Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma
Alessandro Rambaldi, Manuela Lazzari, Cristina Manzoni, Emanuela Carlotti, Luca Arcaini, Michele Baccarani, Tiziano Barbui, Carlo Bernasconi, Giuseppe Dastoli, Giovanna Fuga, Enrica Gamba, Livio Gargantini, Valter Gattei, Francesco Lauria, Mario Lazzarino, Franco Mandelli, Enrica Morra, Alessandro Pulsoni, Michela Ribersani, Pier Luigi Rossi-Ferrini, Maurizio Rupolo, Sante Tura, Vittorina Zagonel, Francesco Zaja, PierLuigi Zinzani, Gigliola Reato, Robin Foa, Alessandro Rambaldi, Manuela Lazzari, Cristina Manzoni, Emanuela Carlotti, Luca Arcaini, Michele Baccarani, Tiziano Barbui, Carlo Bernasconi, Giuseppe Dastoli, Giovanna Fuga, Enrica Gamba, Livio Gargantini, Valter Gattei, Francesco Lauria, Mario Lazzarino, Franco Mandelli, Enrica Morra, Alessandro Pulsoni, Michela Ribersani, Pier Luigi Rossi-Ferrini, Maurizio Rupolo, Sante Tura, Vittorina Zagonel, Francesco Zaja, PierLuigi Zinzani, Gigliola Reato, Robin Foa
Abstract
Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m(2) intravenously, weekly for 4 weeks). After CHOP, 57% achieved a complete response (CR), 37% a partial response (PR), and 6% were nonresponders (NR). At this stage, patients proving PCR-negative (n = 41) or failing to achieve a clinical response (n = 8) were excluded from rituximab treatment. Seventy-seven patients received rituximab and entered a scheduled MRD follow-up program. At the first molecular follow-up (+12 weeks), 59% had converted to PCR negativity in the BM and PB, with a further increase documented at the second control (+28 weeks) with 74% PCR negative. At the last molecular follow-up (+44 weeks), 63% of the patients remained PCR negative. At 3 years, the estimated overall survival of all patients is 95% (95% confidence interval [CI], 86-98). For patients achieving PCR-negative status following CHOP and therefore excluded from rituximab treatment, freedom from recurrence (FFR) was 52% (95% CI, 28-71). For patients treated with rituximab, a durable PCR-negative status was associated with a better clinical outcome since FFR was 57% (95% CI, 23-81) compared with 20% (95% CI, 4-46) in patients who never achieved or lost the molecular negativity (P <.001).
Source: PubMed