The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform

Wyndham H Wilson - One of the best experts on this subject based on the ideXlab platform.

  • da EPOCH Chemotherapy is highly effective in alk positive and alk negative alcl results of a prospective study of ptcl subtypes in adults
    Blood, 2011
    Co-Authors: Kieron Dunleavy, Seth M. Steinberg, Stefania Pittaluga, Margaret Shovlin, Cliona Grant, Elaine S Jaffe, Wyndham H Wilson
    Abstract:

    Abstract 1618 Background: Anaplastic large cell lymphoma (ALCL) is a distinct type of peripheral T-cell lymphoma (PTCL) characterized histologically, by large anaplastic lymphoid cells that are CD30 positive. There is biologic heterogeneity within ALCL: ALK (anaplastic lymphoma kinase) positive cases harbor a translocation usually involving chromosomes 2 and 5 resulting in over-expression of ALK (variant translocations also occur) whereas ALK negative cases do not. ALK positive ALCL is also clinically distinctive, with a younger age of onset and better treatment outcomes. In the recent International PTCL and Natural Killer (NK) T-Cell Lymphoma Study (Savage et al. Blood.2008: 111 (12)), the outcome for patients with ALK positive compared to ALK negative ALCL was significantly better (5-year failure-free survival (FFS) 60% versus 36%: p=0.15). Methods: We prospectively investigated the efficacy of 6 cycles of DA-EPOCH Chemotherapy in newly diagnosed patients with both ALK positive and ALK negative ALCL and compared their outcome to other subtypes of PTCL. Results: Clinical characteristics of 38 enrolled patients are shown below. 22 patients had a diagnosis of ALCL and other diagnoses were PTCL-NOS (10), hepatosplenic gamma delta T-cell lymphoma (4), enteropathy associated T-cell lymphoma (1) and angioimmunoblastic T-cell lymphoma (1). Patients with ALK positive and ALK negative ALCL had similar characteristics. With a median potential follow-up time of 10.5 years, the 5 year progression-free survival (PFS) probability for ALK positive versus negative patients was 80% versus 71% (p=0.82); 5 year overall survival (OS) was 86% in both groups (p=0.95). For patients with other subtypes of PTCL, PFS and OS were 32% and 50% respectively, at 5-years. Conclusions: In contrast to other reports, patients with ALK negative ALCL had a very favorable outcome following DA-EPOCH Chemotherapy that was no different from that of ALK positive cases. This regimen is highly effective in ALCL, independent of ALK expression. Accrual continues. Disclosures: No relevant conflicts of interest to declare.

  • Potent Single Agent Activity and Tumor Selectivity of Bortezomib in Mantle Cell Lymphoma: First Impressions from a Randomized Phase II Study of EPOCH-Rituximab-Bortezomib in Untreated Mantle Cell Lymphoma.
    Blood, 2005
    Co-Authors: Adrian Wiestner, Kieron Dunleavy, Therese White, Edgar G. Rizzatti, Gerald E. Marti, Wyndham H Wilson
    Abstract:

    The proteasome inhibitor bortezomib is FDA approved for use in Multiple Myeloma and has shown promising single agent activity in patients with relapsed Mantle Cell Lymphoma (MCL), of whom 30–50% respond. We initiated a phase II study investigating the combination of bortezomib (B) with rituximab (R) and dose adjusted (DA), infusional EPOCH Chemotherapy (etoposide, prednisone, vincristine, doxorubicin and cyclophosphamide) in patients with untreated MCL. Patients are treated with one cycle of B 1.5 mg/m 2 i.v. on days 1, 4, 8, and 11; followed by 6 cycles of DA-EPOCH-R-B induction therapy. Patients who achieve at least PR are then randomized to receive B maintenance therapy for 18 months versus observation followed by B if progression occurs. We obtain lymph node biopsies before initiating treatment and on day 2, 12–24 hours after the first dose of bortezomib. In order to analyze the molecular effects of B on tumor cells and to identify predictors of response we plan extensive molecular studies including gene expression profiling and proteomic analysis. Here we report on the effect of single agent B in a 64 year old African American male with leukemic MCL. The patient had been well until a few months prior when he underwent unrelated surgery and was found to have mild anemia and lymphocytosis. When he presented to our institution he had a WBC of 25K/μl, absolute lymphocyte count 19K/μl, Hb 11.7g/dl and platelets 164K/μl. Blood smear revealed medium to large lymphocytes with a high n/c ratio and folded, indented nuclei with prominent nucleoli. Flow cytometry was consistent with MCL. Bone marrow examination showed up to 60% cellularity composed predominantly of an interstitial infiltrate of Cyclin D1 positive lymphocytes. Physical exam and CT scan showed minimal lymphadenopathy but a large spleen measuring 19 cm in cranio-caudal dimension. During his work-up, the lymphocyte count increased further and he became progressively anemic. After informed consent, we initiated the first cycle with single agent B. Following doses #2 and #3, the patient reported grade III–IV fatigue and was briefly hospitalized. At the same time his lymphocyte count dropped from a high of 29K/μl to 15K/μl (day 5, 24 hours after dose #2), to 3,700/μl (day 9) to 2,200/μl (day 12). Flow cytometric analysis showed that B predominantly depleted the leukemic cells; the CD19+ cells dropped from a high of 26K/μl to less than 1,000/μl (day 12 and 14) while the number of T-cells remained in the normal range (Figure). The ANC was unaffected by B and the platelet nadir was 112K/μl. The impressive single agent activity and apparent tumor selectivity of bortezomib in MCL as exemplified by this patient’s response are encouraging. Analyses to characterize the molecular effects of B in the lymphoma cells are ongoing and may help identify the molecular basis for the potent anti-tumor effects of B in MCL.

  • phase ii study of EPOCH infusional Chemotherapy in relapsed or refractory hodgkin s lymphoma hl a report on toxicity efficacy and prognostic indicators of outcome
    Journal of Clinical Oncology, 2004
    Co-Authors: Kieron Dunleavy, Seth M. Steinberg, Therese White, Nicole Grant, E S Jaffe, J Butrynski, Wyndham H Wilson
    Abstract:

    6598 Background: In relapsed/refractory HL, an effective and well tolerated salvage regimen has important roles both prior to autologous stem cell transplant (SCT) and as palliative therapy in patients (pts) who are ineligible for or have failed SCT. Methods: Eligible pts had relapsed/refractory HL and adequate organ function unless due to HL. Pts received fixed dose EPOCH Chemotherapy (etoposide 200 mg/m2, vincristine 1.6 mg/m2 (no cap) and doxorubicin 40 mg/m2 CIVI x 96-hrs D1–4; cyclophosphamide 750 mg/m2 IV D5 and prednisone 60 mg/m2 qd D1–6 ) with G-CSF q21 days until disease progression or stabilization over ≥ 2 cycles. Results: Of 54 pts, median (range) age was 31 yrs (19–64), 35 (66%) were male, stage was III in 11(21%) and IV in 30(56%), and 29 (55%) had B symptoms. Histology included nodular sclerosis 34 (64%), mixed cellularity 3 (25%), and lymphocyte depleted 5 (9%) classical HL, and nodular lymphocyte predominant HL 1 (2%). 24 (45%) pts had had ≥ 2 prior regimens, 27 (51%) pts received chemot...

  • Dose-adjusted EPOCH Chemotherapy for untreated large B-cell lymphomas: A pharmacodynamic approach with high efficacy
    Blood, 2002
    Co-Authors: Wyndham H Wilson, Diane Cole, Deborah Pearson, Nicole Drbohlav, Richard F Little, Michael L Grossbard, Seth M. Steinberg, John Janik, Stefania Pittaluga, Martin Gutierrez
    Abstract:

    We hypothesized that incremental improvements in the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) Chemotherapy regimen through optimization of drug selection, schedule, and pharmacokinetics would improve outcome in patients with large B-cell lymphomas. A prospective multi-institutional study of administration of etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone (EPOCH therapy) was done in 50 patients with previously untreated large B-cell lymphomas. The doses of etoposide, doxorubicin, and cyclophosphamide were adjusted 20% each cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L. The median age of the patients was 46 years (range, 20-88 years); 24% were older than 60 years; and 44% were at high-intermediate or high risk according to International Prognostic Index (IPI) criteria. There was a complete response in 92% of patients, and at the median follow-up time of 62 months, the progression-free survival (PFS) and overall survival (OS) rates were 70% and 73%, respectively. Neither IPI risk factors nor the index itself was associated with response, PFS, or OS. Doses were escalated in 58% of cycles, and toxicity levels were tolerable. Significant inverse correlations were observed between dose intensity and age for all adjusted agents, and drug clearance of doxorubicin and free etoposide was also inversely correlated with age (r = -0.54 and P(2) =.08 and r = -0.45 and P(2) =.034, respectively). Free-etoposide clearance increased significantly during successive cycles (P(2) =.015). Lymphomas with proliferation of at least 80% had somewhat lower progression and those expressing bcl-2 had significantly higher progression (P(2) =.04). Expression of bcl-2 may discriminate the recently described activated B-like from germinal-center B-like large-cell lymphomas and provide important pathobiologic and prognostic information. Dose-adjusted EPOCH may produce more cell kill than CHOP-based regimens. Dynamic dose adjustment may overcome inadequate drug concentrations, particularly in younger patients, and compensate for increased drug clearance over time.

  • Expression of the Multidrug Resistance-Associated Protein Gene in Refractory Lymphoma: Quantitation by a Validated Polymerase Chain Reaction Assay
    Blood, 1997
    Co-Authors: Zhirong Zhan, Wyndham H Wilson, Antonio Tito Fojo, Joanna Regis, Victor Sandor, Erick Gamelin, Bruce Dickstein, Susan E. Bates
    Abstract:

    Previous work investigating the role of MDR-1 overexpression in relapsed and refractory lymphoma led us to investigate a possible role for multidrug resistance-associated protein (MRP) as a cause of resistance in patients who did not overexpress MDR-1 . A quantitative polymerase chain reaction (PCR) method for measuring MRP expression was validated. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein levels. MRP levels were found to be independent of sample tumor content by immunophenotyping, suggesting that the presence of normal cells had no significant impact on measurements of MRP expression. We evaluated MRP in 55 biopsy samples from 40 patients with refractory lymphoma enrolled on a trial of infusional Chemotherapy (EPOCH). Pre- and post-EPOCH samples were available from 15 patients. MRP levels were also evaluated in 16 newly diagnosed, untreated lymphoma patient samples. No significant difference in MRP mRNA expression was noted between pre- and post-EPOCH groups. Also, MRP levels in the newly diagnosed patient samples were not significantly different from either pre- or post-EPOCH groups. Two of 15 paired pre- and post-EPOCH patient samples exhibited overexpression of MRP after EPOCH Chemotherapy, with measured increases of 10-fold and 18-fold. We conclude that MRP overexpression is not responsible for non–P-glycoprotein (Pgp)–mediated drug resistance in the majority of these patients, although it may be important in a subset of patients. Defining this subset prospectively could aid in the development of clinical trials of MRP modulation in drug-resistant lymphoma.

Joseph A. Sparano - One of the best experts on this subject based on the ideXlab platform.

  • response adapted therapy with infusional EPOCH Chemotherapy plus rituximab in hiv associated b cell non hodgkin s lymphoma
    Haematologica, 2020
    Co-Authors: Joseph A. Sparano, Lee Ratner, Juan Carlos Ramos, Richard F Ambinder, Lawrence D. Kaplan, William Wachsman, David M Aboulafia, David H Henry, Ethel Cesarman, Amy Chadburn
    Abstract:

    Four cycles of rituximab plus CHOP Chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4–6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin9s lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036

  • Response-Adapted Therapy with Infusional EPOCH Chemotherapy Plus Rituximab in HIV-Associated, B-Cell Non-Hodgkin's Lymphoma
    Blood, 2019
    Co-Authors: Juan Carlos Ramos, Lee Ratner, Richard F Ambinder, Lawrence D. Kaplan, Joseph A. Sparano, William Wachsman, David M Aboulafia, David H Henry
    Abstract:

    Introduction: Six cycles of rituximab plus infusional EPOCH is considered a preferred regimen for first-line treatment of HIV-associated diffuse large B-cell lymphoma (DLBCL), HHV8-positive DLBCL, and primary effusion lymphoma, and is among the preferred regimens for HIV-associated Burkitt's lymphoma in the 2019 NCCN guidelines. A phase III trial demonstrated non-inferiority of 4 cycles of R-CHOP (followed by 2 additional doses of rituximab) compared with 6 cycles of R-CHOP in immunocompetent patients with low-risk DLBCL (stage I-II, age 18-60 years, and an age-adjusted International Prognostic Index score of 0), indicating that de-escalation of treatment duration may be safely achieved without compromising curability in an appropriately selected patient population. Here we report the outcomes for patients with HIV-associated DLBCL and high-grade non-Hodgkin lymphoma (NHL) treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy under a completed prospective clinical trial (AMC-034). Methods: One hundred-six patients with HIV-associated DLBCL or high-grade CD20-positive NHL enrolled at multiple centers across the U.S. were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of dose-adjusted EPOCH regimen tailored for HIV+ patients. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. Results: Sixty-four of 106 patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms; characteristics of entire population and CR proportions stratified by number of EPOCH treatment cycles were similar (Table 1).The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) due to failure to achieve a CR after 2 cycles (Table 2 and Figure 1). Time to disease progression and overall survival wer also similar for those treated with 4 or fewer cycles compared with 5-6 cycles (91% vs. 87%, and 78% vs. 90%, respectively) (Table 2 and Figure 1). Conclusion: A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in an appropriately selected population of patients with HIV-associated NHL, which merits further evaluation in additional prospective trials. Disclosures Noy: Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding.

  • Predictive Value of Cytokines and Immune Activation Biomarkers in AIDS-Related Non-Hodgkin Lymphoma Treated with Rituximab plus Infusional EPOCH (AMC-034 trial)
    Clinical Cancer Research, 2015
    Co-Authors: Marta Epeldegui, Richard F Ambinder, Joseph A. Sparano, Anna C. Martínez, Daniel P. Widney, Larry Magpantay, Deborah L. Regidor, Ronald T. Mitsuyasu, Otoniel Martínez-maza
    Abstract:

    Purpose: The aims of this study were to determine if pre-treatment plasma levels of cytokines and immune activation-associated molecules changed following treatment for AIDS-NHL with rituximab plus infusional EPOCH, and to determine if pre-treatment levels of these molecules were associated with response to treatment and/or survival. Experimental Design: We quantified plasma levels of B cell activation-associated molecules (sCD27, sCD30, sCD23) and cytokines (IL-6, IL-10, CXCL13) prior to and after the initiation of treatment in persons with AIDS-NHL (n=69) in the AIDS Malignancies Consortium (AMC) 034 study, which evaluated treatment of AIDS-NHL with EPOCH Chemotherapy and rituximab. Results: Treatment resulted in decreased plasma levels of some of these molecules (CXCL13, sCD27, sCD30), with decreased levels persisting for one year following the completion of treatment. Lower levels of CXCL13 before treatment were associated with complete responses following lymphoma therapy. Elevated levels of IL-6 pre-treatment were associated with decreased overall survival, while higher IL-10 levels were associated with shorter progression-free survival, in multivariate analyses. Furthermore, patients with CXCL13 or IL-6 levels higher than the median levels for the NHL group, as well as those who had detectable IL-10, had lower overall survival and PFS, in Kaplan Meier analyses. Conclusions: These results indicate that CXCL13, IL-6 and IL-10 have significant potential as prognostic biomarkers for AIDS-NHL.

  • pooled analysis of aids malignancy consortium trials evaluating rituximab plus chop or infusional EPOCH Chemotherapy in hiv associated non hodgkin lymphoma
    Cancer, 2012
    Co-Authors: Stefan K Barta, Lawrence D. Kaplan, Joseph A. Sparano
    Abstract:

    BACKGROUND: Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) Chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity. METHODS: The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R-EPOCH (n = 51; AMC034). Age-adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/μL vs ≥100/μL), and treatment (R-CHOP vs R-EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event-free survival (EFS) and overall survival (OS). RESULTS: Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ≥100/μL. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R-EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P < .001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P < .01). Treatment-associated death occurred significantly more often in patients with CD4 counts <50/μL (37% vs 6%; P < .01). CONCLUSIONS: The current analysis provided additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIV-associated lymphoma and a CD4 count >50/μL, and the results support the design of an ongoing phase 3 trial comparing concurrent R-EPOCH with R-CHOP in immunocompetent patients with diffuse large B-cell lymphoma (National Clinical Trial no. NCT00118209). Cancer 2012. © 2011 American Cancer Society.

  • Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH Chemotherapy in HIV-associated non-Hodgkin lymphoma.
    Cancer, 2011
    Co-Authors: Stefan K Barta, Lawrence D. Kaplan, Joseph A. Sparano
    Abstract:

    BACKGROUND: Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) Chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity. METHODS: The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R-EPOCH (n = 51; AMC034). Age-adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (

Seth M. Steinberg - One of the best experts on this subject based on the ideXlab platform.

  • da EPOCH Chemotherapy is highly effective in alk positive and alk negative alcl results of a prospective study of ptcl subtypes in adults
    Blood, 2011
    Co-Authors: Kieron Dunleavy, Seth M. Steinberg, Stefania Pittaluga, Margaret Shovlin, Cliona Grant, Elaine S Jaffe, Wyndham H Wilson
    Abstract:

    Abstract 1618 Background: Anaplastic large cell lymphoma (ALCL) is a distinct type of peripheral T-cell lymphoma (PTCL) characterized histologically, by large anaplastic lymphoid cells that are CD30 positive. There is biologic heterogeneity within ALCL: ALK (anaplastic lymphoma kinase) positive cases harbor a translocation usually involving chromosomes 2 and 5 resulting in over-expression of ALK (variant translocations also occur) whereas ALK negative cases do not. ALK positive ALCL is also clinically distinctive, with a younger age of onset and better treatment outcomes. In the recent International PTCL and Natural Killer (NK) T-Cell Lymphoma Study (Savage et al. Blood.2008: 111 (12)), the outcome for patients with ALK positive compared to ALK negative ALCL was significantly better (5-year failure-free survival (FFS) 60% versus 36%: p=0.15). Methods: We prospectively investigated the efficacy of 6 cycles of DA-EPOCH Chemotherapy in newly diagnosed patients with both ALK positive and ALK negative ALCL and compared their outcome to other subtypes of PTCL. Results: Clinical characteristics of 38 enrolled patients are shown below. 22 patients had a diagnosis of ALCL and other diagnoses were PTCL-NOS (10), hepatosplenic gamma delta T-cell lymphoma (4), enteropathy associated T-cell lymphoma (1) and angioimmunoblastic T-cell lymphoma (1). Patients with ALK positive and ALK negative ALCL had similar characteristics. With a median potential follow-up time of 10.5 years, the 5 year progression-free survival (PFS) probability for ALK positive versus negative patients was 80% versus 71% (p=0.82); 5 year overall survival (OS) was 86% in both groups (p=0.95). For patients with other subtypes of PTCL, PFS and OS were 32% and 50% respectively, at 5-years. Conclusions: In contrast to other reports, patients with ALK negative ALCL had a very favorable outcome following DA-EPOCH Chemotherapy that was no different from that of ALK positive cases. This regimen is highly effective in ALCL, independent of ALK expression. Accrual continues. Disclosures: No relevant conflicts of interest to declare.

  • Good outcome of AIDS-related Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with abbreviated cycles of EPOCH-rituximab
    Infectious Agents and Cancer, 2009
    Co-Authors: Kieron Dunleavy, Richard F Little, Seth M. Steinberg, Stefania Pittaluga, Elaine S Jaffe, Nicole Grant, Alan S. Wayne, Robert Yarchoan, Jorge A. Carrasquillo, John Janik
    Abstract:

    The addition of rituximab to CHOP Chemotherapy may augment tumor response but in patients with low CD4 counts, one study suggested that this benefit may be offset by increased infectious deaths (Kaplan. Blood 2005; 106:1538). We hypothesized that the addition of rituximab to EPOCH Chemotherapy could improve tumor kill, allowing fewer cycles of treatment and therefore reducing toxicity. Patients received EPOCH-R (in mg/m2/d – etoposide 50, vincristine 0.4 and doxorubicin 10 all CIV d 1–5; cyclophosphamide 750 mg IV d 5; prednisone 60 po days 1–5 and rituximab 375 IV d 1,5 and G-CSF sc d 6–15) every 21 days. Prophlactic IT methotrexate was administered and HAART was suspended during therapy. Cyclophosphamide was adjusted based on absolute neutrophil count (ANC) nadir. Response was assessed by CT and FDG-PET scan and patients received one cycle beyond CR for a minimum of three cycles. Characteristics of 40 enrolled patients are: median (range) age 42 (9–60) years; IPI 3 (0–4); ECOG PS 1 (1–4), CD4 count 222 (0–835) cells/mm3; HIV viral load 34,766 (0–6,080000) RNA copies/mL; male sex 35 (88%); LDH > N 27 (68%); stage IV 27 (68%) and histology DLBCL 32 (80%) and BL 8 (20%). Of 38 evaluable patients (2NE), median (range) number of cycles given is three (3–5) with CR/CRu in 35 (92%) and PR in one (3%) patients. All eight patients with Burkitt lymphoma are in continuous remission. At four years median potential follow-up, PFS and OS are 86 percent and 70 percent. For patients with CD4 > and 100/mm3 have an extremely favorable outcome with and survival following EPOCH-R. The addition of rituximab did not appear to contribute to infection related complications or deaths. EPOCH-R showed excellent efficacy in eight patients with BL with an OS and PFS of 100 percent. PET scanning has a high negative but low positive predictive value for subsequent relapse. Accrual continues.

  • Long-Term Outcome of AIDS-Related Lymphoma Treated with Abbreviated Cycles of EPOCH-RR: A Prospective Study of 40 Patients
    Blood, 2008
    Co-Authors: Kieron Dunleavy, Richard F Little, Seth M. Steinberg, Stefania Pittaluga, Elaine S Jaffe, Nicole Grant, Alan S. Wayne, Robert Yarchoan, Jorge A. Carrasquillo, John Janik
    Abstract:

    We hypothesized that the addition of rituximab to EPOCH Chemotherapy could improve tumor kill, allowing delivery of fewer cycles of treatment and therefore reducing toxicity. Patients received EPOCH-RR (in mg/m 2 /d – etoposide 50, vincristine 0.4 and doxorubicin 10 all CIV d 1–5; cyclophosphamide 750 mg IV d 5; prednisone 60 po days 1–5 and rituximab 375 IV d 1,5 and G-CSF sc d 6–15) every 21 days. Prophylactic IT methotrexate was administered and HAART was suspended during therapy. Cyclophosphamide was adjusted based on absolute neutrophil count (ANC) nadir. Response was assessed by CT and FDG-PET scan and patients received 1 cycle beyond CR for a minimum of 3 cycles. Characteristics of 40 enrolled patients are: median (range) age 42 (9–60) years; IPI 3 (0–4); ECOG PS 1 (1–4), CD4 count 222 (0–835) cells/mm 3 ; HIV viral load 34,766 (0–6,080000) RNA copies/mL; male sex 35 (88%); LDH > N 27 (68%); stage IV 27 (68%) and histology diffuse large B-cell lymphoma (DLBCL) 32 (80%) and Burkitt lymphoma (BL) 8 (20%). Of 38 evaluable patients (2NE), median (range) number of cycles given is 3 (3–5) with CR/CRu in 35 (92%) and PR in 1 (3%) patients. At 4 years median follow-up, PFS and OS are 86% and 70%, respectively. Eight patients with BL are in continuous CR. For patients with CD4 > and 3 , PFS is 96% and 69%, respectively. IPI did not impact OS and PFS. Early PET scanning (after cycle 2) had a high negative predictive value (100%) but low positive predictive value (20%). Fever/neutropenia occurred on 30%, ANC 3 on 40%, and platelets 3 on 23% of cycles. EPOCH-RR was associated with less CD4 loss - median 128 cells/mm 3 (range +154 to −639) compared to historical data with EPOCH alone (median 189 cells/mm 3 (range +19 to −973). Patients with CD4 3 had good tumor control, but OS was only 31% due to late deaths from advanced AIDS. Patients with CD4 counts > 100/mm 3 had an extremely good PFS and OS. The addition of rituximab did not appear to cause serious infection related complications or deaths. However, one treatment-related death occurred from complications of mycobacterium avium intercellulare. Abbreviated EPOCH-RR is highly effective and tolerable in ARL and enables the administration of fewer treatment cycles (median 3 versus 6). PET scanning has a very high negative but low positive predictive value for subsequent relapse, possibly due to HIV associated PET changes. Accrual continues.

  • phase ii study of EPOCH infusional Chemotherapy in relapsed or refractory hodgkin s lymphoma hl a report on toxicity efficacy and prognostic indicators of outcome
    Journal of Clinical Oncology, 2004
    Co-Authors: Kieron Dunleavy, Seth M. Steinberg, Therese White, Nicole Grant, E S Jaffe, J Butrynski, Wyndham H Wilson
    Abstract:

    6598 Background: In relapsed/refractory HL, an effective and well tolerated salvage regimen has important roles both prior to autologous stem cell transplant (SCT) and as palliative therapy in patients (pts) who are ineligible for or have failed SCT. Methods: Eligible pts had relapsed/refractory HL and adequate organ function unless due to HL. Pts received fixed dose EPOCH Chemotherapy (etoposide 200 mg/m2, vincristine 1.6 mg/m2 (no cap) and doxorubicin 40 mg/m2 CIVI x 96-hrs D1–4; cyclophosphamide 750 mg/m2 IV D5 and prednisone 60 mg/m2 qd D1–6 ) with G-CSF q21 days until disease progression or stabilization over ≥ 2 cycles. Results: Of 54 pts, median (range) age was 31 yrs (19–64), 35 (66%) were male, stage was III in 11(21%) and IV in 30(56%), and 29 (55%) had B symptoms. Histology included nodular sclerosis 34 (64%), mixed cellularity 3 (25%), and lymphocyte depleted 5 (9%) classical HL, and nodular lymphocyte predominant HL 1 (2%). 24 (45%) pts had had ≥ 2 prior regimens, 27 (51%) pts received chemot...

  • Dose-adjusted EPOCH Chemotherapy for untreated large B-cell lymphomas: A pharmacodynamic approach with high efficacy
    Blood, 2002
    Co-Authors: Wyndham H Wilson, Diane Cole, Deborah Pearson, Nicole Drbohlav, Richard F Little, Michael L Grossbard, Seth M. Steinberg, John Janik, Stefania Pittaluga, Martin Gutierrez
    Abstract:

    We hypothesized that incremental improvements in the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) Chemotherapy regimen through optimization of drug selection, schedule, and pharmacokinetics would improve outcome in patients with large B-cell lymphomas. A prospective multi-institutional study of administration of etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone (EPOCH therapy) was done in 50 patients with previously untreated large B-cell lymphomas. The doses of etoposide, doxorubicin, and cyclophosphamide were adjusted 20% each cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L. The median age of the patients was 46 years (range, 20-88 years); 24% were older than 60 years; and 44% were at high-intermediate or high risk according to International Prognostic Index (IPI) criteria. There was a complete response in 92% of patients, and at the median follow-up time of 62 months, the progression-free survival (PFS) and overall survival (OS) rates were 70% and 73%, respectively. Neither IPI risk factors nor the index itself was associated with response, PFS, or OS. Doses were escalated in 58% of cycles, and toxicity levels were tolerable. Significant inverse correlations were observed between dose intensity and age for all adjusted agents, and drug clearance of doxorubicin and free etoposide was also inversely correlated with age (r = -0.54 and P(2) =.08 and r = -0.45 and P(2) =.034, respectively). Free-etoposide clearance increased significantly during successive cycles (P(2) =.015). Lymphomas with proliferation of at least 80% had somewhat lower progression and those expressing bcl-2 had significantly higher progression (P(2) =.04). Expression of bcl-2 may discriminate the recently described activated B-like from germinal-center B-like large-cell lymphomas and provide important pathobiologic and prognostic information. Dose-adjusted EPOCH may produce more cell kill than CHOP-based regimens. Dynamic dose adjustment may overcome inadequate drug concentrations, particularly in younger patients, and compensate for increased drug clearance over time.

Juan Carlos Ramos - One of the best experts on this subject based on the ideXlab platform.

  • response adapted therapy with infusional EPOCH Chemotherapy plus rituximab in hiv associated b cell non hodgkin s lymphoma
    Haematologica, 2020
    Co-Authors: Joseph A. Sparano, Lee Ratner, Juan Carlos Ramos, Richard F Ambinder, Lawrence D. Kaplan, William Wachsman, David M Aboulafia, David H Henry, Ethel Cesarman, Amy Chadburn
    Abstract:

    Four cycles of rituximab plus CHOP Chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4–6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin9s lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036

  • Response-Adapted Therapy with Infusional EPOCH Chemotherapy Plus Rituximab in HIV-Associated, B-Cell Non-Hodgkin's Lymphoma
    Blood, 2019
    Co-Authors: Juan Carlos Ramos, Lee Ratner, Richard F Ambinder, Lawrence D. Kaplan, Joseph A. Sparano, William Wachsman, David M Aboulafia, David H Henry
    Abstract:

    Introduction: Six cycles of rituximab plus infusional EPOCH is considered a preferred regimen for first-line treatment of HIV-associated diffuse large B-cell lymphoma (DLBCL), HHV8-positive DLBCL, and primary effusion lymphoma, and is among the preferred regimens for HIV-associated Burkitt's lymphoma in the 2019 NCCN guidelines. A phase III trial demonstrated non-inferiority of 4 cycles of R-CHOP (followed by 2 additional doses of rituximab) compared with 6 cycles of R-CHOP in immunocompetent patients with low-risk DLBCL (stage I-II, age 18-60 years, and an age-adjusted International Prognostic Index score of 0), indicating that de-escalation of treatment duration may be safely achieved without compromising curability in an appropriately selected patient population. Here we report the outcomes for patients with HIV-associated DLBCL and high-grade non-Hodgkin lymphoma (NHL) treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy under a completed prospective clinical trial (AMC-034). Methods: One hundred-six patients with HIV-associated DLBCL or high-grade CD20-positive NHL enrolled at multiple centers across the U.S. were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of dose-adjusted EPOCH regimen tailored for HIV+ patients. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. Results: Sixty-four of 106 patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms; characteristics of entire population and CR proportions stratified by number of EPOCH treatment cycles were similar (Table 1).The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) due to failure to achieve a CR after 2 cycles (Table 2 and Figure 1). Time to disease progression and overall survival wer also similar for those treated with 4 or fewer cycles compared with 5-6 cycles (91% vs. 87%, and 78% vs. 90%, respectively) (Table 2 and Figure 1). Conclusion: A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in an appropriately selected population of patients with HIV-associated NHL, which merits further evaluation in additional prospective trials. Disclosures Noy: Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding.

  • dose adjusted EPOCH Chemotherapy with bortezomib and raltegravir for human t cell leukemia virus associated adult t cell leukemia lymphoma
    Blood Cancer Journal, 2016
    Co-Authors: Lee Ratner, Daniel Rauch, H Abel, Breanna Caruso, Stefan K Barta, Samir Parekh, Juan Carlos Ramos, Richard F Ambinder, Adrienne A Phillips, John C S Harding
    Abstract:

    Dose-adjusted EPOCH Chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated adult T-cell leukemia lymphoma

  • phase i ii trial of dose adjusted EPOCH Chemotherapy with bortezomib combined with integrase inhibitor therapy for htlv 1 associated t cell leukemia lymphoma
    Retrovirology, 2015
    Co-Authors: Lee Ratner, Daniel Rauch, Stefan K Barta, Juan Carlos Ramos, Richard F Ambinder, Adrienne A Phillips, John C S Harding, Samir Parikh, Hicham H Baydoun, Xiaogang Cheng
    Abstract:

    Adult T-cell leukemia lymphoma (ATLL) acute and lymphoma subtypes have a poor prognosis, with median survival of about one year. The malignant cells are characterized by high levels of nuclear factor kappa B (NFkappaB). In order to improve therapy, we assessed the safety, tolerance, and efficacy of a combination of dose-adjusted EPOCH Chemotherapy (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), combined with proteasome inhibitor, bortezomib, to prevent degradation of the inhibitor of NFkappaB (IkappaB). In addition, integrase inhibitor, raltegravir, was added to the regimen to block virus replication occurring during treatment. This multicenter study enrolled 18 of 20 planned subjects over 2.5 yrs in the U.S., although 15 of the subjects were born in the Caribbean. Six subjects had acute ATLL, and the remainder lymphoma subtype, all but one with stage 4 disease. Therapy was well tolerated; subjects received 1-6 cycles of therapy (mean 4.5 cycles). Two subjects achieved complete remission lasting for >12 mos, 10 subjects had a partial remission, and 3 subjects had stable disease as their best response. Baseline calcium level, absolute lymphocyte count, and proviral DNA load were not predictive of response. Correlations with proviral expression, integration site, and integrase gene analyses will be presented. Supported by NIH grants CA94056, CA1730, CA63413, Lymphoma Leukemia Society grant 6067-10, and Lymphoma Research Foundation grant 307181203. Authors’ details Division of Oncology, Washington University, St Louis, MO, USA. University of Miami, Miami, FL, USA. Lymphoma & Hematology Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Divisions of Hematology-Oncology, Montefiore Hospital, New York, NY, USA. Columbia University, New York, NY, USA. Division of Hematologic Malignancies, Johns Hopkins University, Baltimore, MD, USA. NINDS, NIH, Bethesda, MD, USA.

  • Phase I / II trial of dose adjusted EPOCH Chemotherapy with bortezomib combined with integrase inhibitor therapy for HTLV-1 associated T-cell leukemia lymphoma
    Retrovirology, 2015
    Co-Authors: Lee Ratner, Daniel Rauch, Stefan K Barta, Juan Carlos Ramos, Richard F Ambinder, Adrienne A Phillips, John C S Harding, Samir Parikh, Hicham H Baydoun
    Abstract:

    Adult T-cell leukemia lymphoma (ATLL) acute and lymphoma subtypes have a poor prognosis, with median survival of about one year. The malignant cells are characterized by high levels of nuclear factor kappa B (NFkappaB). In order to improve therapy, we assessed the safety, tolerance, and efficacy of a combination of dose-adjusted EPOCH Chemotherapy (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), combined with proteasome inhibitor, bortezomib, to prevent degradation of the inhibitor of NFkappaB (IkappaB). In addition, integrase inhibitor, raltegravir, was added to the regimen to block virus replication occurring during treatment. This multicenter study enrolled 18 of 20 planned subjects over 2.5 yrs in the U.S., although 15 of the subjects were born in the Caribbean. Six subjects had acute ATLL, and the remainder lymphoma subtype, all but one with stage 4 disease. Therapy was well tolerated; subjects received 1-6 cycles of therapy (mean 4.5 cycles). Two subjects achieved complete remission lasting for >12 mos, 10 subjects had a partial remission, and 3 subjects had stable disease as their best response. Baseline calcium level, absolute lymphocyte count, and proviral DNA load were not predictive of response. Correlations with proviral expression, integration site, and integrase gene analyses will be presented. Supported by NIH grants CA94056, CA1730, CA63413, Lymphoma Leukemia Society grant 6067-10, and Lymphoma Research Foundation grant 307181203. Authors’ details Division of Oncology, Washington University, St Louis, MO, USA. University of Miami, Miami, FL, USA. Lymphoma & Hematology Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Divisions of Hematology-Oncology, Montefiore Hospital, New York, NY, USA. Columbia University, New York, NY, USA. Division of Hematologic Malignancies, Johns Hopkins University, Baltimore, MD, USA. NINDS, NIH, Bethesda, MD, USA.

Lawrence D. Kaplan - One of the best experts on this subject based on the ideXlab platform.

  • response adapted therapy with infusional EPOCH Chemotherapy plus rituximab in hiv associated b cell non hodgkin s lymphoma
    Haematologica, 2020
    Co-Authors: Joseph A. Sparano, Lee Ratner, Juan Carlos Ramos, Richard F Ambinder, Lawrence D. Kaplan, William Wachsman, David M Aboulafia, David H Henry, Ethel Cesarman, Amy Chadburn
    Abstract:

    Four cycles of rituximab plus CHOP Chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4–6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin9s lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036

  • Response-Adapted Therapy with Infusional EPOCH Chemotherapy Plus Rituximab in HIV-Associated, B-Cell Non-Hodgkin's Lymphoma
    Blood, 2019
    Co-Authors: Juan Carlos Ramos, Lee Ratner, Richard F Ambinder, Lawrence D. Kaplan, Joseph A. Sparano, William Wachsman, David M Aboulafia, David H Henry
    Abstract:

    Introduction: Six cycles of rituximab plus infusional EPOCH is considered a preferred regimen for first-line treatment of HIV-associated diffuse large B-cell lymphoma (DLBCL), HHV8-positive DLBCL, and primary effusion lymphoma, and is among the preferred regimens for HIV-associated Burkitt's lymphoma in the 2019 NCCN guidelines. A phase III trial demonstrated non-inferiority of 4 cycles of R-CHOP (followed by 2 additional doses of rituximab) compared with 6 cycles of R-CHOP in immunocompetent patients with low-risk DLBCL (stage I-II, age 18-60 years, and an age-adjusted International Prognostic Index score of 0), indicating that de-escalation of treatment duration may be safely achieved without compromising curability in an appropriately selected patient population. Here we report the outcomes for patients with HIV-associated DLBCL and high-grade non-Hodgkin lymphoma (NHL) treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy under a completed prospective clinical trial (AMC-034). Methods: One hundred-six patients with HIV-associated DLBCL or high-grade CD20-positive NHL enrolled at multiple centers across the U.S. were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of dose-adjusted EPOCH regimen tailored for HIV+ patients. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. Results: Sixty-four of 106 patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms; characteristics of entire population and CR proportions stratified by number of EPOCH treatment cycles were similar (Table 1).The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) due to failure to achieve a CR after 2 cycles (Table 2 and Figure 1). Time to disease progression and overall survival wer also similar for those treated with 4 or fewer cycles compared with 5-6 cycles (91% vs. 87%, and 78% vs. 90%, respectively) (Table 2 and Figure 1). Conclusion: A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in an appropriately selected population of patients with HIV-associated NHL, which merits further evaluation in additional prospective trials. Disclosures Noy: Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding.

  • pooled analysis of aids malignancy consortium trials evaluating rituximab plus chop or infusional EPOCH Chemotherapy in hiv associated non hodgkin lymphoma
    Cancer, 2012
    Co-Authors: Stefan K Barta, Lawrence D. Kaplan, Joseph A. Sparano
    Abstract:

    BACKGROUND: Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) Chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity. METHODS: The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R-EPOCH (n = 51; AMC034). Age-adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (<100/μL vs ≥100/μL), and treatment (R-CHOP vs R-EPOCH) were included as variables in a multivariate logistic regression model for complete response (CR) and in a Cox proportional hazards regression models for event-free survival (EFS) and overall survival (OS). RESULTS: Features that were associated significantly with an improved CR rate and improved EFS and OS included a low aaIPI score and a baseline CD4 count ≥100/μL. When the analysis was adjusted for aaIPI and CD4 count, patients who received concurrent R-EPOCH had improved EFS (hazard ratio [HR] 0.40; 95% confidence intervals [CI], 0.23, 0.69; P < .001) and OS (HR, 0.38; 95% CI, 0.21, 0.69; P < .01). Treatment-associated death occurred significantly more often in patients with CD4 counts <50/μL (37% vs 6%; P < .01). CONCLUSIONS: The current analysis provided additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIV-associated lymphoma and a CD4 count >50/μL, and the results support the design of an ongoing phase 3 trial comparing concurrent R-EPOCH with R-CHOP in immunocompetent patients with diffuse large B-cell lymphoma (National Clinical Trial no. NCT00118209). Cancer 2012. © 2011 American Cancer Society.

  • Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH Chemotherapy in HIV-associated non-Hodgkin lymphoma.
    Cancer, 2011
    Co-Authors: Stefan K Barta, Lawrence D. Kaplan, Joseph A. Sparano
    Abstract:

    BACKGROUND: Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) Chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity. METHODS: The authors performed a pooled analysis of 2 consecutive trials that included 150 patients with HIV-associated NHL who received either R-CHOP (n = 99; Acquired Immunodeficiency Syndrome [AIDS] Malignancy Consortium Trial 010 [AMC010]) or R-EPOCH (n = 51; AMC034). Age-adjusted International Prognostic Index (aaIPI), CD4 count at lymphoma diagnosis (

  • pooled analysis of aids malignancy consortium amc trials evaluating rituximab plus either chop or infusional EPOCH Chemotherapy in hiv associated non hodgkin s lymphoma
    Blood, 2010
    Co-Authors: Stefan K Barta, Joseph A. Sparano, Lawrence D. Kaplan
    Abstract:

    Abstract 1797 Background: Two consecutively performed randomized studies by the AMC evaluating chemoimmunotherapy for the treatment of HIV-associated NHL include AMC010 (Kaplan LD et al, Blood 2005: concurrent Rituximab [R] + CHOP vs. CHOP, N=150) and AMC034 (Sparano JA et al, Blood 2010: concurrent R+EPOCH vs. Sequential EPOCH → R; N=106). In AMC010, the addition of Rituximab to CHOP was associated with an increased risk of infectious death (15% vs. 2%, p=0.04) without a significant improvement in complete response (CR) rate (58% vs.47%; p=0.15), event free survival (EFS), or overall survival (OS). In AMC034, the CR rate met its primary efficacy endpoint in the concurrent arm (73%; 95% confidence intervals [CI] 58%, 85%) but not the sequential arm (55%; 95% CI 41%, 68%). Methods: We performed a pooled analysis of these two consecutive trials including patients treated with R-CHOP and concurrent R-EPOCH in order to determine the influence of the age-adjusted International Prognostic Index (aaIPI), CD4 count ( Results: The characteristics and outcomes of the study populations are shown in table 1. Patients treated with R-EPOCH tended to have better outcomes in both the low and high risk IPI groups. In a multivariate analysis that included pooled data from both consecutive studies, features that were significantly associated with improved EFS, OS, and CR rate included low aaIPI score and baseline CD4 count of at least 100/ul. Additionally patients treated with concurrent R-EPOCH exhibited improved EFS and OS even when adjusted for prognostic covariates including aaIPI score and CD4 count (table 2). Conclusions: These findings suggest that treatment outcomes may be superior with concurrent R-EPOCH compared with R-CHOP, and support the design of an ongoing phase III trial comparing concurrent R-EPOCH with R-CHOP in immunocompetent patients with diffuse, large B-cell lymphoma (NCT00118209). This analysis provides additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIV-associated lymphoma. Acknowledgements: This study is presented on behalf of the AIDS Malignancy Consortium. Disclosures: No relevant conflicts of interest to declare.