Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia

Robak, Tadeusz; Dmoszyńska, Anna; Solal‐Céligny, Philippe; Warzocha, Krzysztof; Loscertales, Javier; Catalano, John; Afanasiev, Boris; Larratt, Loree; Geisler, Christian H.; Montillo, Marco; Zyuzgin, Ilya; Ganly, Peter; Dartigeas, Caroline; Rosta, András; Maurer, Jörg; Mendila, Myriam; Saville, M. Wayne; Valente, Nancy; Wenger, Michael; Moiseev, I. S.

doi:10.1200/jco.2009.26.4556

Cited by 430 publications

(287 citation statements)

References 44 publications

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“…The OR for all patients was 62%. This rate was comparable with that achieved in pretreated patients within the REACH trial with the FCR regimen and with FC plus alemtuzumab (OR: 69.9% and 67%, respectively) [27,28], and higher than that reported for alemtuzumab monotherapy (OR: 34%) [5]. It is noteworthy that the REACH trial did not include fludarabinerefractory patients, and the 17p deletion was present in only 7% of the patients.…”

Section: Discussionsupporting

confidence: 72%

“…Nevertheless, neutropenic fever was rare (8%). The majority of patients treated with the FCR regimen [27] for relapsed CLL experienced grade III-IV neutropenia (89%), which was complicated by neutropenic fever in 12% of the patients. Because of the presence of adverse events, approximately 50% of refractory patients treated with fludarabine combination regimens need to have dose reductions, skip courses of treatment, or have delays in administration of therapy because of myelosuppression [30,31], while our patients completed the planned 4 R-BAC cycles in 69% of cases with only 9% of cycles that were delayed.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…In this study, Robak et al reported the benefit of chemoimmunotherapy compared to chemotherapy alone in patients with previously treated CLL [9]. The response rates in this trial are consistent with prior phase 2 trials using the identical combination.…”

Section: Commentssupporting

confidence: 76%

The Addition of Rituximab to Fludarabine and Cyclophosphamide Improves Progression-free Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

Mahipal

Weiss

2010

Curr Oncol Rep

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“…22,23 Rituximab was added to the DHAP chemotherapy backbone as it appeared to be of additive value in the relapsed setting when combined with chemotherapy. 24,25 …”

Section: Introductionmentioning

confidence: 99%

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

Gelder

Oers

Alemayehu³

et al. 2016

Bone Marrow Transplant

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Allogeneic stem cell transplantation (alloSCT) remains the only curative option for CLL patients. Whereas active disease at the time of alloSCT predicts poor outcome, no standard remission-induction regimen exists. We prospectively assessed outcome after cisplatin-containing immune-chemotherapy (R-DHAP) followed by alloSCT in 46 patients (median age 58 years) fulfilling modified European Society for Blood and Marrow Transplantation (EBMT) CLL Transplant Consensus criteria being refractory to or relapsed (R/R) o1 year after fludarabine or o 2 years after fludarabine-based immunochemotherapy or R/R with del(17p). Twenty-nine patients received ⩾ 3 cycles of R-DHAP and sixteen o 3 cycles (4 because of disease progression, 8 for toxicity and 4 toxic deaths). Overall rate of response to R-DHAP was 58%, 31 (67%) proceeded to alloSCT after conditioning with fludarabine and 2 Gy TBI. Twenty (65%) remained free from progression at 2 years after alloSCT, including 17 without minimal residual disease. Intention-totreat 2-year PFS and overall survival of the 46 patients were 42 and 51% (35.5 months median follow-up); del(17p) or fludarabine refractoriness had no impact. R-DHAP followed by alloSCT is a reasonable treatment to be considered for high-risk CLL patients without access or resistance to targeted therapies.

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Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia

Abstract: R-FC significantly improved the outcome of patients with previously treated CLL.

Cited by 430 publications

References 44 publications

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

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

The Addition of Rituximab to Fludarabine and Cyclophosphamide Improves Progression-free Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

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