Prediction of high risk for death in patients with follicular lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in first-line chemotherapy

Abstract

Risk stratification of patients with relapsed and refractory follicular lymphoma (FL) remains challenging. Recently, much attention has been paid to the impact of early progression of disease within 2 years of diagnosis (early POD) on subsequent survival. The aim of this study was to clarify the clinical features and prognostic factors of patients with FL who experienced early POD. Data were available for 94 patients diagnosed with FL (clinical stage II-IV) who had received immunochemotherapy. Early POD was seen in 20 % of these patients. The Cox proportional hazards model showed worse overall survival (OS) in the patients with early POD compared with those without early POD (5-year OS rates 48 % vs. 96 %, P < 0.0001). In multivariate analysis, early POD (P = 0.003) and poor performance status (P = 0.006) remained a significant factor for subsequent OS. In Follicular Lymphoma International Prognostic Index (FLIPI)- and Follicular Lymphoma International Prognostic Index-2 (FLIPI2)-adjusted Cox regression analysis, early POD was associated with markedly reduced OS with a hazard ratio of 11.2 [95 % confidence interval (CI) 3.13-40.3, P < 0.001] and 13.5 (95 % CI 3.22-56.3, P < 0.003), respectively. Among patients who had early POD, high levels of serum lactate dehydrogenase (LDH) both at the time of initial diagnosis and first progression could be associated with worse survival (2-year OS rates 33 vs. 92 %, P < 0.0001). Evaluation of LDH levels at the time of initial diagnosis and first progression may be important to define patients who were associated with worse prognosis. Risk stratification of patients with early POD could lead to improved clinical outcomes for FL patients. Further research is needed to investigate its value for decision making.

Progression‐free survival at 2 years post‐autologous transplant: a surrogate end point for overall survival in follicular lymphoma

“… have identified a subgroup of FL patients treated with chemoimmunotherapy who progressed within the first 2 years after diagnosis and who are at high risk for death after treatment. Another study has recently confirmed this data in a 7.7 years median‐follow cohort of 94 patients with FL who also received first‐line chemoimmunotherapy .…”

“…Murakami et al. also identified high LDH levels as a predictor of early death in patients treated with first‐line chemoimmunotherapy. Furthermore, only ECOG PS>1 and the fact of being rituximab‐naïve at the moment of ASCT had statistical significance in the multivariate analysis.…”

Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure who reach complete response after rescue treatment

“…Follicular lymphoma patients experiencing ETF following first‐line immunochemotherapy lack optimal subsequent treatment and, therefore, ETF has been recently validated as a prognostic marker of poor survival . More recently, complete response at 30 months after ASCT in FL patients has been also described as a surrogate for OS .…”

“…Anti‐CD20 maintenance therapy prolongs remission and probably survival and has become a standard of care after first‐line therapy . Nevertheless, several studies have shown that approximately 15% to 20% of patients with FL will not respond to first‐line immunochemotherapy based on rituximab (refractoriness) or will experience early therapy failure (ETF), defined as relapse or progression within 2 years of commencing first‐line immunochemotherapy . The outcome for this subgroup of high‐risk FL patients is much worse than that of those who respond well to first‐line treatment, with reported 5‐year OS of approximately 50% versus 90% in the latter …”

Comparison Immunochemotherapy and Chemotherapy Efficasy in Follicular Lymphoma

“…Как до «эры ритуксимаба», так и в настоящее время у 10-15 % первичных больных ФЛ протекает нетипично -наблюдается быстрое прогрессирование, отсутствие ответа на противоопухолевое лечение первой линии, а в ряде случаев -рефрактерность, больные в сроки 1,5-2 года после установления диагноза умирают [18]. Еще приблизительно у 20 % больных лимфома рецидивирует в сроки менее чем через 2 года после начала терапии первой линии [19][20][21].…”