The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

Abstract

Treatment of patients with B-cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B-cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m 2 , Day 1), plus bendamustine (70 mg/m 2 , days 1-2), and cytarabine (800 mg/m 2 , Day 1-3; R-BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with very selected high-risk R/R CLL. All patients (median age 60 years, range 53-74) had symptomatic Binet stage B or C active disease requiring treatment, were characterized by adverse cytogenetics (17p deletion, 11q deletion, or both), unmutated immunoglobulin heavy-chain variable region, and were heavily pretreated (1-5, median three previous lines). Overall, R-BAC was well tolerated with limited non-hematological toxicity. Major toxicities were transient Grade 3/4 neutropenia and thrombocytopenia in 84% and 85% of patients, respectively. Overall response rate (OR) was 84%, including complete and partial response in 38% and 46% of patients, respectively. Patients with 17p deletion had an OR of 78%. After a median follow-up of 17 months, median progression-free survival was 16 months while median overall survival (OS) was not reached (1-year OS: 75 6 13%). R-BAC is an active regimen in R/R heavily pretreated high-risk patients with CLL, representing an option for the treatment of patients that are usually refractory to standard therapy. Am. J.

Bendamustine in chronic lymphocytic leukemia: Outcome according to different clinical and biological prognostic factors in the everyday clinical practice

“…The same benefit, on the contrary, has not been observed in the subset of del(17p) patients, were no CRs were registered and the response rate was only 25%. A recent study [18], reported an ORR of 78% for relapsed/refractory CLL patients with del(17p) treated with the combination of rituximab, bendamustine, and cytarabine, suggesting that the addition of cytarabine may overcome the resistance in this particular subset of patients, as also indicated by preclinical data [19].…”

Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia

“…от начала терапии ибрутинибом. Такие результаты можно объяснить коротким сроком на-блюдения [18] за этой когортой больных, поскольку известно, что del(17p) все же сохраняет неблагопри-ятное влияние на показатели выживаемости при терапии ибрутинибом. Так, согласно объединенному анализу результатов 3 исследований (PCYC-1102-1103, RESONATE, RESONATE-17), включавшему 243 пациента с del(17p), при медиане времени наблюдения 28 мес.…”

“…Одним из перспективных направлений в этой области является ингибитор тирозинкиназы Брутона -ибрутиниб, который показал свою эффек-тивность в терапии рецидивов ХЛЛ [16][17][18].…”

Ibrutinib: a paradigm shift in management of CLL

“…[6] The treatment for relapsed CLL is less standardized; repeated therapy with FCR or the use of BR is commonly employed in the relapse setting. [10,11] In the phase II trial of FCR in patients with relapsed CLL the ORR was 74%, with 30% CR. [9] The estimated median OS was 47 months and median PFS was 21 months.…”