Kategorie: Maligní lymfomy a leukémie
Téma: Chronic lymphocytic leukemia - Clinical studies
Číslo abstraktu: P096
Autoři: MUDr. Lukáš Smolej, Ph.D.; MUDr. Yvona Brychtová, Ph.D.; MUDr. Eduard Cmunt, CSc.; prof. MUDr. Michael Doubek, Ph.D.; MUDr. Martin Špaček, Ph.D.; MUDr. David Belada, Ph.D.; MUDr. Monika Motyčková; MUDr. Irena Zygulová; MUDr. Dagmar Adamová; MUDr. Vít Procházka, Ph.D.; MUDr. Martin Šimkovič; Ing. Kateřina Klásková; doc. MUDr. Tomáš Kozák, Ph.D., MBA
Combination of fludarabine, cyclophosphamide and rituximab (FCR) is currently considered the treatment of choice in physically fit patients (pts) with chronic lymphocytic leukemia (CLL). However, many patients cannot tolerate this aggresive regimen because of advanced age and/or serious comorbid conditions which may lead to unacceptable toxicity. Protocols based on low-dose fludarabine have recently demonstrated promising results in small studies.
Aims: to assess efficacy and safety of low-dose FCR regimen used in elderly/comorbid patients with CLL/SLL; updated results including first data on progression-free survival (PFS) and overall survival (OS) are presented.
Between March 2009 and July 2012, a total of 207 pts with active disease (CLL, n=196, SLL, n=11) were treated by low-dose FCR at 16 centers cooperating within Czech CLL Study Group. Dose reduction of chemotherapy in comparison to full-dose FCR was following: 50% of fludarabine dose (12 mg/m2 i.v. or 20 mg/m2 orally on days 1-3) and 60% of cyclophosphamide dose (150 mg/m2 i.v./p.o. on days 1-3). Rituximab was administered in standard schedule (375 mg/m2 i.v. day 1 in 1st cycle, 500 mg/m2 i.v. day 1 from 2nd cycle). Treatment was repeated every 4 weeks; antimicrobial prophylaxis with sulfamethoxazol/trimethoprim and aciclovir or equivalents was recommended. Data regarding efficacy and safety are currently available in 199 pts; the descriptive characteristics are summarized in Table 1.
Based on intention-to-treat principle, the overall response rate / complete responses (including clinical CR [without bone marrow biopsy] and CRi [with incomplete marrow recovery] were 79/37% in first line and 64/29% in relapsed/refractory setting. Serious (CTCAE grade III/IV) neutropenia was frequent (57 and 49%) but did not translate into high occurrence of serious infections (14 and 18%, Table 1). The most common causes of death were CLL progression and infections. At the median follow-up of 19 months, median progression- free survival for previously untreated and relapsed/refractory patients was 20 and 15 months; median overall survival has not been reached in previously untreated pts (80% at 2 years) and was 31 months in relapsed/refractory pts. CIRS score and age did not significantly influence PFS or OS.
Summary / Conclusion:
Our data show that treatment of elderly/comorbid patients with CLL/SLL using low-dose FCR has promising efficacy in first line as well as relapsed/refractory disease, including reasonable PFS and OS. Toxicity is acceptable and manageable.
Table 1. Basic characteristics, therapeutic efficacy and severe (CTCAE grade III/IV) toxicity
Datum přednesení příspěvku: 14. 6. 2013