201 results on '"Oki, Yasuhiro"'
Search Results
2. A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL
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Cherng, Hua-Jay J., Alig, Stefan K., Oki, Yasuhiro, Nastoupil, Loretta J., Fayad, Luis, Neelapu, Sattva S., Turturro, Francesco, Hagemeister, Fredrick, Craig, Alexander F. M., Macaulay, Charles W., Rodriguez, Maria Alma, Lee, Hun Ju, McDonnell, Timothy J., Flowers, Christopher R., Vega, Francisco, Green, Michael R., Feng, Lei, Kurtz, David M., Alizadeh, Ash A., Davis, R. Eric, and Westin, Jason R.
- Abstract
Diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, one-third of patients experience refractory or relapsed disease. Studies comparing R-CHOP with modified regimens replacing R with obinutuzumab (O) or adding lenalidomide (L) did not result in improved outcomes; however, L and O together may enhance natural killer-cell mediated antibody-dependent cellular toxicity when paired with CHOP. Here, we report on a phase 1b/2 study of 53 patients with newly diagnosed DLBCL who received 6 cycles of LO-CHOP. The end of treatment overall and complete response rates of the 50 evaluable patients were 98% and 90%, respectively. After a median follow-up of 4.5 years, the 4-year progression free and overall survival rates were 87.4% and 91.3%, respectively. Grade 3 to 4 adverse events were experienced by 70% of patients, including neutropenia (38%), thrombocytopenia (17%), fatigue (13%), and neutropenic fever (13%). Of the 33 patients profiled with circulating tumor DNA (ctDNA) sequencing, 31 (94%) had detectable pretreatment ctDNA with cancer personalized profiling by deep sequencing, 24 (73%) were classifiable by the LymphGen classifier, and 15/20 (75%) and 12/17 (71%) patients achieved early and major molecular responses after 1 and 2 cycles, respectively. Using phased variant enrichment and detection sequencing, 16/18 evaluable patients (89%) showed no detectable ctDNA after at least 5 cycles of LO-CHOP. LO-CHOP demonstrates high efficacy and tolerability in newly diagnosed DLBCL, leading to a high rate of undetectable minimal residual disease by ctDNA. This trial has been registered at www.clinicaltrials.gov as NCT02529852.
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- 2023
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3. Updated Results of an Investigator-Initiated Phase II Study of Pembrolizumab and Romidepsin for Patients with Relapsed or Refractory T-Cell Lymphoma (TCL) with Survival Analysis
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Agbedia, Owhofasa O., Prakash, Rishab, Xu, Jie, Becnel, Melody R., Nair, Ranjit, Steiner, Raphael E, Feng, Lei, Lee, Hun Ju, Strati, Paolo, Ahmed, Sairah, Parmar, Simrit, Nieto, Yago, Hosing, Chitra, Westin, Jason, Nastoupil, Loretta J., Vo, Ann, Samaniego, Felipe, Fowler, Nathan H., Saini, Neeraj, Khouri, Issa F., Im, Jin S., Fayad, Luis, Jain, Preetesh, Wang, Michael L., Miranda, Roberto N., Vega, Francisco, Medeiros, Jeffrey, Oki, Yasuhiro, Flowers, Christopher R., Neelapu, Sattva S., and Iyer, Swaminathan P.
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- 2022
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4. Updated Results of an Investigator-Initiated Phase II Study of Pembrolizumab and Romidepsin for Patients with Relapsed or Refractory T-Cell Lymphoma (TCL) with Survival Analysis
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Agbedia, Owhofasa O., Prakash, Rishab, Xu, Jie, Becnel, Melody R., Nair, Ranjit, Steiner, Raphael E, Feng, Lei, Lee, Hun Ju, Strati, Paolo, Ahmed, Sairah, Parmar, Simrit, Nieto, Yago, Hosing, Chitra, Westin, Jason, Nastoupil, Loretta J., Vo, Ann, Samaniego, Felipe, Fowler, Nathan H., Saini, Neeraj, Khouri, Issa F., Im, Jin S., Fayad, Luis, Jain, Preetesh, Wang, Michael L., Miranda, Roberto N., Vega, Francisco, Medeiros, Jeffrey, Oki, Yasuhiro, Flowers, Christopher R., Neelapu, Sattva S., and Iyer, Swaminathan P.
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- 2022
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5. MYC/BCL2/BCL6triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2and MYC/BCL6double hit lymphomas
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Huang, Wenting, Medeiros, L., Lin, Pei, Wang, Wei, Tang, Guilin, Khoury, Joseph, Konoplev, Sergej, Yin, C., Xu, Jie, Oki, Yasuhiro, and Li, Shaoying
- Abstract
High-grade B-cell lymphomas with MYC, BCL2, and BCL6rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2double hit lymphoma and 13 patients with MYC/BCL6double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34−85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2and MYC/BCL6double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6double hit lymphoma (p< 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p= 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p= 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.
- Published
- 2018
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6. MYC/BCL2/BCL6triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2and MYC/BCL6double hit lymphomas
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Huang, Wenting, Medeiros, L.Jeffrey, Lin, Pei, Wang, Wei, Tang, Guilin, Khoury, Joseph, Konoplev, Sergej, Yin, C.Cameron, Xu, Jie, Oki, Yasuhiro, and Li, Shaoying
- Abstract
High-grade B-cell lymphomas with MYC, BCL2, and BCL6rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2double hit lymphoma and 13 patients with MYC/BCL6double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34−85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2and MYC/BCL6double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6double hit lymphoma (p< 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p= 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p= 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.
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- 2018
- Full Text
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7. Positron emission tomography–computed tomography predictors of progression after DA-R-EPOCH for PMBCL
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Pinnix, Chelsea C., Ng, Andrea K., Dabaja, Bouthaina S., Milgrom, Sarah A., Gunther, Jillian R., Fuller, C. David, Smith, Grace L., Abou Yehia, Zeinab, Qiao, Wei, Wogan, Christine F., Akhtari, Mani, Mawlawi, Osama, Medeiros, L. Jeffrey, Chuang, Hubert H., Martin-Doyle, William, Armand, Philippe, LaCasce, Ann S., Oki, Yasuhiro, Fanale, Michelle, Westin, Jason, Neelapu, Sattva, and Nastoupil, Loretta
- Abstract
Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18F]fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning–derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance (P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis (P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression.
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- 2018
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8. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma
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Horwitz, Steven M., Koch, Raphael, Porcu, Pierluigi, Oki, Yasuhiro, Moskowitz, Alison, Perez, Megan, Myskowski, Patricia, Officer, Adam, Jaffe, Jacob D., Morrow, Sara N., Allen, Kerstin, Douglas, Mark, Stern, Howard, Sweeney, Jennifer, Kelly, Patrick, Kelly, Virginia, Aster, Jon C., Weaver, David, Foss, Francine M., and Weinstock, David M.
- Abstract
Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)–δ/γ isoforms currently in clinical development. PI3K-δ/γ inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma. Inhibition of either isoform may also contribute to clinical responses by modulating nonmalignant immune cells. We investigated these dual effects in a TCL cohort from a phase 1, open-label study of duvelisib in patients with relapsed or refractory PTCL (n = 16) and CTCL (n = 19), along with in vitro and in vivo models of TCL. The overall response rates in patients with PTCL and CTCL were 50.0% and 31.6%, respectively (P = .32). There were 3 complete responses, all among patients with PTCL. Activity was seen across a wide spectrum of subtypes. The most frequently observed grade 3 and 4 adverse events were transaminase increases (40% alanine aminotransferase, 17% aspartate aminotransferase), maculopapular rash (17%), and neutropenia (17%). Responders and nonresponders had markedly different changes in serum cytokine profiles induced by duvelisib. In vitro, duvelisib potently killed 3 of 4 TCL lines with constitutive phospho-AKT (pAKT) vs 0 of 7 lines lacking pAKT (P = .024) and exceeded cell killing by the PI3K-δ–specific inhibitor idelalisib. Administration of duvelisib to mice engrafted with a PTCL patient-derived xenograft resulted in a shift among tumor-associated macrophages from the immunosuppressive M2-like phenotype to the inflammatory M1-like phenotype. In summary, duvelisib demonstrated promising clinical activity and an acceptable safety profile in relapsed/refractory TCL, as well as preclinical evidence of both tumor cell–autonomous and immune-mediated effects. This trial was registered at www.clinicaltrials.gov as #NCT01476657.
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- 2018
- Full Text
- View/download PDF
9. Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies
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Flinn, Ian W., O’Brien, Susan, Kahl, Brad, Patel, Manish, Oki, Yasuhiro, Foss, Francine F., Porcu, Pierluigi, Jones, Jeffrey, Burger, Jan A., Jain, Nitin, Kelly, Virginia M., Allen, Kerstin, Douglas, Mark, Sweeney, Jennifer, Kelly, Patrick, and Horwitz, Steven
- Abstract
Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-δ (PI3K-δ) and PI3K-γ in late-stage clinical development for hematologic malignancy treatment. This phase 1 study evaluated maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics (PD), efficacy, and safety of duvelisib in 210 patients with advanced hematologic malignancies. In the dose escalation phase (n = 31), duvelisib 8 to 100 mg twice daily was administered, with MTD determined as 75 mg twice daily. In the expansion phase (n = 179), patients with indolent non-Hodgkin lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or T-cell lymphoma (TCL) were treated with 25 or 75 mg duvelisib twice daily continuously. Single-dose duvelisib was rapidly absorbed (time to maximum concentration, 1-2 hours), with a half-life of 5.2 to 10.9 hours. PD results showed inhibition of phospho-AKT (S473) in CLL tumor cells following a single dose and near-complete inhibition of CLL proliferation (Ki-67) by cycle 2. Clinical responses were seen across a range of doses and disease subtypes: iNHL overall response rate, 58% (n = 31) with 6 complete responses (CRs); relapsed/refractory CLL, 56% (n = 55) with 1 CR; peripheral TCL, 50% (n = 16) with 3 CR; and cutaneous TCL, 32% (n = 19). Median time to response was ∼1.8 months. Severe (grade ≥3) adverse events occurred in 84% of patients: neutropenia (32%), alanine transaminase increase (20%), aspartate transaminase increase (15%), anemia and thrombocytopenia (each 14%), diarrhea (11%), and pneumonia (10%). These data support further investigation of duvelisib in phase 2 and 3 studies. This trial was registered at clinicaltrials.gov as #NCT01476657.
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- 2018
- Full Text
- View/download PDF
10. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma
- Author
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Horwitz, Steven M., Koch, Raphael, Porcu, Pierluigi, Oki, Yasuhiro, Moskowitz, Alison, Perez, Megan, Myskowski, Patricia, Officer, Adam, Jaffe, Jacob D., Morrow, Sara N., Allen, Kerstin, Douglas, Mark, Stern, Howard, Sweeney, Jennifer, Kelly, Patrick, Kelly, Virginia, Aster, Jon C., Weaver, David, Foss, Francine M., and Weinstock, David M.
- Abstract
Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)–δ/γ isoforms currently in clinical development. PI3K-δ/γ inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma. Inhibition of either isoform may also contribute to clinical responses by modulating nonmalignant immune cells. We investigated these dual effects in a TCL cohort from a phase 1, open-label study of duvelisib in patients with relapsed or refractory PTCL (n = 16) and CTCL (n = 19), along with in vitro and in vivo models of TCL. The overall response rates in patients with PTCL and CTCL were 50.0% and 31.6%, respectively (P= .32). There were 3 complete responses, all among patients with PTCL. Activity was seen across a wide spectrum of subtypes. The most frequently observed grade 3 and 4 adverse events were transaminase increases (40% alanine aminotransferase, 17% aspartate aminotransferase), maculopapular rash (17%), and neutropenia (17%). Responders and nonresponders had markedly different changes in serum cytokine profiles induced by duvelisib. In vitro, duvelisib potently killed 3 of 4 TCL lines with constitutive phospho-AKT (pAKT) vs 0 of 7 lines lacking pAKT (P= .024) and exceeded cell killing by the PI3K-δ–specific inhibitor idelalisib. Administration of duvelisib to mice engrafted with a PTCL patient-derived xenograft resulted in a shift among tumor-associated macrophages from the immunosuppressive M2-like phenotype to the inflammatory M1-like phenotype. In summary, duvelisib demonstrated promising clinical activity and an acceptable safety profile in relapsed/refractory TCL, as well as preclinical evidence of both tumor cell–autonomous and immune-mediated effects. This trial was registered at www.clinicaltrials.govas #NCT01476657.
- Published
- 2018
- Full Text
- View/download PDF
11. Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies
- Author
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Flinn, Ian W., O'Brien, Susan, Kahl, Brad, Patel, Manish, Oki, Yasuhiro, Foss, Francine F., Porcu, Pierluigi, Jones, Jeffrey, Burger, Jan A., Jain, Nitin, Kelly, Virginia M., Allen, Kerstin, Douglas, Mark, Sweeney, Jennifer, Kelly, Patrick, and Horwitz, Steven
- Abstract
Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-δ (PI3K-δ) and PI3K-γ in late-stage clinical development for hematologic malignancy treatment. This phase 1 study evaluated maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics (PD), efficacy, and safety of duvelisib in 210 patients with advanced hematologic malignancies. In the dose escalation phase (n = 31), duvelisib 8 to 100 mg twice daily was administered, with MTD determined as 75 mg twice daily. In the expansion phase (n = 179), patients with indolent non-Hodgkin lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or T-cell lymphoma (TCL) were treated with 25 or 75 mg duvelisib twice daily continuously. Single-dose duvelisib was rapidly absorbed (time to maximum concentration, 1-2 hours), with a half-life of 5.2 to 10.9 hours. PD results showed inhibition of phospho-AKT (S473) in CLL tumor cells following a single dose and near-complete inhibition of CLL proliferation (Ki-67) by cycle 2. Clinical responses were seen across a range of doses and disease subtypes: iNHL overall response rate, 58% (n = 31) with 6 complete responses (CRs); relapsed/refractory CLL, 56% (n = 55) with 1 CR; peripheral TCL, 50% (n = 16) with 3 CR; and cutaneous TCL, 32% (n = 19). Median time to response was ∼1.8 months. Severe (grade ≥3) adverse events occurred in 84% of patients: neutropenia (32%), alanine transaminase increase (20%), aspartate transaminase increase (15%), anemia and thrombocytopenia (each 14%), diarrhea (11%), and pneumonia (10%). These data support further investigation of duvelisib in phase 2 and 3 studies. This trial was registered at clinicaltrials.govas #NCT01476657.
- Published
- 2018
- Full Text
- View/download PDF
12. Reclassifying patients with early-stage Hodgkin lymphoma based on functional radiographic markers at presentation
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Akhtari, Mani, Milgrom, Sarah A., Pinnix, Chelsea C., Reddy, Jay P., Dong, Wenli, Smith, Grace L., Mawlawi, Osama, Abou Yehia, Zeinab, Gunther, Jillian, Osborne, Eleanor M., Andraos, Therese Y., Wogan, Christine F., Rohren, Eric, Garg, Naveen, Chuang, Hubert, Khoury, Joseph D., Oki, Yasuhiro, Fanale, Michelle, and Dabaja, Bouthaina S.
- Abstract
The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient’s risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTVt and TLGt were highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients.
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- 2018
- Full Text
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13. Reclassifying patients with early-stage Hodgkin lymphoma based on functional radiographic markers at presentation
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Akhtari, Mani, Milgrom, Sarah A., Pinnix, Chelsea C., Reddy, Jay P., Dong, Wenli, Smith, Grace L., Mawlawi, Osama, Abou Yehia, Zeinab, Gunther, Jillian, Osborne, Eleanor M., Andraos, Therese Y., Wogan, Christine F., Rohren, Eric, Garg, Naveen, Chuang, Hubert, Khoury, Joseph D., Oki, Yasuhiro, Fanale, Michelle, and Dabaja, Bouthaina S.
- Abstract
The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient's risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTVtand TLGtwere highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients.
- Published
- 2018
- Full Text
- View/download PDF
14. Encouraging activity for R-CHOP in advanced stage nodular lymphocyte–predominant Hodgkin lymphoma
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Fanale, Michelle A., Cheah, Chan Yoon, Rich, Amy, Medeiros, L.Jeffrey, Lai, Chao-Ming, Oki, Yasuhiro, Romaguera, Jorge E., Fayad, Luis E., Hagemeister, F.B., Samaniego, Felipe, Rodriguez, Maria A., Neelapu, Sattva S., Lee, Hun J., Nastoupil, Loretta, Fowler, Nathan H., Turturro, Francesco, Westin, Jason R., Wang, Michael L., McLaughlin, Peter, Pinnix, Chelsea C., Milgrom, Sarah A., Dabaja, Bouthaina, Horowitz, Sandra B., and Younes, Anas
- Abstract
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P= .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P= .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.
- Published
- 2017
- Full Text
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15. Encouraging activity for R-CHOP in advanced stage nodular lymphocyte–predominant Hodgkin lymphoma
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Fanale, Michelle A., Cheah, Chan Yoon, Rich, Amy, Medeiros, L. Jeffrey, Lai, Chao-Ming, Oki, Yasuhiro, Romaguera, Jorge E., Fayad, Luis E., Hagemeister, F. B., Samaniego, Felipe, Rodriguez, Maria A., Neelapu, Sattva S., Lee, Hun J., Nastoupil, Loretta, Fowler, Nathan H., Turturro, Francesco, Westin, Jason R., Wang, Michael L., McLaughlin, Peter, Pinnix, Chelsea C., Milgrom, Sarah A., Dabaja, Bouthaina, Horowitz, Sandra B., and Younes, Anas
- Abstract
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.
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- 2017
- Full Text
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16. P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma
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Wang, Xuan J, Jeffrey Medeiros, L, Bueso-Ramos, Carlos E, Tang, Guilin, Wang, Sa, Oki, Yasuhiro, Desai, Parth, Khoury, Joseph D, Miranda, Roberto N, Tang, Zhenya, Reddy, Nishitha, and Li, Shaoying
- Abstract
In patients with diffuse large B-cell lymphoma, MYCrearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novodiffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53. Compared with patients with P53 negative lymphoma, the P53 positive group had a poorer overall survival (P=0.004). In patients with lymphoma harboring MYC-R, MYC expression or MYC+/BCL2+, P53 expression was associated with a significantly worse overall survival (P<0.0001, P=0.01, and P=0.035, respectively). Patients with lymphoma showing concurrent P53 expression and MYC-R had a worse prognosis compared with patients with either P53 expression or MYC-R alone (P<0.0001). Similarly, P53 enhanced the negative prognostic effect of MYC expression in DLBCL patients. In addition, among patients with lymphoma with concurrent MYC and P53 expression, MYC and BCL2 or BCL2 & P53 expression, those patients with tumors with MYC and P53 expression had the worst overall survival (P=0.005), regardless of BCL2 expression status. Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC-R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novodiffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.
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- 2017
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17. P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma
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Wang, Xuan J, Jeffrey Medeiros, L, Bueso-Ramos, Carlos E, Tang, Guilin, Wang, Sa, Oki, Yasuhiro, Desai, Parth, Khoury, Joseph D, Miranda, Roberto N, Tang, Zhenya, Reddy, Nishitha, and Li, Shaoying
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In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53. Compared with patients with P53 negative lymphoma, the P53 positive group had a poorer overall survival (P=0.004). In patients with lymphoma harboring MYC-R, MYC expression or MYC+/BCL2+, P53 expression was associated with a significantly worse overall survival (P<0.0001, P=0.01, and P=0.035, respectively). Patients with lymphoma showing concurrent P53 expression and MYC-R had a worse prognosis compared with patients with either P53 expression or MYC-R alone (P<0.0001). Similarly, P53 enhanced the negative prognostic effect of MYC expression in DLBCL patients. In addition, among patients with lymphoma with concurrent MYC and P53 expression, MYC and BCL2 or BCL2 & P53 expression, those patients with tumors with MYC and P53 expression had the worst overall survival (P=0.005), regardless of BCL2 expression status. Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC -R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novo diffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.
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- 2017
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18. A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL
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Cherng, Hua-Jay J., Alig, Stefan K., Oki, Yasuhiro, Nastoupil, Loretta J., Fayad, Luis, Neelapu, Sattva S., Turturro, Francesco, Hagemeister, Fredrick, Craig, Alexander F.M., Macaulay, Charles W., Rodriguez, Maria Alma, Lee, Hun Ju, McDonnell, Timothy J., Flowers, Christopher R., Vega, Francisco, Green, Michael R., Feng, Lei, Kurtz, David M., Alizadeh, Ash A., Davis, R. Eric, and Westin, Jason R.
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•Lenalidomide, obintuzumab, and CHOP chemotherapy are efficacious and well tolerated treatments for newly diagnosed DLBCL.•LO-CHOP led to high molecular response rates based on circulating tumor DNA sequencing during and after treatment in this phase 1b/2 study.
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- 2023
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19. Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy
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Pinnix, Chelsea C., Osborne, Eleanor M., Chihara, Dai, Lai, Peter, Zhou, Shouhao, Ramirez, Mildred M., Oki, Yasuhiro, Hagemeister, Frederick B., Rodriguez, Alma M., Samaniego, Felipe, Fowler, Nathan, Romaguera, Jorge E., Turturro, Francesco, Fayad, Luis, Westin, Jason R., Nastoupil, Loretta, Neelapu, Sattva S., Cheah, Chan Y., Dabaja, Bouthaina S., Milgrom, Sarah A., Smith, Grace L., Horace, Patricia, Milbourne, Andrea, Wogan, Christine F., Ballas, Leslie, and Fanale, Michelle A.
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IMPORTANCE: The management of lymphoma diagnosed during pregnancy is controversial and has been guided largely by findings from case reports and small series. OBJECTIVE: To determine maternal and fetal outcomes of women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis studied a cohort of 39 pregnant women diagnosed with HL and NHL (31 HL and 8 NHL) at a single specialized cancer institution between January 1991 and December 2014. MAIN OUTCOMES AND MEASURES: We examined data on disease and treatment characteristics, as well as maternal and fetal complications and outcomes. The Kaplan-Meier method was used to compare progression free survival (PFS) and overall survival (OS) according to receipt of antenatal therapy and other clinical factors. Univariate and multivariate analyses were performed by using Cox proportional hazard regression models to identify potential associations between clinical and treatment factors and survival. RESULTS: The median (range) age of the 39 women in the patient cohort was 28 (19-38) years; 32 women (82%) had stage I or II disease at diagnosis, and 13 had bulky disease. Three women electively terminated the pregnancy to allow immediate systemic therapy; of the remaining 36 women, 24 received antenatal therapy (doxorubicin based combination chemotherapy in 20 of 24 patients), and 12 deferred therapy until after delivery. Four women experienced miscarriage, all of whom had received antenatal systemic therapy and 2 during the first trimester. Delivery occurred at a median (range) of 37 (32-42) weeks and was no different based on receipt of antenatal (median [range], 37 [33-42] weeks) vs postnatal (median [range], 37 [32-42] weeks) therapy (P = .21). No gross fetal malformations or anomalies were detected. At a median (range) follow-up time of 67.9 (8.8-277.5) months since the diagnosis of lymphoma, 5-year rates of PFS and OS were 74.7% and 82.4%, respectively; these rates did not differ according to timing of therapy. On univariate analysis, bulky disease (>10 cm), extranodal nonbone marrow involvement, and poor performance status (Eastern Cooperative Oncology Group score, ≥2) predicted increased risk of disease progression. On multivariate analysis, extranodal nonbone marrow disease and performance status remained significant for both PFS and OS. CONCLUSIONS AND RELEVANCE: Systemic therapy given for lymphoma after the first trimester of pregnancy is likely safe and results in acceptable maternal and fetal outcomes.
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- 2016
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20. Prognostic Factors of Hepatosplenic T-cell Lymphoma
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Yabe, Mariko, Medeiros, L. Jeffrey, Tang, Guilin, Wang, Sa A., Ahmed, Sairah, Nieto, Yago, Hu, Shimin, Bhagat, Govind, Oki, Yasuhiro, Patel, Keyur P., Routbort, Mark, Luthra, Rajyalakshmi, Fanale, Michelle A., Bueso-Ramos, Carlos E., Jorgensen, Jeffrey L., Vega, Francisco, Chen, Weina, Hoehn, Daniela, Konoplev, Sergej, Milton, Denai R., Wistuba, Ignacio, Li, Shaoying, You, M. James, Young, Ken H., and Miranda, Roberto N.
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Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αβ TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αβ TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, αβ TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL.
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- 2016
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21. Spatial effects of oxovanadium-immobilized mesoporous silica on racemization of alcohols and application in lipase-catalyzed dynamic kinetic resolutionElectronic supplementary information (ESI) available: Details of experimental procedures, characterization for V-MPS and NMR spectra of compounds. See DOI: 10.1039/c6cy00257a
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Sugiyama, Koji, Oki, Yasuhiro, Kawanishi, Shinji, Kato, Katsuya, Ikawa, Takashi, Egi, Masahiro, and Akai, Shuji
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We recently reported a new dynamic kinetic resolution (DKR) method based on the combination of lipase-catalyzed kinetic resolution of racemic alcohols and the V-MPS3-catalyzed in situracemization of less reactive alcohol enantiomers. In V-MPS3, oxovanadium moieties were covalently bound to the inner surface of mesoporous silica (MPS) with a pore size of about 3 nm. The catalytic activity of V-MPS3 was much higher than that of related vanadium compounds; however, we could neither explain its unusually high activity nor confirm that the racemization predominantly occurred inside the V-MPS pores. Therefore, in this study, we prepared V-MPS2 and V-MPS4 from the corresponding MPS with pore diameters of approximately 2 nm and 4 nm, respectively and compared their racemization activities with that of V-MPS3 using some optically active alcohols with different molecular sizes and polarities. We discovered a positive correlation between the pore size of V-MPS and substrate racemization rate as well as the high polarity of the MPS pores. The results suggested that the racemization predominantly occurs in the pores of V-MPS and that a small pore size (2–4 nm) is essential to generate the polar environment of V-MPS, which probably accelerates the racemization by facilitating the C–O bond cleavage of the vanadate intermediates. Using V-MPS with a pore size suitable for each substrate, lipase/oxovanadium combo-catalyzed DKR could be applied to a wider range of alcohols including allyl alcohols, benzylic alcohols, and propargyl alcohols to give the corresponding esters in excellent isolated yields and enantioselectivities.
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- 2016
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22. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression
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Jacobsen, Eric D., Sharman, Jeff P., Oki, Yasuhiro, Advani, Ranjana H., Winter, Jane N., Bello, Celeste M., Spitzer, Gary, Palanca-Wessels, Maria Corinna, Kennedy, Dana A., Levine, Pamela, Yang, Jing, and Bartlett, Nancy L.
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Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30+ NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.
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- 2015
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23. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression
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Jacobsen, Eric D., Sharman, Jeff P., Oki, Yasuhiro, Advani, Ranjana H., Winter, Jane N., Bello, Celeste M., Spitzer, Gary, Palanca-Wessels, Maria Corinna, Kennedy, Dana A., Levine, Pamela, Yang, Jing, and Bartlett, Nancy L.
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Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30+NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.govas #NCT01421667.
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- 2015
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24. Phase II study of yttrium-90-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma.
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Wang M, Oki Y, Pro B, Romaguera JE, Rodriguez MA, Samaniego F, McLaughlin P, Hagemeister F, Neelapu S, Copeland A, Samuels BI, Loyer EM, Ji Y, Younes A, Wang, Michael, Oki, Yasuhiro, Pro, Barbara, Romaguera, Jorge Enrique, Rodriguez, Maria Alma, and Samaniego, Felipe
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- 2009
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25. Brentuximab vedotinfor treatment of systemic T-cell lymphoma
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Chihara, Dai and Oki, Yasuhiro
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Introduction:Brentuximab vedotin(BV) is an antibody-drug conjugate that consists of the anti-CD30 monoclonal antibody conjugated with monomethyl auristatin E. BV has been approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsed or refractory Hodgkin lymphoma and anaplastic large cell lymphoma. These two diseases certainly show high levels of CD30 expression. Of interest, however, BV has shown activities in other lymphomas that express low or even undetectable levels of CD30.Areas covered:We update and summarize a recent report of BV in T-cell lymphomas.Expert opinion:Single-agent BV showed overall response rates of 54% in angioimmunoblastic T-cell lymphoma and 33% in peripheral T-cell lymphoma not otherwise specified in the recent trial. The efficacy of BV in T-cell lymphomas with low or undetectable CD30 expression was promising. The use of BV in combination with chemotherapy as frontline treatment is currently being investigated. Future studies should include correlative biomarker analysis and optimization of combination therapies.
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- 2014
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26. Use of panobinostat in patients with classical Hodgkin lymphoma
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Oki, Yasuhiro
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SUMMARY Panobinostat is a deacetylase inhibitor that exerts antitumor activity by modifying the acetylation status of histones and other critical cellular proteins. Panobinostat as a single agent produced an overall response rate of 27 in patients with relapsed or recurrent Hodgkin lymphoma after stem cell transplantation. Clinical trials of panobinostat combined with chemotherapy or with other targeting agents such as mTOR inhibitors or lenalidomide have shown promising interim results. The most common toxicity with panobinostat as a single agent or in combination is thrombocytopenia. Patient enrollment in ongoing or future clinical trials of panobinostat is encouraged so that the role of this agent in patients with recurrent classical Hodgkin lymphoma can be further studied.
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- 2014
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27. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin
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Horwitz, Steven M., Advani, Ranjana H., Bartlett, Nancy L., Jacobsen, Eric D., Sharman, Jeff P., O'Connor, Owen A., Siddiqi, Tanya, Kennedy, Dana A., and Oki, Yasuhiro
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This phase 2, open-label, multicenter study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, in relapsed/refractory CD30+non-Hodgkin lymphomas. The primary end point was objective response rate (ORR). Key secondary end points included safety, correlation of CD30 expression with response, response duration, and progression-free survival (PFS). Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks until progression or unacceptable toxicity. This planned subset analysis included patients with peripheral T-cell lymphomas (PTCLs; n = 35), specifically angioimmunoblastic T-cell lymphoma (AITL; n = 13) and PTCL not otherwise specified (n = 22). Median age was 64 years; 63% were refractory to most recent therapy. Of 34 evaluable patients, ORR was 41% (8 complete remissions [CRs], 6 partial remissions [PRs]), and ORR was 54% in AITL (5 CRs, 2 PRs) with median PFS of 6.7 months thus far. No correlation between CD30 expression per central review and response was observed. Safety data were consistent with the known profile of brentuximab vedotin, and included at least grade 3 events of neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each). In summary, brentuximab vedotin showed antitumor activity in patients with relapsed PTCL particularly AITL. This trial was registered at www.clinicaltrials.govas #NCT01421667.
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- 2014
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28. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin
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Horwitz, Steven M., Advani, Ranjana H., Bartlett, Nancy L., Jacobsen, Eric D., Sharman, Jeff P., O’Connor, Owen A., Siddiqi, Tanya, Kennedy, Dana A., and Oki, Yasuhiro
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This phase 2, open-label, multicenter study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, in relapsed/refractory CD30+ non-Hodgkin lymphomas. The primary end point was objective response rate (ORR). Key secondary end points included safety, correlation of CD30 expression with response, response duration, and progression-free survival (PFS). Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks until progression or unacceptable toxicity. This planned subset analysis included patients with peripheral T-cell lymphomas (PTCLs; n = 35), specifically angioimmunoblastic T-cell lymphoma (AITL; n = 13) and PTCL not otherwise specified (n = 22). Median age was 64 years; 63% were refractory to most recent therapy. Of 34 evaluable patients, ORR was 41% (8 complete remissions [CRs], 6 partial remissions [PRs]), and ORR was 54% in AITL (5 CRs, 2 PRs) with median PFS of 6.7 months thus far. No correlation between CD30 expression per central review and response was observed. Safety data were consistent with the known profile of brentuximab vedotin, and included at least grade 3 events of neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each). In summary, brentuximab vedotin showed antitumor activity in patients with relapsed PTCL particularly AITL. This trial was registered at www.clinicaltrials.gov as #NCT01421667.
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- 2014
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29. Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma
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Younes, Anas, Oki, Yasuhiro, McLaughlin, Peter, Copeland, Amanda R., Goy, Andre, Pro, Barbara, Feng, Lei, Yuan, Ying, Chuang, Hubert H., Macapinlac, Homer A., Hagemeister, Fredrick, Romaguera, Jorge, Samaniego, Felipe, Fanale, Michelle A., Dabaja, Bouthaina Shbib, Rodriguez, Maria A., Dang, Nam, Kwak, Larry W., Neelapu, Sattva S., and Fayad, Luis E.
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In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m2 weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHLwas 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial. This trial has been completed and is registered with www.clinicaltrials.gov as NCT00504504.
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- 2012
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30. Brentuximab vedotinin systemic T-cell lymphoma
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Oki, Yasuhiro and Younes, Anas
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Introduction:Brentuximab vedotinis an antibody–drug conjugate which consists of the anti-CD30 monoclonal antibody cAC10 conjugated with the cytotoxic agent monomethyl auristatin E (MMAE). Brentuximab vedotin has been approved by the US Food and Drug Administration for the treatment of relapsed or refractory Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL). The efficacy of brentuximab vedotin in other CD30+lymphomas is currently being investigated.Areas covered:In this paper, we review the currently available treatment options for systemic peripheral T-cell lymphomas (PTCL) and the role of brentuximab vedotin in relapsed or refractory ALCL. In addition, ongoing clinical trial of brentuximab vedotin in relapsed PTCL and combination therapy with other chemotherapies for initial treatment of CD30 lymphoma will also be reviewed.Expert opinion:Brentuximab vedotin has established its role in the treatment of relapsed or refractory HL and ALCL. In the next few years, the efficacy of this agent in other CD30+lymphomas will be described. The safety and efficacy of several brentuximab-based combination regimens, including use as frontline chemotherapy is under investigation.
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- 2012
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31. Favorable Consolidative Effect of High-Dose Melphalan and Total-Body Irradiation Followed by Autologous Peripheral Blood Stem Cell Transplantation After Rituximab-Containing Induction Chemotherapy With In Vivo Purging in Relapsed or Refractory Follicular Lymphoma
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Kato, Harumi, Taji, Hirofumi, Ogura, Michinori, Kagami, Yoshitoyo, Oki, Yasuhiro, Tsujimura, Akane, Fuwa, Nobukazu, Kodaira, Takeshi, Seto, Masao, Yamamoto, Kazuhito, and Morishima, Yasuo
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In this study, we sought to evaluate the efficacy and toxicity of high-dose therapy followed by autologous peripheral blood stem cell transplantation (autoPBSCT) after rituximab-containing induction chemotherapy with in vivo purging for relapsed or refractory chemosensitive advanced-stage follicular lymphoma (FL).
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- 2009
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32. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia
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Kantarjian, Hagop, Oki, Yasuhiro, Garcia-Manero, Guillermo, Huang, Xuelin, O'Brien, Susan, Cortes, Jorge, Faderl, Stefan, Bueso-Ramos, Carlos, Ravandi, Farhad, Estrov, Zeev, Ferrajoli, Alessandra, Wierda, William, Shan, Jianqin, Davis, Jan, Giles, Francis, Saba, Hussain I., and Issa, Jean-Pierre J.
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Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2 subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P < .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS.
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- 2007
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33. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia
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Kantarjian, Hagop, Oki, Yasuhiro, Garcia-Manero, Guillermo, Huang, Xuelin, O'Brien, Susan, Cortes, Jorge, Faderl, Stefan, Bueso-Ramos, Carlos, Ravandi, Farhad, Estrov, Zeev, Ferrajoli, Alessandra, Wierda, William, Shan, Jianqin, Davis, Jan, Giles, Francis, Saba, Hussain I., and Issa, Jean-Pierre J.
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Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2intravenously daily for 5 days; (2) 20 mg/m2subcutaneously daily for 5 days; and (3) 10 mg/m2intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P< .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS.
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- 2007
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34. Review: Recent Clinical Trials in Epigenetic Therapy
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Oki, Yasuhiro and Issa, Jean-Pierre
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Epigenetic factors such as DNA methylation and histone deacetylation are known to contribute to the malignant transformation of cells by silencing critical genes. Drugs that inhibit DNA methyltransferases or histone deacetylases were shown to have the potential to reactivate silenced genes and induce differentiation or apoptosis of malignant cells. The most intensively studied class of such agents is DNA methyltransferase inhibitors, including 5-azacytidine (azacitidine) and 5-aza-2-deoxycytidine (decitabine). In 2004, azacitidine was approved for the treatment of myelodysplastic syndrome on the basis of phase II and III studies that showed a response rate (complete and partial responses) of 15. Azacitidine is also being evaluated in clinical trials for other malignant diseases. Decitabine has response rates of 17-49 in myelodysplastic syndrome in multiple phase II and III studies and also activity in acute and chronic myelogenous leukemia. Histone deacetylase inhibitors belong to another class of epigenetic modifying agents that include depsipeptide, butyrate derivatives, suberoylanilide hydroxamic acid and valproic acid. No agent in this class has been studied in a phase III trial, but several agents have been or are being studied in phase II trials. Further research is needed to determine the appropriate patient selection and dosing schedules.
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- 2006
35. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center
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Oki, Yasuhiro, Kantarjian, Hagop M., Zhou, Xian, Cortes, Jorge, Faderl, Stefan, Verstovsek, Srdan, O'Brien, Susan, Koller, Charles, Beran, Miloslav, Bekele, B. Nebiyou, Pierce, Sherry, Thomas, Deborah, Ravandi, Farhad, Wierda, William G., Giles, Francis, Ferrajoli, Alessandra, Jabbour, Elias, Keating, Michael J., Bueso-Ramos, Carlos E., Estey, Elihu, and Garcia-Manero, Guillermo
- Abstract
To characterize acute megakaryocytic leukemia (FAB M7 AML), we identified 37 patients with M7 AML treated at M.D. Anderson Cancer Center between 1987 and 2003 and compared them with 1800 patients with non-M7, non-M3 AML treated during the same period. The median age of the M7 AML group was 56 years (range, 21-78 years); 22 patients (59%) had an antecedent hematologic disorder or myelodysplastic syndrome or both, and 7 patients (19%) had previously received chemotherapy for other malignancies. Extensive bone marrow fibrosis was found in 23 patients (62%). Poor cytogenetic characteristics were observed in 49% of patients with M7 AML versus 33% of others (P< .001). Complete remission rates were 43% with M7 AML and 57% with non-M7 AML (P= .089). Median overall survival (OS) was 23 and 38 weeks, respectively (P= .006). Median disease-free survivals were 23 versus 52 weeks, respectively (P< .001). By multivariate analysis, M7 AML was an independent adverse prognostic factor for OS, independent of other factors including cytogenetic abnormalities (hazard ratio 1.51, P= .049). These results confirm the poor prognosis of M7 AML and indicate that other biologic characteristics beyond cytogenetic abnormalities likely play a role in this disease.
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- 2006
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36. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center
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Oki, Yasuhiro, Kantarjian, Hagop M., Zhou, Xian, Cortes, Jorge, Faderl, Stefan, Verstovsek, Srdan, O'Brien, Susan, Koller, Charles, Beran, Miloslav, Bekele, B. Nebiyou, Pierce, Sherry, Thomas, Deborah, Ravandi, Farhad, Wierda, William G., Giles, Francis, Ferrajoli, Alessandra, Jabbour, Elias, Keating, Michael J., Bueso-Ramos, Carlos E., Estey, Elihu, and Garcia-Manero, Guillermo
- Abstract
To characterize acute megakaryocytic leukemia (FAB M7 AML), we identified 37 patients with M7 AML treated at M.D. Anderson Cancer Center between 1987 and 2003 and compared them with 1800 patients with non-M7, non-M3 AML treated during the same period. The median age of the M7 AML group was 56 years (range, 21-78 years); 22 patients (59%) had an antecedent hematologic disorder or myelodysplastic syndrome or both, and 7 patients (19%) had previously received chemotherapy for other malignancies. Extensive bone marrow fibrosis was found in 23 patients (62%). Poor cytogenetic characteristics were observed in 49% of patients with M7 AML versus 33% of others (P < .001). Complete remission rates were 43% with M7 AML and 57% with non-M7 AML (P = .089). Median overall survival (OS) was 23 and 38 weeks, respectively (P = .006). Median disease-free survivals were 23 versus 52 weeks, respectively (P < .001). By multivariate analysis, M7 AML was an independent adverse prognostic factor for OS, independent of other factors including cytogenetic abnormalities (hazard ratio 1.51, P = .049). These results confirm the poor prognosis of M7 AML and indicate that other biologic characteristics beyond cytogenetic abnormalities likely play a role in this disease.
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- 2006
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37. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome–negative CML, and megakaryocytic leukemia
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Jelinek, Jaroslav, Oki, Yasuhiro, Gharibyan, Vazganush, Bueso-Ramos, Carlos, Prchal, Josef T., Verstovsek, Srdan, Beran, Miloslav, Estey, Elihu, Kantarjian, Hagop M., and Issa, Jean-Pierre J.
- Abstract
An activating 1849G>T mutation of JAK2 (Janus kinase 2) tyrosine kinase was recently described in chronic myeloproliferative disorders (MPDs). Its role in other hematologic neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematologic neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5 [36%] of 14 patients). JAK2 mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)–negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes. No mutation was found in Ph+CML (99 patients), AML M0-M6 (28 patients), or acute lymphoblastic leukemia (20 patients). We conclude that the JAK2 1849G>T mutation is common in Ph– MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.
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- 2005
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38. JAK2mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome–negative CML, and megakaryocytic leukemia
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Jelinek, Jaroslav, Oki, Yasuhiro, Gharibyan, Vazganush, Bueso-Ramos, Carlos, Prchal, Josef T., Verstovsek, Srdan, Beran, Miloslav, Estey, Elihu, Kantarjian, Hagop M., and Issa, Jean-Pierre J.
- Abstract
An activating 1849G>T mutation of JAK2 (Janus kinase 2) tyrosine kinase was recently described in chronic myeloproliferative disorders (MPDs). Its role in other hematologic neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematologic neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5 [36%] of 14 patients). JAK2mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)–negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes. No mutation was found in Ph+CML (99 patients), AML M0-M6 (28 patients), or acute lymphoblastic leukemia (20 patients). We conclude that the JAK21849G>T mutation is common in Ph–MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.
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- 2005
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39. Phase II study of oxaliplatin in patients with recurrent or refractory non‐Hodgkin lymphoma
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Oki, Yasuhiro, McLaughlin, Peter, Pro, Barbara, Hagemeister, Fredrick B., Bleyer, Archie, Loyer, Evelyn, and Younes, Anas
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Oxaliplatin is a platinum derivative with a broad range of anticancer activity. The objective of the current Phase II trial was to investigate the activity of oxaliplatin in patients with recurrent or refractory non‐Hodgkin lymphoma (NHL).Patients with recurrent and refractory NHL who received a maximum of 3 previous chemotherapy regimens were considered eligible if they had an Eastern Cooperative Oncology Group performance status of 0–2 and adequate organ function. Oxaliplatin was administered in an outpatient setting at a dose of 130 mg/m2 by 2‐hour intravenous infusion every 21 days for ≤ 6 cycles in the absence of disease progression.Thirty‐one patients (23 with aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable for toxicity, response, and survival. The median patient age was 62 years, and 20% of the patients previously received platinum‐containing therapy. Eighty‐three percent of the patients were refractory to their last treatment regimens. Grade 3 and 4 toxic effects (according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence interval, 13–47%) of the patients. Responses were observed in platinum‐naive patients as well as in those previously treated with platinum. The overall median failure‐free survival duration was 3.0 months (range, 0.1–18.1 months).Oxaliplatin had favorable single‐agent activity in previously treated patients with refractory lymphoma. The favorable safety profile and the ease of its administration in outpatient settings warrant investigating it in combination with other active drugs for the treatment of recurrent and refractory NHL. Cancer 2005. © 2005 American Cancer Society.
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- 2005
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40. Heat shock protein-based cancer vaccines
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Oki, Yasuhiro and Younes, Anas
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Heat shock proteins (HSPs) exist ubiquitously across all species and function as chaperones stabilizing and delivering peptides. Tumor-derived HSP–peptide complex has been known to induce immunity against the original tumor in preclinical studies. HSP-based vaccines work across tumor types and bypass the need for identifying the responsible peptide(s) for inducing immunity. These vaccines are tumor- and patient-specific in that they capture the tumor cells’ fingerprints. HSP-based vaccines have been studied in early phase clinical trials, mostly using HSP glycoprotein 96, for various types of malignancies including melanoma, renal cell carcinoma, gastric cancer, pancreatic cancer, low-grade lymphoma, colorectal cancer and chronic myelogenous leukemia. All showed minimal toxicity and potential efficacy. Phase III studies for melanoma and renal cell carcinoma are ongoing. HSP-based vaccines are a novel vaccine preparation with a promising role in cancer management. Further studies to determine the administering strategy and specific indication are warranted.
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- 2004
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41. Lenalidomide, idelalisib, and rituximab are unacceptably toxic in patients with relapsed/refractory indolent lymphoma
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Cheah, Chan Yoon, Nastoupil, Loretta J., Neelapu, Sattva S., Forbes, Sheryl G., Oki, Yasuhiro, and Fowler, Nathan H.
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- 2015
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42. Lenalidomide, idelalisib, and rituximab are unacceptably toxic in patients with relapsed/refractory indolent lymphoma
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Cheah, Chan Yoon, Nastoupil, Loretta J., Neelapu, Sattva S., Forbes, Sheryl G., Oki, Yasuhiro, and Fowler, Nathan H.
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- 2015
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43. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia
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Oki, Yasuhiro, Jelinek, Jaroslav, Shen, Lanlan, Kantarjian, Hagop M., and Issa, Jean-Pierre J.
- Abstract
Decitabine's mechanism of action in chronic myelomonocytic leukemia remains incompletely understood. We studied the dynamics of neoplastic cell clearance during decitabine treatment (100 mg/m2 per course every 4 weeks) using quantitative monitoring of mutant alleles by pyrosequencing. Patients with chronic myelomonocytic leukemia were first screened for JAK2 and NPM1 mutations, and 3 patients with mutations were identified. Mutant allele percentages in mononuclear cell DNA were followed after treatment, along with methylation of LINE1 and 10 other genes. The clearance of mutant alleles was modest after the first cycle, despite induction of hypomethylation. Delayed substantial clearance was observed after 2 to 4 cycles that correlated with clinical response. Two patients had complete disappearance of mutant alleles and sustained clinical remissions. In another patient, mutant allele was detectable at clinical remission, which lasted for 8 months. Our data suggest a predominantly noncytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic clone and/or normal cells. This trial was registered at www.ClinicalTrials.gov as #NCT00067808.
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- 2008
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44. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia
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Oki, Yasuhiro, Jelinek, Jaroslav, Shen, Lanlan, Kantarjian, Hagop M., and Issa, Jean-Pierre J.
- Abstract
Decitabine's mechanism of action in chronic myelomonocytic leukemia remains incompletely understood. We studied the dynamics of neoplastic cell clearance during decitabine treatment (100 mg/m2per course every 4 weeks) using quantitative monitoring of mutant alleles by pyrosequencing. Patients with chronic myelomonocytic leukemia were first screened for JAK2and NPM1mutations, and 3 patients with mutations were identified. Mutant allele percentages in mononuclear cell DNA were followed after treatment, along with methylation of LINE1and 10 other genes. The clearance of mutant alleles was modest after the first cycle, despite induction of hypomethylation. Delayed substantial clearance was observed after 2 to 4 cycles that correlated with clinical response. Two patients had complete disappearance of mutant alleles and sustained clinical remissions. In another patient, mutant allele was detectable at clinical remission, which lasted for 8 months. Our data suggest a predominantly noncytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic clone and/or normal cells. This trial was registered at www.ClinicalTrials.govas #NCT00067808.
- Published
- 2008
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45. Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results
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Westin, Jason R., Nastoupil, Loretta J., Fayad, Luis, Hagemeister, Fredrick B., Oki, Yasuhiro, Turturro, Francesco, Ahmed, Sairah, Rodriguez, Maria Alma, Lee, Hun Ju, Steiner, Raphael Eric, Nair, Ranjit, Parmar, Simrit, Young, Ken H., McDonnell, Timothy J., Chuang, Hubert, Green, Michael R, Neelapu, Sattva S, and Davis, Eric
- Abstract
Westin: Curis: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; Janssen: Other: Advisory Board, Research Funding; Novartis: Other: Advisory Board, Research Funding; Genentech: Other: Advisory Board, Research Funding; 47 Inc: Research Funding; Juno: Other: Advisory Board; Unum: Research Funding; MorphoSys: Other: Advisory Board; Kite: Other: Advisory Board, Research Funding. Nastoupil:Bayer: Honoraria; Celgene: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Spectrum: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Genentech, Inc.: Honoraria, Research Funding. Oki:Jazz: Employment. Parmar:Cellenkos Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chuang:Sage Evidence-based Medicine & Practice Institute: Consultancy. Neelapu:Celgene: Consultancy, Research Funding; Unum Therapeutics: Consultancy, Research Funding; BMS: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Cellectis: Research Funding; Karus: Research Funding; Novartis: Consultancy; Merck: Consultancy, Research Funding; Acerta: Research Funding; Precision Biosciences: Consultancy; Cell Medica: Consultancy; Allogene: Consultancy; Incyte: Consultancy; Poseida: Research Funding; Pfizer: Consultancy.Ibrutinib and lenalidomide are not yet indicated for DLBCL, we will describe our trial
- Published
- 2019
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46. Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results
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Westin, Jason R., Nastoupil, Loretta J., Fayad, Luis, Hagemeister, Fredrick B., Oki, Yasuhiro, Turturro, Francesco, Ahmed, Sairah, Rodriguez, Maria Alma, Lee, Hun Ju, Steiner, Raphael Eric, Nair, Ranjit, Parmar, Simrit, Young, Ken H., McDonnell, Timothy J., Chuang, Hubert, Green, Michael R, Neelapu, Sattva S, and Davis, Eric
- Abstract
Background:Diffuse Large B-cell Lymphoma (DLBCL), the most common lymphoid cancer, is classified by the cell of origin into the germinal and non-germinal center (non-GCB) subtypes. The non-GCB subtype is associated with inferior outcomes with standard therapies, but the BTK inhibitor ibrutinib (I) and immunomodulatory agent lenalidomide (L) have moderate activity as single agents and result in synthetic lethality when combined in non-GCB DLBCL models (Yang, Cancer Cell 2012). When added to chemotherapy for DLBCL as single agents, neither I nor L have significantly improved outcomes over chemotherapy alone as they only result in synthetic lethality with each other. In relapsed non-GCB DLBCL, a phase Ib trial of rituximab (R), L and I resulted in an overall response rate (ORR) of 65% and median duration of response of 15.9 months (Goy, Blood 2019). Both I and L are also immunomodulatory, shifting from a tumor-mediated immune anergy to an anti-tumor immune response.
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- 2019
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47. A LIMITATION OF FLUORESCENCE IN SITU HYBRIDIZATION (FISH) ASSAYS TARGETING SEX CHROMOSOMES FOR MONITORING OF EARLY RELAPSE AFTER TRANSPLANTATION
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Kishi, Yukiko, Kami, Masahiro, Kogi, Mieko, Oki, Yasuhiro, Machida, Utako, Kanda, Yoshinobu, Ueyama, Jun-ichi, Morinaga, Shin-ichi, and Muto, Yoshitomo
- Published
- 2001
48. Older Patients (pts) with Previously Untreated Classical Hodgkin Lymphoma (cHL): A Detailed Analysis from the Phase 3 ECHELON-1 Study
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Evens, Andrew M., Connors, Joseph M., Younes, Anas, Ansell, Stephen M., Kim, Won Seog, Radford, John, Feldman, Tatyana A., Tuscano, Joseph, Savage, Kerry J, Oki, Yasuhiro, Grigg, Andrew P., Pocock, Christopher, Dlugosz-Danecka, Monika, Fenton, Keenan, Engley, Gerald, Liu, Rachael, Miao, Harry, Jolin, Hina, Gautam, Ashish, and Gallamini, Andrea
- Abstract
Evens: Acerta: Consultancy; Pharmacyclics International DMC: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Tesaro: Research Funding; Novartis: Consultancy. Connors:Merck: Research Funding; Amgen: Research Funding; Takeda: Research Funding; Roche Canada: Research Funding; NanoString Technologies: Patents & Royalties: Named Inventor on a patent licensed to NanoString Technologies, Research Funding; Seattle Genetics: Honoraria, Research Funding; Janssen: Research Funding; F Hoffmann-La Roche: Research Funding; Bayer Healthcare: Research Funding; Cephalon: Research Funding; Bristol Myers-Squibb: Research Funding; Lilly: Research Funding; Genentech: Research Funding. Younes:Sanofi: Honoraria; Merck: Honoraria; Astra Zeneca: Research Funding; Celgene: Honoraria; Incyte: Honoraria; Seattle Genetics: Honoraria; Bayer: Honoraria; Novartis: Research Funding; Curis: Research Funding; J&J: Research Funding; Genentech: Research Funding; Takeda: Honoraria; Roche: Honoraria, Research Funding; Abbvie: Honoraria; Janssen: Honoraria, Research Funding; Pharmacyclics: Research Funding; BMS: Honoraria, Research Funding. Ansell:Merck & Co: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Celldex: Research Funding; Bristol-Myers Squibb: Research Funding. Radford:Takeda: Consultancy, Research Funding, Speakers Bureau; GlaxoSmithKline: Equity Ownership; AstraZeneca: Equity Ownership; Seattle Genetics: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Pfizer: Research Funding; Celgene: Research Funding; BMS: Consultancy, Speakers Bureau. Feldman:Seattle Genetics: Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Johnson and Johnson: Speakers Bureau; Celgene: Speakers Bureau; Portola: Research Funding; KITE: Speakers Bureau. Tuscano:Takeda: Research Funding; Genentech: Consultancy, Research Funding; Amgen: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding. Oki:Seattle Genetics: Research Funding; Takeda Millenium: Honoraria, Research Funding; Jazz Pharmaceuticals: Employment. Grigg:Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Pocock:Kent & Canterbury Hospital: Employment. Dlugosz-Danecka:Roche: Consultancy; Servier: Consultancy. Fenton:Seattle Genetics, Inc.: Employment, Equity Ownership. Engley:Seattle Genetics: Employment. Liu:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Miao:Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Jolin:Takeda Pharmaceuticals International Co.: Employment. Gautam:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Gallamini:Takeda: Consultancy, Speakers Bureau.
- Published
- 2018
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49. Older Patients (pts) with Previously Untreated Classical Hodgkin Lymphoma (cHL): A Detailed Analysis from the Phase 3 ECHELON-1 Study
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Evens, Andrew M., Connors, Joseph M., Younes, Anas, Ansell, Stephen M., Kim, Won Seog, Radford, John, Feldman, Tatyana A., Tuscano, Joseph, Savage, Kerry J, Oki, Yasuhiro, Grigg, Andrew P., Pocock, Christopher, Dlugosz-Danecka, Monika, Fenton, Keenan, Engley, Gerald, Liu, Rachael, Miao, Harry, Jolin, Hina, Gautam, Ashish, and Gallamini, Andrea
- Abstract
Background
- Published
- 2018
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50. Pralatrexate in Combination with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Previously Untreated Patients with Peripheral T-Cell Lymphoma (PTCL): A Phase 1 Dose-Escalation Study
- Author
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Shustov, Andrei, Johnston, Patrick B, Barta, Stefan Klaus, Bhat, Gajanan, Reddy, Guru, and Oki, Yasuhiro
- Abstract
Shustov: Celgene: Other: Publication assistance; Spectrum Pharmaceuticals: Consultancy, Research Funding. Bhat: Spectrum Pharmaceuticals: Employment. Reddy: Spectrum Pharmaceuticals: Employment.
- Published
- 2017
- Full Text
- View/download PDF
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