Paul A Fields1, William Townsend, Andrew Webb, Nicholas Counsell, Christopher Pocock, Paul Smith, Andrew Jack, Nadjet El-Mehidi, Peter W Johnson, John Radford, David C Linch, David Cunnningham. 1. Paul A. Fields, Guys and St Thomas' and King's College Hospitals; William Townsend, Nicholas Counsell, Paul Smith, and Nadjet El-Mehidi, Cancer Research UK and University College London Cancer Trials Centre; David C. Linch, University College London Hospital; David Cunnningham, Royal Marsden Hospital, London; Andrew Webb, Royal Sussex Cancer Centre, Brighton; Christopher Pocock, Kent and Canterbury Hospital, Kent; Andrew Jack, St James Hospital, Leeds; Peter W. Johnson, Southampton General Hospital, Southampton; and John Radford, Christie Hospital, Manchester, United Kingdom.
Abstract
PURPOSE: The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity. PATIENTS AND METHODS: Sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle. Median age was 76.5 years. All patients had advanced disease; 27 (43.5%) had left ventricular ejection fraction of ≤ 50%, and 35 (56.5%) had an ejection fraction of > 50% and comorbid cardiac risk factors such as ischemic heart disease, diabetes mellitus, or hypertension [Corrected]. Primary end point was overall response rate at the end of treatment. RESULTS: Thirty-eight patients (61.3%; 95% CI, 49.2 to 73.4) achieved disease response (complete response [CR], n = 18; undocumented/unconfirmed CR, n = 6; partial response, n = 14). Two-year progression-free survival for all patients was 49.8% (95% CI, 37.3 to 62.3), and 2-year overall survival was 55.8% (95% CI, 43.3 to 68.4). Thirty-four patients experienced grade ≥ 3 hematologic toxicity. There were 15 cardiac events, of which seven were grade 1 to 2, five were grade 3 to 4, and three were fatal, reflecting the poor cardiac status of the study population. CONCLUSION: Our phase II multicenter trial showed that the R-GCVP regimen is an active, reasonably well-tolerated treatment for patients with DLBCL for whom anthracycline-containing immunochemotherapy was considered unsuitable because of coexisting cardiac disease.
PURPOSE: The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity. PATIENTS AND METHODS: Sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle. Median age was 76.5 years. All patients had advanced disease; 27 (43.5%) had left ventricular ejection fraction of ≤ 50%, and 35 (56.5%) had an ejection fraction of > 50% and comorbid cardiac risk factors such as ischemic heart disease, diabetes mellitus, or hypertension [Corrected]. Primary end point was overall response rate at the end of treatment. RESULTS: Thirty-eight patients (61.3%; 95% CI, 49.2 to 73.4) achieved disease response (complete response [CR], n = 18; undocumented/unconfirmed CR, n = 6; partial response, n = 14). Two-year progression-free survival for all patients was 49.8% (95% CI, 37.3 to 62.3), and 2-year overall survival was 55.8% (95% CI, 43.3 to 68.4). Thirty-four patients experienced grade ≥ 3 hematologic toxicity. There were 15 cardiac events, of which seven were grade 1 to 2, five were grade 3 to 4, and three were fatal, reflecting the poor cardiac status of the study population. CONCLUSION: Our phase II multicenter trial showed that the R-GCVP regimen is an active, reasonably well-tolerated treatment for patients with DLBCL for whom anthracycline-containing immunochemotherapy was considered unsuitable because of coexisting cardiac disease.
Authors: Alden A Moccia; Kimberly Schaff; Ciara Freeman; Paul J Hoskins; Richard J Klasa; Kerry J Savage; Tamara N Shenkier; Randy D Gascoyne; Joseph M Connors; Laurie H Sehn Journal: Blood Adv Date: 2021-03-09