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

ABSTRACT: Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.

SUBMITTER: Shadman M

PROVIDER: S-EPMC6553811 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Shadman Mazyar M Li Hongli H Rimsza Lisa L Leonard John P JP Kaminski Mark S MS Braziel Rita M RM Spier Catherine M CM Gopal Ajay K AK Maloney David G DG Cheson Bruce D BD Dakhil Shaker S LeBlanc Michael M Smith Sonali M SM Fisher Richard I RI Friedberg Jonathan W JW Press Oliver W OW

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20180122 7

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untre ...[more]

PMID: 29356608

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Project description:BackgroundDespite an abundance of therapeutic options, advanced-stage follicular lymphoma remains incurable. Furthermore, the ideal sequence and absolute benefit of post-induction therapy is unclear. We designed SWOG S0801 to assess the efficacy and safety of consolidative radioimmunotherapy and sequential maintenance rituximab following chemoimmunotherapy.MethodsFor this single-arm, phase 2, multicentre study, we enrolled patients aged 18 years and older with a diagnosis of stage III, IV, or bulky stage II follicular lymphoma, grades 1, 2, or 3a, who had not received previous therapy, from from 20 institutions within the United States National Cancer Institute Clinical Trials Network. Patients were assigned to a 5-year treatment plan consisting of R-CHOP (rituximab plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2], and prednisone or prednisolone [100 mg]) every 21 days for up to six cycles, with rituximab 375 mg/m2 given on day 1 of cycles 1-4, followed by 131iodine tositumomab radioimmunotherapy and subsequent maintenance rituximab 375 mg/m2 within 12 weeks after the sixth cycle of R-CHOP, every 3 months for up to 4 years. The primary endpoint was 3-year progression-free survival in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial was registered with ClinicalTrials.gov, number NCT00770224.FindingsBetween April 1, 2009, and Dec 15, 2010, we enrolled 84 evaluable patients, of whom 73 completed R-CHOP and radioimmunotherapy. Of 69 patients who registered to maintenance therapy, only 41 completed the 4-year rituximab maintenance treatment. Progression-free survival at 3 years was 90% (95% CI 82-95). The most common grade 3 or worse adverse events included neutropenia in 48 (57%) patients, leucopenia in 34 (40%) patients, thrombocytopenia in 17 (20%) patients, and febrile neutropenia in 14 (17%) patients. Nine patients had possible treatment-related deaths during the study from secondary or unknown causes (n=3), cirrhosis (n=1), cardiac arrest (n=1), and secondary malignancies (n=4). Secondary malignancies occurred in seven patients, including two sarcomas, two colorectal carcinomas, two acute myelogenous leukaemias, and one case of renal-cell carcinoma.InterpretationSWOG S0801 showed near universal responses following chemoimmunotherapy and radioimmunotherapy. However, most discontinuations occurred during maintenance therapy, suggesting that rituximab over a 4-year span is not feasible for many patients. Nonetheless, this sequential therapeutic strategy resulted in good overall outcomes for patients, including a low incidence of early disease progression.FundingThe National Cancer Institute and GlaxoSmithKline.

Project description:BackgroundRituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the current standard therapy for diffuse large B cell lymphoma (DLBCL). Obinutuzumab (G), a glycoengineered, type II anti-CD20 monoclonal antibody, has shown activity and an acceptable safety profile when combined with CHOP (G-CHOP) in patients with advanced DLBCL. We present the final analysis results of the Phase III GOYA study (NCT01287741), which compared the efficacy and safety of G-CHOP versus R-CHOP in patients with previously untreated DLBCL.MethodsPatients aged ≥ 18 years with previously untreated advanced DLBCL were randomly assigned to receive eight 21-day cycles of R or G, plus six or eight cycles of CHOP. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival, other time-to-event endpoints, and safety; investigator-assessed PFS by cell of origin subgroup was an exploratory endpoint.ResultsA total of 1418 patients were randomized, with 1414 included in this final analysis (G-CHOP, N = 704; R-CHOP, N = 710). Five-year PFS rates were 63.8% and 62.6% for G-CHOP and R-CHOP, respectively (stratified hazard ratio 0.94, 95% CI 0.78-1.12; p = 0.48). The results of the secondary efficacy endpoints did not show a benefit of G-CHOP over R-CHOP. In the exploratory analysis, a trend towards benefit with G-CHOP over R-CHOP was apparent in the patients with germinal center B cell DLBCL. The safety profile of G-CHOP was as expected, and no new safety signals were observed. More grade 3-5 (75.1% vs 65.8%), serious (44.4% vs 38.4%), and fatal (6.1% vs 4.4%) adverse events (AEs) were observed in the G-CHOP arm compared with the R-CHOP arm, respectively, with the most common fatal AEs being infections. A higher incidence of late-onset neutropenia occurred in the G-CHOP arm (8.7%) versus the R-CHOP arm (4.9%).ConclusionsThe final analysis, similar to the primary analysis, did not show a PFS benefit of G-CHOP over R-CHOP in previously untreated patients with DLBCL. The results of the secondary endpoints were consistent with the primary endpoint. Further exploratory analyses and investigation of biomarkers are ongoing.

Project description:Background:This multicenter, phase II trial tested the tolerability and efficacy of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma (FL). Patients and methods:Patients with grade 1-3a FL, stage 3-4 or bulky stage 2, FL international prognostic index (FLIPI) 0-2, and no prior therapy were eligible to receive rituximab 375?mg/m2 weekly during cycle 1 and day 1 of cycles 4, 6, 8, and 10, plus lenalidomide 20-25?mg on days 1-21 for twelve 28-day cycles. The primary objectives were to evaluate response rates [complete (CR) and overall] and time to progression. Secondary objectives included toxicity, response according to polymorphisms in FcgR2A and FcgR3A, and changes in circulating pro-angiogenic cells. Results:From October 2010 to September 2011, 66 patients were enrolled. Median age was 53?years, 34 were female, 15 had bulky disease, 21 were FLIPI 0-1, 43 FLIPI 2, and 2 FLIPI 3. One patient withdrew before receiving treatment. Fifty-one patients completed 12 cycles of lenalidomide. Reasons for discontinuation included withdrawal (n?=?6), adverse events (n?=?6), progression (n?=?2). Grade 3-4 hematologic toxicity included neutropenia (21%), lymphopenia (9%), and thrombocytopenia (2%), infection (11%), and rash (8%). Grade 1-2 toxicity included fatigue (78%), diarrhea (37%), rash (32%), and febrile neutropenia in one patient. The overall response rate was 95%; the CR rate was 72% (95% confidence interval, 60% to 83%). With a median follow-up of 5?years, the 2- and 5-year progression-free survival were 86% and 70%, respectively, and the 5-year overall survival was 100%. There was no association between CR rate or PFS and FLIPI, histological grade, bulky disease, FcgR2A/FcgR3A polymorphism, or change in circulating endothelial cell/hematopoietic progenitor cell. Conclusion:Lenalidomide plus rituximab was associated with low rates of grade 3-4 toxicity, yielded a CR rate and PFS similar to chemotherapy-based treatment and may represent a reasonable alternative to immunochemotherapy in previously untreated FL. ClinicalTrials.gov Identifier:NCT01145495.

Dataset Information

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

Publications

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

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