10 results on '"Abramson JS"'
Search Results
2. Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study.
- Author
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Wang M, Siddiqi T, Gordon LI, Kamdar M, Lunning M, Hirayama AV, Abramson JS, Arnason J, Ghosh N, Mehta A, Andreadis C, Solomon SR, Kostic A, Dehner C, Espinola R, Peng L, Ogasawara K, Chattin A, Eliason L, and Palomba ML
- Subjects
- Adult, Aged, Humans, Immunotherapy, Adoptive adverse effects, Neoplasm Recurrence, Local drug therapy, Antineoplastic Agents adverse effects, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Mantle-Cell, Neutropenia chemically induced
- Abstract
Purpose: To report the primary analysis results from the mantle cell lymphoma (MCL) cohort of the phase I seamless design TRANSCEND NHL 001 (ClinicalTrials.gov identifier: NCT02631044) study., Methods: Patients with relapsed/refractory (R/R) MCL after ≥two lines of previous therapy, including a Bruton tyrosine kinase inhibitor (BTKi), an alkylating agent, and a CD20-targeted agent, received lisocabtagene maraleucel (liso-cel) at a target dose level (DL) of 50 × 10
6 (DL1) or 100 × 106 (DL2) chimeric antigen receptor-positive T cells. Primary end points were adverse events (AEs), dose-limiting toxicities, and objective response rate (ORR) by independent review committee per Lugano criteria., Results: Of 104 leukapheresed patients, liso-cel was infused into 88. Median (range) number of previous lines of therapy was three (1-11) with 30% receiving ≥five previous lines of therapy, 73% of patients were age 65 years and older, 69% had refractory disease, 53% had BTKi refractory disease, 23% had TP53 mutation, and 8% had secondary CNS lymphoma. Median (range) on-study follow-up was 16.1 months (0.4-60.5). In the efficacy set (n = 83; DL1 + DL2), ORR was 83.1% (95% CI, 73.3 to 90.5) and complete response (CR) rate was 72.3% (95% CI, 61.4 to 81.6). Median duration of response was 15.7 months (95% CI, 6.2 to 24.0) and progression-free survival was 15.3 months (95% CI, 6.6 to 24.9). Most common grade ≥3 treatment-emergent AEs were neutropenia (56%), anemia (37.5%), and thrombocytopenia (25%). Cytokine release syndrome (CRS) was reported in 61% of patients (grade 3/4, 1%; grade 5, 0), neurologic events (NEs) in 31% (grade 3/4, 9%; grade 5, 0), grade ≥3 infections in 15%, and prolonged cytopenia in 40%., Conclusion: Liso-cel demonstrated high CR rate and deep, durable responses with low incidence of grade ≥3 CRS, NE, and infections in patients with heavily pretreated R/R MCL, including those with high-risk, aggressive disease.- Published
- 2024
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3. Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity.
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Jacobson CA, Hunter BD, Redd R, Rodig SJ, Chen PH, Wright K, Lipschitz M, Ritz J, Kamihara Y, Armand P, Nikiforow S, Rogalski M, Maakaron J, Jaglowski S, Maus MV, Chen YB, Abramson JS, Kline J, Budde E, Herrera A, Mei M, Cohen JB, Smith SD, Maloney DG, Gopal AK, Frigault MJ, and Acharya UH
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- Adult, Aged, Antigens, CD19 adverse effects, Antigens, CD19 metabolism, B7-H1 Antigen metabolism, Biological Products, Biomarkers blood, C-Reactive Protein metabolism, Clinical Trials as Topic, Cytokine Release Syndrome etiology, Ferritins blood, Humans, Immunotherapy, Adoptive adverse effects, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Middle Aged, Neoplasm Grading, Neurotoxicity Syndromes etiology, Patient Selection, Progression-Free Survival, Receptors, Chimeric Antigen metabolism, Recurrence, Retrospective Studies, Survival Rate, T-Lymphocytes metabolism, Young Adult, Antigens, CD19 therapeutic use, Lymphoma, Large B-Cell, Diffuse therapy
- Abstract
Purpose: Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting., Patients and Methods: One hundred twenty-two patients from 7 medical centers in the United States were treated with axi-cel and were included in a modified intent-to-treat (mITT) analysis. Seventy-six patients (62%) were ineligible for the ZUMA-1 trial. Response and toxicity rates, duration of response (DOR), survival, and covariates are described on the basis of the mITT population. Correlative studies on blood and tumor samples were performed to investigate potential biomarkers of response and resistance., Results: Median follow-up was 10.4 months. In the mITT population, the best overall and complete response (CR) rates were 70% and 50%, respectively. Median DOR and progression-free survival (PFS) were 11.0 and 4.5 months in all patients and were not reached (NR) in CR patients. Median overall survival (OS) was NR; 1-year OS was 67% (95% CI, 59% to 77%). Although response rates were similar in the ZUMA-1-eligible and ZUMA-1-ineligible groups (70% v 68%), there was a statistically significant improvement in CR rate (63% v 42%, P = .016), DOR (median, NR v 5.0 months; P = .014), PFS (median, NR v 3.3 months; P = .020), and OS (1-year OS, 89% v 54%; P < .001) in patients who were ZUMA-1 eligible. Rates of grade ≥ 3 cytokine release syndrome and neurotoxicty were 16% and 35%, respectively., Conclusion: Axi-cel yields similar rates of overall response and toxicity in commercial and trial settings, although CR rates and DOR were more favorable in patients eligible for ZUMA-1.
- Published
- 2020
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4. Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma.
- Author
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Roschewski M, Dunleavy K, Abramson JS, Powell BL, Link BK, Patel P, Bierman PJ, Jagadeesh D, Mitsuyasu RT, Peace D, Watson PR, Hanna WT, Melani C, Lucas AN, Steinberg SM, Pittaluga S, Jaffe ES, Friedberg JW, Kahl BS, Little RF, Bartlett NL, Fanale MA, Noy A, and Wilson WH
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Burkitt Lymphoma pathology, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prednisone administration & dosage, Prognosis, Risk Factors, Rituximab administration & dosage, Survival Rate, Vincristine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy
- Abstract
Purpose: Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma., Methods: We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS)., Results: Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare., Conclusion: Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
- Published
- 2020
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5. ADCs, BiTEs, CARs, and Small Molecules: A New Era of Targeted Therapy in Non-Hodgkin Lymphoma.
- Author
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Abramson JS, Ghosh N, and Smith SM
- Subjects
- Antibodies, Bispecific therapeutic use, Antineoplastic Agents therapeutic use, Humans, Immunoconjugates therapeutic use, Immunotherapy, Receptors, Chimeric Antigen, Lymphoma, Non-Hodgkin therapy, Molecular Targeted Therapy
- Abstract
Novel immunotherapies and small molecular inhibitors are transforming our approach to previously treated and newly diagnosed patients across the spectrum of non-Hodgkin lymphomas (NHLs). Anti-CD19 CAR T cells are now indicated for the treatment of relapsed/refractory aggressive B-cell lymphomas after at least two previous lines of therapy in which durable remissions are achieved in approximately 40% of previously incurable patients. Second-line chemoimmunotherapy remains the standard of care at first relapse, but poor outcomes with conventional treatment in this setting creates an appealing rationale for earlier use of CAR T cells, which is currently under investigation, along with even earlier use in selected high-risk patients in the frontline setting. Other emerging immunotherapies include antibody-drug conjugates (ADCs), such as polatuzumab vedotin for multiple-relapsed diffuse large B-cell lymphoma (DLBCL) in combination with bendamustine-rituximab. Multiple bispecific antibodies that bring malignant B cells in contact with effector T cells appear promising in early clinical trials and will likely emerge as off-the-shelf immunotherapy options. Chemotherapy-free small molecule-based regimens are increasingly available for mantle cell (MCLs) and follicular lymphomas (FLs). Bruton tyrosine kinase inhibitors (BTKi) now represent standard second-line therapy for MCL and are being investigated in combination and as initial therapy. Lenalidomide-rituximab is an active regimen in both FL and MCL and may be used in either relapsed/refractory or previously untreated disease. Three PI3K inhibitors are approved for multiple-relapsed FL and can induce durable remissions in patients with chemotherapy- and rituximab-refractory disease. Additional emerging targeted therapies include BCL2 inhibition in MCL and EZH2 inhibition in FL.
- Published
- 2020
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6. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303.
- Author
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Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, and Leonard JP
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cyclophosphamide pharmacology, Cyclophosphamide therapeutic use, Disease-Free Survival, Doxorubicin pharmacology, Doxorubicin therapeutic use, Etoposide pharmacology, Etoposide therapeutic use, Female, Humans, Lymphoma, Large B-Cell, Diffuse mortality, Male, Middle Aged, Prednisone pharmacology, Prednisone therapeutic use, Progression-Free Survival, Vincristine pharmacology, Vincristine therapeutic use, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Purpose: Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma., Patients and Methods: Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety., Results: Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common ( P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm., Conclusion: In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.
- Published
- 2019
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7. Chimeric Antigen Receptor T-Cell Therapies for Aggressive B-Cell Lymphomas: Current and Future State of the Art.
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Abramson JS, Lunning M, and Palomba ML
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- Antigens, CD19, Antigens, Neoplasm, Combined Modality Therapy, Disease Progression, Humans, Lymphoma, B-Cell diagnosis, Neoplasm Grading, Neoplasm Staging, Receptors, Antigen, T-Cell genetics, Receptors, Chimeric Antigen genetics, Treatment Outcome, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Lymphoma, B-Cell immunology, Lymphoma, B-Cell therapy, Receptors, Antigen, T-Cell metabolism, Receptors, Chimeric Antigen metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism
- Abstract
Aggressive B-cell lymphomas that are primary refractory to, or relapse after, frontline chemoimmunotherapy have a low cure rate with conventional therapies. Although high-dose chemotherapy remains the standard of care at first relapse for sufficiently young and fit patients, fewer than one-quarter of patients with relapsed/refractory disease are cured with this approach. Anti-CD19 chimeric antigen receptor (CAR) T cells have emerged as an effective therapy in patients with multiple relapsed/refractory disease, capable of inducing durable remissions in patients with chemotherapy-refractory disease. Three anti-CD19 CAR T cells for aggressive B-cell lymphoma (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene ciloleucel) are either U.S. Food and Drug Administration approved or in late-stage development. All three CAR T cells produce durable remissions in 33%-40% of treated patients. Differences among these products include the specific CAR constructs, costimulatory domains, manufacturing process, dose, and eligibility criteria for their pivotal trials. Notable toxicities include cytokine release syndrome and neurologic toxicities, which are usually treatable and reversible, as well as cytopenias and hypogammaglobulinemia. Incidences of cytokine release syndrome and neurotoxicity differ across CAR T-cell products, related in part to the type of costimulatory domain. Potential mechanisms of resistance include CAR T-cell exhaustion and immune evasion, CD19 antigen loss, and a lack of persistence. Rational combination strategies with CAR T cells are under evaluation, including immune checkpoint inhibitors, immunomodulators, and tyrosine kinase inhibitors. Novel cell products are also being developed and include CAR T cells that target multiple tumor antigens, cytokine-secreting CAR T cells, and gene-edited CAR T cells, among others.
- Published
- 2019
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8. Impact of HIV Infection on the Clinical Presentation and Survival of Non-Hodgkin Lymphoma: A Prospective Observational Study From Botswana.
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Milligan MG, Bigger E, Abramson JS, Sohani AR, Zola M, Kayembe MKA, Medhin H, Suneja G, Lockman S, Chabner BA, and Dryden-Peterson SL
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- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Botswana epidemiology, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Female, HIV Infections complications, HIV Infections epidemiology, HIV Infections virology, Humans, Lymphoma, AIDS-Related epidemiology, Lymphoma, AIDS-Related virology, Lymphoma, Non-Hodgkin complications, Lymphoma, Non-Hodgkin epidemiology, Lymphoma, Non-Hodgkin virology, Male, Middle Aged, Prednisone therapeutic use, Prospective Studies, Rituximab therapeutic use, Treatment Outcome, United States epidemiology, Vincristine therapeutic use, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, Lymphoma, AIDS-Related drug therapy, Lymphoma, Non-Hodgkin drug therapy
- Abstract
Purpose: Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)-an AIDS-defining cancer-in the country., Patients and Methods: This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed., Results: One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001)., Conclusion: Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival.
- Published
- 2018
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9. Extranodal Marginal Zone Lymphoma Presenting As Miliary Lung Disease.
- Author
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Abramson JS, Ferry JA, Muse VV, and Lanuti M
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- Aged, 80 and over, Diagnosis, Differential, Female, Humans, Lymphoma, Mantle-Cell diagnosis, Tuberculosis, Miliary diagnosis
- Published
- 2016
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10. Treatment of favorable, limited-stage Hodgkin's lymphoma with chemotherapy without consolidation by radiation therapy.
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Canellos GP, Abramson JS, Fisher DC, and LaCasce AS
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- Adolescent, Adult, Bleomycin administration & dosage, Combined Modality Therapy, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Female, Hodgkin Disease pathology, Hodgkin Disease therapy, Humans, Male, Retrospective Studies, Salvage Therapy, Treatment Outcome, Vinblastine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Hodgkin Disease drug therapy
- Abstract
Purpose: Limited-stage Hodgkin's lymphoma (HL) has been treated with radiation alone or radiation combined with chemotherapy. Although results in progression-free survival and overall survival have been excellent, the long-term, radiation-induced, toxic cardiac and secondary oncologic complications occurring in succeeding decades have compromised survival of young patients. This study examines the impact of chemotherapy alone in treatment of limited-stage, nonbulky HL, radiation therapy eliminated from primary treatment., Patients and Methods: From 1992 to May 2008, 71 patients with a median age of 29 years (range, 17-44 years) with stages I and II HL without bulky nodes were treated with six cycles of classic combination doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Two patients received six cycles of ABVD-like modification. Two patients received four cycles of ABVD. The ABVD regimen was known to be curative in more advanced disease without radiation therapy., Results: All patients achieved a clinical complete response (CR) or CR unconfirmed. After a median follow-up of at least 60 months (range, at least 12 to at least 204 months), six patients experienced relapse at 6, 10, 11, 16, 20, and 58 months. All relapses occurred at site of presenting disease. No patients have died. Salvage therapy was successful with second-line chemotherapy/radiation and autologous stem-cell transplantation., Conclusion: Six cycles of ABVD is an effective and safe treatment for limited-stage, nonbulky HL and would spare young patients radiation toxicity. Interim positron emission tomography/computed tomography scans in current and future trials may identify those patients who require less than six cycles of chemotherapy.
- Published
- 2010
- Full Text
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