional, Huw, Ling-Yuh, additional, Jing, Jing, additional, Wu, Hao, additional, Ead, Wahib S., additional, To, Iris, additional, Batlevi, Connie Lee, additional, Wei, Michael C., additional, and Chavez, Julio C., additional

Published
2023
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6. ABCL-455 Multicenter Retrospective Analysis of Single-Route Prophylaxis in Aggressive B-Cell Lymphomas

Author

Orellana-Noia, Victor, Reed, Daniel, McCook, Ashley, Sen, Jeremy, Barlow, Christian, Malecek, Mary-Kate, Watkins, Marcus, Kahl, Brad, Spinner, Michael, Advani, Ranjana, Voorhees, Timothy, Snow, Anson, Grover, Natalie, Ayers, Amy, Romancik, Jason, Liu, Yuxin, Huntington, Scott, Chavez, Julio, Saeed, Hayder, Lazaryan, Aleksandr, Raghunathan, Vikram, Spurgeon, Stephen, Ollila, Thomas, Prete, Christopher Del, Olszewski, Adam, Ayers, Emily, Landsburg, Daniel, Echalier, Benjamin, Lee, Jun, Kamdar, Manali, Calmi, Paolo, Fu, Timothy, Liu, Jieqi, David, Kevin, Alharthy, Hanan, Law, Jennie, Karmali, Reem, Shah, Harsh, Stephens, Deborah, Major, Ajay, Rojek, Alexandra, Smith, Sonali, Yellala, Amulya, Kallam, Ayvakta, Nakhoda, Shazia, Khan, Nadia, Sohail, Mohammad, Hill, Brian, Barrett-Campbell, Odeth, Lansigan, Frederick, Switchenko, Jeffrey, Cohen, Jonathon, and Portell, Craig

Published
2022
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10. A Phase I Trial Assessing the Feasibility of Romidepsin Combined with Brentuximab Vedotin for Patients Requiring Systemic Therapy for Cutaneous T-Cell Lymphoma

Author

Barta, Stefan K., primary, Feldman, Tatyana A., additional, DeSimone, Jennifer A., additional, Kim, Ellen, additional, Devajaran, Karthik, additional, Yang, Yibin, additional, Fung, Henry C., additional, Mahvish, Tafseer, additional, Nakhoda, Shazia, additional, and Khan, Nadia, additional

Published
2022
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11. Poster: ABCL-455 Multicenter Retrospective Analysis of Single-Route Prophylaxis in Aggressive B-Cell Lymphomas

Author

Orellana-Noia, Victor, primary, Reed, Daniel, additional, McCook, Ashley, additional, Sen, Jeremy, additional, Barlow, Christian, additional, Malecek, Mary-Kate, additional, Watkins, Marcus, additional, Kahl, Brad, additional, Spinner, Michael, additional, Advani, Ranjana, additional, Voorhees, Timothy, additional, Snow, Anson, additional, Grover, Natalie, additional, Ayers, Amy, additional, Romancik, Jason, additional, Liu, Yuxin, additional, Huntington, Scott, additional, Chavez, Julio, additional, Saeed, Hayder, additional, Lazaryan, Aleksandr, additional, Raghunathan, Vikram, additional, Spurgeon, Stephen, additional, Ollila, Thomas, additional, Prete, Christopher Del, additional, Olszewski, Adam, additional, Ayers, Emily, additional, Landsburg, Daniel, additional, Echalier, Benjamin, additional, Lee, Jun, additional, Kamdar, Manali, additional, Caimi, Paolo, additional, Fu, Timothy, additional, Liu, Jieqi, additional, David, Kevin, additional, Alharthy, Hanan, additional, Law, Jennie, additional, Karmali, Reem, additional, Shah, Harsh, additional, Stephens, Deborah, additional, Major, Ajay, additional, Rojek, Alexandra, additional, Smith, Sonali, additional, Yellala, Amulya, additional, Kallam, Ayvakta, additional, Nakhoda, Shazia, additional, Khan, Nadia, additional, Sohail, Mohammad, additional, Hill, Brian, additional, Barrett-Campbell, Odeth, additional, Lansigan, Frederick, additional, Switchenko, Jeffrey, additional, Cohen, Jonathon, additional, and Portell, Craig, additional

Published
2022
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12. Resistance to BTK inhibition in CLL and non-Hodgkin lymphoma

Author

Nakhoda, Shazia, Vistarop, Aldana, and Wang, Y. Lynn

Subjects
Article
Abstract

Bruton tyrosine kinase inhibitors (BTKi) have transformed the therapeutic landscape of chronic lymphocytic leukemia (CLL) and Non-Hodgkin lymphoma (NHL). However, primary and acquired resistance to BTKi can be seen due to a variety of mechanisms including tumor intrinsic and extrinsic mechanisms such as gene mutations, activation of bypass signaling pathways, and tumor microenvironment. Herein, we provide an updated review of the key clinical data of BTKi treatment in CLL, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). We incorporate the most recent findings regarding mechanisms of resistance to covalent and non-covalent inhibitors, including ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib. We also cover the clinical sensitivity of certain molecular subtypes of DLBCL to an ibrutinib-containing regimen. Lastly, we summarize ongoing clinical investigations aimed at overcoming resistance via use of BTKi-containing combination therapies or the novel non-covalent BTK inhibitors. The review article targets an audience of clinical practitioners, clinical investigators, and translational researchers.

Published
2022

16. Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non‐Hodgkin lymphoma.

Author

Nakhoda, Shazia, Vistarop, Aldana, and Wang, Y. Lynn

Subjects
*BRUTON tyrosine kinase, *CHRONIC leukemia, *LYMPHOCYTIC leukemia, *NON-Hodgkin's lymphoma, *DIFFUSE large B-cell lymphomas
Abstract

Summary: Bruton tyrosine kinase inhibitors (BTKi) have transformed the therapeutic landscape of chronic lymphocytic leukaemia (CLL) and non‐Hodgkin lymphoma. However, primary and acquired resistance to BTKi can be seen due to a variety of mechanisms including tumour intrinsic and extrinsic mechanisms such as gene mutations, activation of bypass signalling pathways and tumour microenvironment. Herein, we provide an updated review of the key clinical data of BTKi treatment in CLL, mantle cell lymphoma, and diffuse large B‐cell lymphoma (DLBCL). We incorporate the most recent findings regarding mechanisms of resistance to covalent and non‐covalent inhibitors, including ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib. We also cover the clinical sensitivity of certain molecular subtypes of DLBCL to an ibrutinib‐containing regimen. Lastly, we summarise ongoing clinical investigations aimed at overcoming resistance via use of BTKi‐containing combined therapies or the novel non‐covalent BTKi. The review article targets an audience of clinical practitioners, clinical investigators and translational researchers. [ABSTRACT FROM AUTHOR]

Published
2023
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19. CNS Prophylaxis during Front-Line Therapy in Aggressive Non-Hodgkin Lymphomas: Real-World Outcomes and Practice Patterns from 19 US Academic Institutions

Author

Orellana-Noia, Victor M., primary, Reed, Daniel R, additional, Sen, Jeremy M, additional, Barlow, Christian, additional, Malecek, Mary-Kate, additional, Kahl, Brad S., additional, Spinner, Michael A, additional, Advani, Ranjana, additional, Voorhees, Timothy J, additional, Snow, Anson, additional, Grover, Natalie S, additional, Ayers, Amy, additional, Romancik, Jason T., additional, Liu, Yuxin, additional, Huntington, Scott F., additional, Chavez, Julio C., additional, Saeed, Hayder, additional, Lazaryan, Aleksandr, additional, Raghunathan, Vikram, additional, Spurgeon, Stephen E., additional, Ollila, Thomas A, additional, Del Prete, Christopher, additional, Olszewski, Adam J, additional, Ayers, Emily C., additional, Landsburg, Daniel J., additional, Echalier, Benjamin, additional, Lee, Jun, additional, Kamdar, Manali, additional, Caimi, Paolo F, additional, Fu, Timothy, additional, Liu, Jieqi, additional, David, Kevin A., additional, Alharthy, Hanan, additional, Law, Jennie Y., additional, Karmali, Reem, additional, Shah, Harsh, additional, Stephens, Deborah M., additional, Major, Ajay, additional, Rojek, Alexandra E, additional, Smith, Sonali M., additional, Yellala, Amulya, additional, Kallam, Avyakta, additional, Nakhoda, Shazia, additional, Khan, Nadia, additional, Cohen, Jonathon B., additional, and Portell, Craig A., additional

Published
2020
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22. Fixed Duration Mosunetuzumab Plus Polatuzumab Vedotin Has Promising Efficacy and a Manageable Safety Profile in Patients with BTKi Relapsed/Refractory Mantle Cell Lymphoma: Initial Results from a Phase Ib/II Study

Author

Wang, Michael L., Assouline, Sarit, Kamdar, Manali, Ghosh, Nilanjan, Naik, Seema, Nakhoda, Shazia K., Chavez, Julio C., Jia, Ting, Pham, Song, Huw, Ling-Yuh, Jing, Jing, Ead, Wahib, To, Iris, Batlevi, Connie Lee, Wei, Michael C., and Budde, L. Elizabeth

Abstract

Background:New treatment options are needed for patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL), especially for pts with progressive disease (PD) after Bruton's tyrosine kinase inhibitor (BTKi) therapy. Outcomes for R/R MCL pts with PD after the BTKi ibrutinib are very poor, demonstrated by a median overall survival of 2.9 months (Martin et al. Blood 2016). While chimeric antigen receptor (CAR) T-cell therapies are approved for pts with R/R MCL; treatment is associated with high toxicity and difficulty with accessibility. Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that engages and redirects T cells to eliminate malignant B cells. Polatuzumab vedotin (Pola) is a CD79b-targeted antibody-drug conjugate that inhibits cell division and induces apoptosis in B cells. This ongoing Phase Ib/II study (NCT03671018) is investigating Mosun in combination with Pola (M-Pola) in pts with R/R B cell non-Hodgkin lymphoma. Here, we report initial safety and efficacy data from an ongoing Phase II expansion cohort of pts with R/R MCL who had received prior BTKi therapy.

Published
2023
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23. Mosunetuzumab Plus Polatuzumab Vedotin Demonstrates a Favorable Safety Profile and Efficacy in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Primary Analysis of a Phase Ib/II Study

Author

Budde, L. Elizabeth, Olszewski, Adam J, Assouline, Sarit, Lossos, Izidore S., Diefenbach, Catherine, Kamdar, Manali, Ghosh, Nilanjan, Modi, Dipenkumar, Sabry, Waleed, Naik, Seema, Mehta, Amitkumar, Nakhoda, Shazia K., Smith, Stephen D, Dorritie, Kathleen, Jia, Ting, Pham, Song, Huw, Ling-Yuh, Wu, Hao, To, Iris, Wei, Michael C., and Chavez, Julio C.

Abstract

Background:Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that engages and redirects T cells to eliminate malignant B cells. The ongoing Phase Ib/II GO40516 study (NCT03671018) investigates Mosun in combination with polatuzumab vedotin (Pola; M-Pola) in pts with B-cell non-Hodgkin lymphoma (B-NHL). The Phase II expansion phase of the M-Pola regimen (with conventional Mosun and Pola dose and dose schedule), showed an acceptable safety profile and promising anti-tumor activity in pts with R/R B-NHL at interim analysis (Budde et al. ASH 2021). With enrollment complete, we present full dose-expansion cohort results.

Published
2023
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24. Iris Nevus Growth into Melanoma: Analysis of 1611 Consecutive Eyes

Author

Shields, Carol L., primary, Kaliki, Swathi, additional, Hutchinson, Anne, additional, Nickerson, Stephanie, additional, Patel, Jinali, additional, Kancherla, Swarupa, additional, Peshtani, Ani, additional, Nakhoda, Shazia, additional, Kocher, Kristen, additional, Kolbus, Emily, additional, Jacobs, Emily, additional, Garoon, Robert, additional, Walker, Brianna, additional, Rogers, Brittany, additional, and Shields, Jerry A., additional

Published
2013
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25. Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL).

Author

Kim PM, Nejati R, Lu P, Thakkar D, Mackrides N, Dupoux V, Nakhoda S, Baldwin DA, Pei J, Dave SS, Wang YL, and Wasik MA

Subjects
Humans, Rituximab, Genomics, Neoplasm Recurrence, Local, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Aniline Compounds, Piperidines
Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B , MyD88 , TP53 , TBL1XR1 , and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance., (© 2023 Kim et al.; Published by Cold Spring Harbor Laboratory Press.)

Published
2024
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26. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial.

Author

Budde LE, Olszewski AJ, Assouline S, Lossos IS, Diefenbach C, Kamdar M, Ghosh N, Modi D, Sabry W, Naik S, Mehta A, Nakhoda SK, Smith SD, Dorritie K, Jia T, Pham S, Huw LY, Jing J, Wu H, Ead WS, To I, Batlevi CL, Wei MC, and Chavez JC

Subjects
Humans, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antibodies, Monoclonal, Immunoconjugates adverse effects, Lymphoma, Large B-Cell, Diffuse drug therapy, Antineoplastic Agents therapeutic use
Abstract

Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody-drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8-69.0) and 45.9% (45/98; 95% CI: 35.8-56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5-not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2-18.7). Median overall survival was 23.3 months (95% CI: 14.8-NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 ., (© 2023. The Author(s).)

Published
2024
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