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3. Follicular lymphoma-associated mutations in vacuolar ATPase ATP6V1B2 activate autophagic flux and mTOR

Author

Wang, Fangyang, Gatica, Damian, Ying, Zhang Xiao, Peterson, Luke F., Kim, Peter, Bernard, Denzil, Saiya-Cork, Kamlai, Wang, Shaomeng, Kaminski, Mark S., Chang, Alfred E., Phillips, Tycel, Klionsky, Daniel J., and Malek, Sami N.

Subjects
Care and treatment, Research, Genetic aspects, Follicular cysts -- Genetic aspects -- Care and treatment, ATPases -- Research, B cells -- Research, Cell physiology -- Research, Gene mutation -- Research, Gene mutations -- Research, Adenosine triphosphatase -- Research
Abstract

Introduction Follicular lymphoma (FL) constitutes the most common indolent B cell lymphoma, with an incidence and prevalence of approximately 14,000 and approximately 100,000 cases, respectively, in the US (1). FL [...], The discovery of recurrent mutations in subunits of the vacuolar-type [H.sup.+]-translocating ATPase (v-ATPase) in follicular lymphoma (FL) highlights a role for the amino acid--and energy-sensing pathway to mTOR in the pathogenesis of this disease. Here, through the use of complementary experimental approaches involving mammalian cells and Saccharomyces cerevisiae, we have demonstrated that mutations in the human v-ATPase subunit ATP6V1B2 (also known as Vma2 in yeast) activate autophagic flux and maintain mTOR/TOR in an active state. Engineered lymphoma cell lines and primary FL B cells carrying mutated ATP6V1B2 demonstrated a remarkable ability to survive low leucine concentrations. The treatment of primary FL B cells with inhibitors of autophagy uncovered an addiction for survival for FL B cells harboring ATP6V1B2 mutations. These data support the idea of mutational activation of autophagic flux by recurrent hotspot mutations in ATP6V1B2 as an adaptive mechanism in FL pathogenesis and as a possible new therapeutically targetable pathway.

Published
2019
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4. Activating STAT6 mutations in follicular lymphoma

Author

Yildiz, Mehmet, Li, Hongxiu, Bernard, Denzil, Amin, Nisar A., Ouillette, Peter, Jones, Siân, Saiya-Cork, Kamlai, Parkin, Brian, Jacobi, Kathryn, Shedden, Kerby, Wang, Shaomeng, Chang, Alfred E., Kaminski, Mark S., and Malek, Sami N.

Published
2015
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7. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era

Author

Zhou, Zheng, Sehn, Laurie H., Rademaker, Alfred W., Gordon, Leo I., LaCasce, Ann S., Crosby-Thompson, Allison, Vanderplas, Ann, Zelenetz, Andrew D., Abel, Gregory A., Rodriguez, Maria A., Nademanee, Auayporn, Kaminski, Mark S., Czuczman, Myron S., Millenson, Michael, Niland, Joyce, Gascoyne, Randy D., Connors, Joseph M., Friedberg, Jonathan W., and Winter, Jane N.

Published
2014
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8. Seven-year follow-up for energy/vitality outcomes in early stage Hodgkin’s disease patients treated with subtotal lymphoid irradiation versus chemotherapy plus radiation: SWOG S9133 and its QOL companion study, S9208

Author

Moinpour, Carol M., Unger, Joseph M., Ganz, Patricia A., Kornblith, Alice B., Gaynor, Ellen R., Bowers, Mindy Ann, Gatti, Gretchen S., Kaminski, Mark S., Erba, Harry Paul, Wang, Ting, Yoon, Jihye, Press, Oliver W., and Fisher, Richard I.

Published
2017
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9. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial

Author

Jakubowiak, Andrzej J., Griffith, Kent A., Reece, Donna E., Hofmeister, Craig C., Lonial, Sagar, Zimmerman, Todd M., Campagnaro, Erica L., Schlossman, Robert L., Laubach, Jacob P., Raje, Noopur S., Anderson, Tara, Mietzel, Melissa A., Harvey, Colleen K., Wear, Sandra M., Barrickman, Jennifer C., Tendler, Craig L., Esseltine, Dixie-Lee, Kelley, Susan L., Kaminski, Mark S., Anderson, Kenneth C., and Richardson, Paul G.

Published
2011
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10. Evaluating Acalabrutinib In The Treatment Of Mantle Cell Lymphoma: Design, Development, And Place In Therapy

Author

Girard, Jennifer, Reneau, John, Devata, Sumana, Wilcox, Ryan A, Kaminski, Mark S, Mercer, Jessica, Carty, Shannon, and Phillips, Tycel J

Subjects
immune system diseases, Bruton’s tyrosine kinase, combinations, hemic and lymphatic diseases, mantle cell lymphoma, Review, long-term safety
Abstract

Mantle cell lymphoma (MCL) is an incurable intermediate-grade lymphoma representing 5–6% of non-Hodgkin’s lymphomas diagnosed in the United States. The introduction of inhibitors of Bruton’s tyrosine kinase (BTK) into targeted therapy for MCL has significantly improved outcomes in patients with relapsed/refractory (R/R) disease. Since the initial approval of the first-generation inhibitor, ibrutinib, several second-generation inhibitors have been explored. Acalabrutinib, a second-generation BTK inhibitor, has demonstrated impressive efficacy in clinical trials along with a safety profile that thus far appears improved compared to ibrutinib. The results of a Phase II trial in patients with R/R MCL led to the approval of acalabrutinib in this patient population while fueling further exploration of acalabrutinib in several ongoing clinical trials.

Published
2019

15. Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single-arm, phase 2 study

Author

Wang, Michael, Popplewell, Leslie L., Collins, Robert H., Jr, Winter, Jane N., Goy, Andre, Kaminski, Mark S., Bartlett, Nancy L., Johnston, Patrick B., Lister, John, Fanning, Suzanne R., Tuscano, Joseph M., Beck, Thaddeus J., Kaya, Hakan, Robeva, Anna, Fan, Jenna, Klimovsky, Judith, Cheung, Wing, Cherfi, Azzeddine, and OʼConnor, Owen A.

Published
2014
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18. 131 I-Tositumomab therapy as initial treatment for follicular lymphoma

Author

Kaminski, Mark S., Tuck, Melissa, Estes, Judith, Kolstad, Arne, Ross, Charles, Zasadny, Kenneth, Regan, Denise, Kison, Paul, Fisher, Susan, Kroll, Stewart, and Wahl, Richard L.

Subjects
Chickenpox vaccine -- Usage, Varicella-zoster virus -- Case studies, Varicella-zoster virus -- Observations
Published
2005

34. Clinical application of next generation sequencing in lymphoma.

Author

Scott, Anthony J., Tokaz, Molly C., Shango, Maryann, Devata, Sumana, Carty, Shannon A., Kaminski, Mark S., Chinnaiyan, Arul M., Phillips, Tycel J., and Wilcox, Ryan A.

Subjects
LYMPHOMAS, TREATMENT effectiveness, DISEASE progression, TIME trials, CLINICAL trials
Abstract

Successful treatment of relapsed/refractory and rare subtypes of lymphomas remains a therapeutic challenge. Though the use of tumor profiling is increasing, little is described about how providers ultimately utilize this information in clinical decision-making. We reviewed 92 adult lymphoma patients who underwent an IRB-approved tumor sequencing protocol at the University of Michigan, MI-ONCOSEQ. Of this cohort, 60 had a targeted treatment suggested by their test results, and 11 patients ultimately underwent the MI-ONCOSEQ recommended therapy. One obtained complete response based on precision treatment recommendations. The two main barriers for targeted treatment utilization included inopportune timing (the patient either was sequenced too early or too late in their disease course) and clinical trial availability. While this study demonstrates the success of sequencing lymphomas for the identification of novel therapies, it also underlines the clinical challenges, namely the optimal timing and availability of trials, inherent in the successful application of this technology. [ABSTRACT FROM AUTHOR]

Published
2021
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37. Impact of a vincristine dose cap on the incidence of neuropathies with DA-EPOCH-R for the treatment of aggressive lymphomas.

Author

Weis, Taylor M., Marini, Bernard L., Nachar, Victoria R., Brown, Anna M., Phillips, Tycel J., Brown, Julia, Wilcox, Ryan A., Kaminski, Mark S., Devata, Sumana, and Perissinotti, Anthony J.

Subjects
VINCRISTINE, NEUROPATHY, COHORT analysis
Abstract

The CALGB/Alliance 50303 trial found a fivefold increase in the rate of severe neuropathies with DA-EPOCH-R compared to R-CHOP. A likely cause is a higher, uncapped dose of vincristine which is unique to DA-EPOCH-R. Due to a potential for increased toxicity and a paucity of literature confirming improved efficacy with higher vincristine doses, our institution implemented a 2 mg vincristine dose cap with DA-EPOCH-R. We conducted a single-center, retrospective cohort study assessing rates of neuropathy in patients receiving DA-EPOCH-R with or without a 2 mg vincristine dose cap. Patients who received a 2 mg vincristine dose cap had a significant reduction in the incidence of grade 2+ neuropathy (40.9% vs. 84.1%, p =.001) and a significantly longer time to onset of grade 2+ neuropathy (not reached vs. 63 days, p =.001). A vincristine dose cap of 2 mg per cycle may reduce the neurotoxicity-associated morbidity of DA-EPOCH-R. [ABSTRACT FROM AUTHOR]

Published
2020
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40. Multicentre retrospective study of intravascular large B‐cell lymphoma treated at academic institutions within the United States.

Author

Geer, Marcus, Roberts, Emily, Shango, Maryann, Till, Brian G., Smith, Stephen D., Abbas, Hashim, Hill, Brian T., Kaplan, Jason, Barr, Paul M., Caimi, Paolo, Stephens, Deborah M., Lin, Emily, Herrera, Alex F., Rosenbaum, Evan, Amengual, Jennifer E., Boonstra, Philip S., Devata, Sumana, Wilcox, Ryan A., Kaminski, Mark S., and Phillips, Tycel J.

Subjects
LYMPHOMAS, THERAPEUTICS, RETROSPECTIVE studies, U.S. states
Abstract

Summary: Intravascular large B‐cell lymphoma (IVLBCL) is a rare entity, with a generally aggressive course that may vary based on geographic presentation. While a United States (US) registry study showed relatively good outcomes with IVLBCL, clinicopathological and treatment data were unavailable. We performed a detailed retrospective review of cases identified at 8 US medical centres, to improve understanding of IVLBCL and inform management. We compiled data retrieved via an Institutional Review Board‐approved review of IVLBCL cases identified from 1999 to 2015 at nine academic institutions across the US. We characterized the cohort's clinical status at time of diagnosis, presenting diagnostic and clinical features of the disease, treatment modalities used and overall prognostic data. Our cohort consisted of 54 patients with varying degrees of clinical features. Adjusting for age, better performance status at presentation was associated with increased survival time for the patients diagnosed in vivo (hazard ratio: 2·12, 95% confidence interval 1·28, 3·53). Based on the data we have collected, it would appear that the time interval to diagnosis is a significant contributor to outcomes of patients with IVLBCL. [ABSTRACT FROM AUTHOR]

Published
2019
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41. Obinutuzumab plus CHOP is effective and has a tolerable safety profile in previously untreated, advanced diffuse large B-cell lymphoma: the phase II GATHER study.

Author

Sharman, Jeff P., Forero-Torres, Andres, Costa, Luciano J., Flinn, Ian W., Inhorn, Lowell, Kelly, Kevin, Bessudo, Alberto, Fayad, Luis E., Kaminski, Mark S., Evens, Andrew M., Flowers, Christopher R., Sahin, Deniz, Mundt, Kirsten E., Sandmann, Thomas, Fingerle-Rowson, Günter, Vignal, Charlotte, Mobasher, Mehrdad, and Zelenetz, Andrew D.

Subjects
LYMPHOMAS, CANCER treatment, DOXORUBICIN, CLINICAL trials
Abstract

This study investigated the safety and efficacy of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) in patients with advanced diffuse large B-cell lymphoma (DLBCL) and explored the impact of cell-of-origin (COO) on patient outcomes. Patients (N = 100) received obinutuzumab (1000 mg on the days 1, 8, and 15 of cycle 1, and day 1 of cycles 2–8) plus CHOP (cycles 1–6). For patients without grade ≥3 infusion-related reactions (IRRs) to standard-rate obinutuzumab infusion, a shorter duration of infusion (SDI) was evaluated. Overall and complete response rates, as determined according to the Cheson et al. criteria by investigators/independent radiological facility, were 82.0/75.0% and 55.0/58.0%, respectively. SDI of 120 minutes and 90 minutes were well tolerated with no grade ≥3 IRRs. Among all patients, IRRs typically occurred during cycle 1, day 1. G-CHOP is active and has an acceptable safety profile in the first-line treatment of patients with advanced DLBCL. Clinical Trials: NCT01414855DLBCL [ABSTRACT FROM AUTHOR]

Published
2019
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43. The physical exam's role in determining dose-limiting toxicity prior to immunochemotherapy administration in lymphoma.

Author

Runge, John S., Brown, Anna B., Phillips, Tycel J., Kaminski, Mark S., Carty, Shannon A., and Wilcox, Ryan A.

Subjects
THERAPEUTIC use of antineoplastic agents, PHYSICAL diagnosis, DRUG dosage, DRUG tolerance, CANCER chemotherapy, RETROSPECTIVE studies, DESCRIPTIVE statistics, LYMPHOMAS, IMMUNOTHERAPY, DRUG toxicity
Abstract

Introduction: The COVID-19 pandemic has introduced new challenges to healthcare access and delivery. It is critical to identify areas for innovation within oncologic clinical practice to maintain high quality care. We evaluated the potential utility of telemedicine initiatives for patients with lymphoma undergoing immunochemotherapy. We conducted a retrospective review of adult lymphoma patients receiving R-CHOP + /- R, R-ICE, R-GEMOX, and R-DHAP at our institution in the last three years (2017-2019) and identified cycles for which dose modifications were required. Methods: We reviewed 1290 total treatment cycles in 301 unique patients, 1102 cycles (85.4%) were R-CHOP + /- R, 105 (8.1%) were R-ICE, 71 (5.5%) were R-GEMOX, and 12 (0.9%) were R-DHAP. We identified that 144 cycles (11.2%) were subject to dosing adjustments. We retrospectively reviewed laboratory results, patient history, and/or physical exam findings that informed dose modifications. Results: Of the 144 dose adjustments, 11% of cycles contained dose increases due to a well-tolerated previous dose noted in the clinical assessment. The remaining 128 modified cycles were dose reductions. Notably, only 7/128 dose reductions were based on physical exam findings alone, due solely to a change in patient body weight. As patients are routinely weighed immediately prior to chemotherapy administration, effectively no dose modifications (0/144) were exclusively based on abnormal physical exam finding during a pre-infusion assessment. Conclusion: These findings suggest that pre-infusion assessments may be amenable to virtual visits for lymphoma patients undergoing immunochemotherapy. [ABSTRACT FROM AUTHOR]

Published
2023
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44. Resolution of Peripheral Neuropathy (PN) in Patients Who Received A+AVD or ABVD in the Phase 3 ECHELON-1 Trial

Author

Radford, John, Connors, Joseph M., Younes, Anas, Gallamini, Andrea, Ansell, Stephen M., Kim, Won Seog, Gopal, Ajay K., Kaminski, Mark S, Cheong, June Won, Flinn, Ian W., Kalakonda, Nagesh, Pettengell, Ruth, Dlugosz-Danecka, Monika, Engley, Gerald, Fenton, Keenan, Liu, Rachael, Purevjal, Indra, Miao, Harry, Gautam, Ashish, and Kuruvilla, John

Published
2018
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45. Ruxolitinib Is Active and Well Tolerated in Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis: Preliminary Results of an Ongoing, Open-Label, Single Center Study

Author

Alsawah, Fares, Merrill, Samuel A., Bockenstedt, Paula L., Campagnaro, Erica L., Devata, Sumana, Gitlin, Scott D., Kaminski, Mark S, Cusick, Alice M., Phillips, Tycel J., Sood, Suman L., Talpaz, Moshe, Quiery, Albert Thomas, Boonstra, Philip S, Ahmed, Asra Z., and Wilcox, Ryan A.

Published
2018
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46. Subclonal Mutations of TP53 Are Common in Untreated Follicular Lymphoma and Mutation Status Is Predictive of PFS When CHOP Is Combined with 131-Iodine Tositumomab but Not with Rituximab: An Analysis of SWOG S0016

Author

Burack, Richard, Li, Hongli, Spence, Janice M, Adlowitz, Diana, Rimsza, Lisa M., Braziel, Rita M., Spier, Catherine M., Kaminski, Mark S, Leonard, John P., Fisher, Richard I., Leblanc, Michael L., Smith, Sonali M., and Friedberg, Jonathan W.

Published
2018
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49. Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016.

Author

Shadman, Mazyar, Li, Hongli, Rimsza, Lisa, Leonard, John P., Kaminski, Mark S., Braziel, Rita M., Spier, Catherine M., Gopal, Ajay K., Maloney, David G., Cheson, Bruce D., Dakhil, Shaker, LeBlanc, Michael, Smith, Sonali M., Fisher, Richard I., Friedberg, Jonathan W., and Press, Oliver W.

Published
2018
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50. Multicenter Retrospective Study of Features and Outcomes of Patients with Intravascular DLBCL Treated at Academic Institutions within the United States

Author

Geer, Marcus, Shango, Maryann, Till, Brian G., Smith, Stephen D., Abbas, Hashim, Hill, Brian T., Kaplan, Jason, Barr, Paul M., Caimi, Paolo, Stephens, Deborah M., Lin, Emily, Herrera, Alex F., Rosenbaum, Evan, Amengual, Jennifer E, Roberts, Emily, Boonstra, Philip S, Devata, Sumana, Wilcox, Ryan A., Kaminski, Mark S, and Phillips, Tycel J.

Published
2017
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