Phase II study on combination therapy with CHOP-Zenapax for HTLV-I associated adult T-cell leukaemia/lymphoma (ATLL) (original) (raw)
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The Lancet Oncology, 2008
Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diff use large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61-80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic eff ects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47•2% after six cycles of CHOP-14 (95% CI 41•2-53•3), 53•0% (47•0-59•1) after eight cycles of CHOP-14, 66•5% (60•9-72•0) after six cycles of R-CHOP-14, and 63•1% (57•4-68•8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5•8% (-2•8-14•4) for eight cycles of CHOP-14, 19•3% (11•1-27•5) for six cycles of R-CHOP-14, and 15•9% (7•6-24•2) for eight cycles of R-CHOP-14. 3-year overall survival was 67•7% (62•0-73•5) for six cycles of CHOP-14, 66•0% (60•1-71•9) for eight cycles of CHOP-14, 78•1% (73•2-83•0) for six cycles of R-CHOP-14, and 72•5% (67•1-77•9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by-1•7% (-10•0-6•6) after eight cycles of CHOP-14, 10•4% (2•8-18•0) after six cycles of R-CHOP-14, and 4•8% (-3•1-12•7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensifi ed regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR [relative risk] 0•76 [0•60-0•95], p=0•0172; six cycles of R-CHOP-14: RR 0•51 [0•40-0•65], p<0•0001; eight cycles of R-CHOP-14: RR 0•54 [0•43-0•69], p<0•0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0•50 [0•38-0•67], p<0•0001), and eight cycles of R-CHOP-14 (RR 0•59 [0•45-0•77], p=0•0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0•63 [0•46-0•85], p=0•0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles. Interpretation Six cycles of R-CHOP-14 signifi cantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justifi ed. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.
Acta Oncologica, 2015
Background. R-CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin ' s lymphoma. It was suggested that decreasing the treatment interval from three weeks (CHOP-21) to two weeks (CHOP-14) may improve survival and disease control of patients with aggressive lymphoma. Purpose. To evaluate the effect of CHOP-like-14 (with or without rituximab) compared to standard CHOP-like -21 on overall survival (OS), disease control and toxicity of patients with aggressive non-Hodgkin lymphoma. Methods. Systematic review and meta-analysis of RCTs. In October 2014 we searched The Cochrane Library, MEDLINE, LILACS, conference proceedings, and databases of ongoing trials. Authors were contacted for complementary data. The primary outcome was OS. Results. We identifi ed seven trials (4073 patients), conducted between the years 1999 and 2008. Trials were at low or unclear risk for selection bias, and at low or unclear risk of attrition bias. CHOP-like-14 improved OS of patients with aggressive lymphoma compared to the same regimen given every 21 days (all trials): HR of death 0.86, 95% confi dence interval (CI) 0.77 -0.97. There was no OS difference between rituximab-CHOP-like 14 to rituximab-CHOP-like-21 (3 trials): HR 0.93 95% CI 0.78 -1.10. The rates of progression or death, complete response, treatment-related mortality, grade 3 -4 infection, and discontinuation were similar between groups. Conclusion. R-CHOP-21 remains the standard of care for patient with aggressive B-cell lymphoma. CHOP-14 can be considered as in case rituximab is omitted.
Blood, 2006
Optimal dose and timing of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for aggressive non-Hodgkin lymphoma (NHL) is still an unresolved issue. We assessed whether dose intensifications with cyclophosphamide and doxorubicin might improve outcome in younger patients with intermediate-risk aggressive NHL. Previously untreated patients were assigned to receive either 8 courses of standard CHOP (n = 239) or 6 courses of intensified (I)–CHOP (n = 238). Although there was a tendency in favor of I-CHOP for overall survival (OS), disease-free survival (DFS), and event-free survival (EFS), the differences were not significant. However, although these analyses were not planned, when the intermediate-risk group was divided into low-intermediate- and high-intermediate-risk patients according to the International Prognostic Index (IPI), low-intermediate-risk patients had improved 6-year OS (67% vs 52%; P = .05), DFS (58% vs 45%; P = .06), and EFS (41% vs 30%; P ...
The Lancet
Background Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. Methods This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7•5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m²), doxorubicin (50 mg/m²), and vincristine (1•4 mg/m², with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m² of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of-5•5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421.
Leukemia, 2009
Lymphoplasmacytic lymphoma (LPL) is an indolent lymphoma with moderate sensitivity to conventional chemotherapy. This study investigated whether the addition of rituximab to standard chemotherapy improves treatment outcome in LPL and the subgroup of LPL patients fulfilling the criteria of Waldenstroem's macroglobulinemia (WM). A total of 69 patients with previously untreated LPL were enrolled into the trial; 64 patients were evaluable for treatment outcome. In all, 48 of the 64 LPL patients fulfilled the criteria of WM. Patients were randomly assigned to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, n ¼ 34) or CHOP (n ¼ 30). R-CHOP resulted in significantly higher overall response (OR) rate (94 vs 67%, P ¼ 0.0085) in the LPL patients and in the WM subgroup (91 vs 60%, P ¼ 0.0188). With a median observation time of 42 months, R-CHOP induced a significantly longer time to treatment failure (TTF) with a median of 63 months for R-CHOP vs 22 months in the CHOP arm in the LPL patients (P ¼ 0.0033) and in the WM subgroup (P ¼ 0.0241). There was no major difference of treatment-associated toxicity between both treatment groups. These data indicate that the addition of rituximab to front-line chemotherapy improves treatment outcome in patients with LPL or WM.
Blood Advances, 2021
Angioimmunoblastic T-cell lymphoma (AITL) is a frequent T-cell lymphoma in the elderly population that has a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Lenalidomide, which has been safely combined with CHOP to treat B-cell lymphoma, has shown efficacy as a single agent in AITL treatment. We performed a multicentric phase 2 trial combining 25 mg lenalidomide daily for 14 days per cycle with 8 cycles of CHOP21 in previously untreated AITL patients aged 60 to 80 years. The primary objective was the complete metabolic response (CMR) rate at the end of treatment. Seventy-eight of the 80 patients enrolled were included in the efficacy and safety analysis. CMR was achieved in 32 (41%; 95% confidence interval [CI], 30%-52.7%) patients, which was below the prespecified CMR rate of 55% defined as success in the study. The 2-year progression-free survival (PFS) was 42.1% (95% CI, 30.9%-52.8%), and the 2-year overall survival was...
Annals of Oncology, 2007
Patients and methods: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. Results: The International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.
British Journal of Haematology
R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non-Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression-free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R-CVP to R-CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R-CVP or R-CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m 2 q 2 months for 12 cycles. Primary endpoint was event-free survival (EFS). Two-hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenstr€ om Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R-CHOP: 127, R-CVP: 123). Median age was 56 years (21-85), 44% were male, 90% were in stage III-IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33Á4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43Á6/50Á9% and 36Á3/60Á8% in the R-CHOP and R-CVP groups (P = 0Á218) respectively. After a median follow-up of 67, 66, and 70 months, five-year EFS was 61% vs. 56% (not significant), progression-free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R-CHOP vs. the R-CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33Á1%) and 18 (15Á3%) patients, P = 0Á001; neutropenia in 16 (11Á6%) and 4 (3Á4%) patients, P = 0Á017; infection in 14 (10Á7%) and 3 (2Á5%) patients,; P = 0Á011; and a second neoplasm in three versus seven patients., in the R-CHOP and the R-CVP groups respectively. This multicentre randomized study with >five-year follow-up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R-CVP or R-CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R-CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second-line therapy.
Journal of Clinical Oncology, 2011
Purpose Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat indolent B-cell lymphoma. Granulocyte colony-stimulating factor (G-CSF), which potentiates antibody-dependent rituximab cytotoxicity, is used to shorten CHOP intervals. To improve progression-free survival (PFS) in patients treated with R-CHOP as the primary end point, we conducted a phase III study. Patients and Methods Patients with untreated stages III to IV indolent B-cell lymphoma were randomly assigned to six cycles of R-CHOP every 3 weeks (R-CHOP-21) or every 2 weeks (R-CHOP-14) with G-CSF. Maintenance rituximab was not allowed. Results Three hundred patients were enrolled. At the median follow-up time of 5.2 years, there was no significant difference in PFS between arms for the 299 eligible patients; the median was 3.7 (R-CHOP-21) v 4.7 (R-CHOP-14) years, 57% v 58% at 3 years, and 41% v 43% at 6 years, respectively (hazard rati...