Rituximab Consolidation and Maintenance Immunotherapy Improve Outcome in B-Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2035-2035 ◽  
Author(s):  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
Luca Maurillo ◽  
Francesco Buccisano ◽  
Gianfranco Catalano ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
B Cell ◽  
Response Duration ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Monoclonal antibodies in combination with chemotherapy allowed us to obtain more responses and longer response duration in B-cell chronic lymphocytic leukemia (B-CLL), reducing disease burden to levels detectable only by flow cytometry. Moreover, it has been reported that low-dose rituximab decreases CD20 antigen loss via shaving and promotes enhanced targeting in CLL (Williams, 2006). We performed a phase II study that added rituximab to fludarabine (Flu) as therapy for symptomatic, untreated CLL. Remission status was assessed by a multiparametric flow cytometric method based on the detection of CD19+CD5+CD79b– residual B-CLL lymphocytes. VH mutational status, CD38, ZAP-70 and cytogenetics were obtained in all pts before treatment. We defined as “high risk” pts having at least two of the following markers: unmutated IgVH, CD38>30%, ZAP-70>20%, intermediate/unfavorable cytogenetics (trisomy 12 or del11q or del17p). Eighty-two CLL pts, median age 61 years, received six monthly courses of Flu (25 mg/m2 for 5 days) and four weekly doses of rituximab (375 mg/m2) starting after completion of Flu therapy. According to modified Rai stages, 8 pts had a low stage, 70 an intermediate stage and 4 a high stage. Based on NCI criteria, 66/82 (80%) pts achieved a complete remission (CR), 12/82 (15%) a partial remission (PR) and 4/82 (5%) no response or progression. Hematologic toxicity included mainly neutropenia (grade 3 and/or 4 in 42 pts) and thrombocytopenia (grade 3 and/or 4 in 4 pts). Thirty-five pts in clinical CR or PR, either with CD5+CD19+CD79b– bone marrow (BM) cells >1% (MRD+, n=20 pts) or MRD negative but presenting CD5+CD19+ peripheral blood lymphocytes (PBL) >1000/microl (n=15 pts) within 1 year after completion of the induction treatment, underwent consolidation/maintenance therapy with four monthly cycles of rituximab at 375 mg/m2 followed by twelve monthly doses of rituximab at 150 mg/m2. The median follow-up duration was 46 months. Noteworthy, all B-CLL pts experienced a long progression-free survival (PFS) from the end of induction treatment (68% at 5 years). Nevertheless, CLL pts that underwent consolidation and maintenance therapy (n=35) showed a significant longer response duration (85% at 5 years, Figure). On the other hand, BM and PBL persistently MRD negative (>1 year) pts (n=29) showed a response duration similar to that of the consolidated pts (87% at 5 years). A significant shorter PFS was observed within CD38+ pts (39% vs 78% at 5 years, P=0.002), unmutated pts (45% vs 94% at 2.5 years, P=0.001) and ZAP-70+ pts (36% vs 88% at 6 years; P=0.00002). Notably, within the “high risk” subset (n=30), considering only MRD+ pts in CR or PR (n=20), MRD+ consolidated pts (n=11) showed a significant longer response duration (64% vs 13% at 2 years, P=0.006) in comparison with MRD+ unconsolidated pts (n=9). In conclusion, consolidation/maintenance therapy with rituximab prolongs significantly the response duration in B-CLL, improving also the outcome of the “high risk” subset. Figure Figure

Rituximab Maintenance Following Chemoimmunotherapy Improves Outcome in B-Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2364-2364
Author(s):  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
Dario Ragusa ◽  
Luca Maurillo ◽  
Francesco Buccisano ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
B Cell ◽  
Response Duration ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Abstract 2364 Poster Board II-341 The treatment goal of B-cell chronic lymphocytic leukemia (B-CLL) has already shifted from symptom palliation to the attainment of maximal disease control combining purine analogs with monoclonal antibodies. This immunochemotherapeutic approach resulted both in more complete responses (CR) and longer response duration, often remaining only a minimal residual disease (MRD) detectable by flow cytometry. We treated in first line 120 B-CLL symptomatic patients (pts), median age 62 years, with six monthly courses of intravenous or oral fludarabine at conventional doses and then, after a median time of 31 days, with four weekly doses (375 mg/sqm) of rituximab (rtx). Fourteen pts had a low Rai stage, 103 an intermediate stage and 3 a high stage. We defined as high risk pts having at least two of these markers: unmutated IgVH, CD38>30%, ZAP-70>20%, intermediate unfavorable cytogenetics (trisomy 12 or del11q or del17p). Based on NCI criteria, 92/120 (77%) pts achieved a CR, 24/120 (20%) a partial remission (PR) and 4/120 (3%) no response or progression. Ten pts underwent grade 3 (WHO) infective lung toxicity, 1 patient acute fatal B hepatitis and 2 pts progressed towards Richter's syndrome. Hematologic toxicity included mainly neutropenia (grade 3 and/or 4 in 56 pts) and thrombocytopenia (grade 3 and/or 4 in 8 pts). Fifty-four pts either in CR with B-CLL bone marrow cells >1% (MRD+, n=16 pts) or in CR MRD negative, but with B-CLL peripheral cells going up >1000/microl within 1 year after induction (n=22 pts) or in PR (n=16 pts), underwent consolidation and maintenance therapy with four monthly cycles of rtx at 375 mg/sqm followed by twelve monthly low doses of rtx (150 mg/sqm). The median follow-up duration was 50 months. All treated pts experienced a long progression-free survival from the end of induction treatment (40% at 9 years). On the other hand, global overall survival (OS) was 54% at 10 years. Nevertheless, CLL pts undergoing consolidation and maintenance therapy (n=54) showed a longer response duration vs MRD+ not consolidated pts (n=16; 75% vs 9% at 4 years; P<0.00001, Figure). Noteworthy, persistently MRD negative (>1 year) pts (n=43) showed a very long response duration (79% at 6 years, Figure). Moreover, OS was shorter in MRD+ not consolidated pts (0% vs 79% at 15 years; P=0.0007). Noteworthy, within the high risk subset (n=48), consolidated pts (n=17) showed a longer response duration (56% vs 0% at 2.5 years, P=0.003) vs MRD+ not consolidated pts (n=11). Therefore, rituximab consolidation and maintenance immunotherapy improve response duration in B-CLL, thus potentially increasing OS, also within the high risk subset. Disclosures: No relevant conflicts of interest to declare.

Immunotherapeutic Maintenance Strategy Prolongs Response Duration and Overall Survival Preventing Relapse in Chronic Lymphocytic Leukemia (CLL),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3906-3906 ◽  
Author(s):  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
Pietro Bulian ◽  
Francesco Buccisano ◽  
Annalisa Biagi ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Response Duration ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Prognostic Impact ◽  
Mutational Status ◽  
Grade 3

Abstract Abstract 3906 Today the treatment target of CLL is the attainment of an optimal disease control combining chemotherapy with monoclonal antibodies (MoAbs). This approach produces more complete molecular remissions and longer response duration (RD), remaining often a minimal residual disease (MRD) detectable by flow cytometry. In addition, consolidation and maintenance therapy with MoAbs might provide a further RD and overall survival (OS) benefit in CLL, as it has been already clearly demonstrated in indolent non-Hodgkin lymphomas. We treated in first line 145 CLL symptomatic patients (pts), median age 63 years (37–80), with six monthly courses of intravenous (25 mg/m2) or oral fludarabine (30–40 mg/m2) and then, after a median time of 30 days, with four weekly doses (375 mg/m2) of rituximab (rtx). Before treatment, 15 pts had a modified low Rai stage, 127 an intermediate stage and only 3 a high stage. We defined as high risk pts having at least two of these markers: unmutated IgVH, CD38>30%, ZAP-70>20%, intermediate/poor cytogenetics (trisomy 12 or del11q or del17p). Sixty-three pts (43.5%) belonged to the high risk subset. For MRD flow cytometric study, the threshold was set at >1% CD19+CD5+CD79b+/− bone marrow (BM) CLL cells. Based on NCI criteria (Cheson, 1996), 111/145 (76%) pts achieved a complete remission (CR), 27/145 (19%) a partial remission (PR) and 7/145 (5%) no response or progression. Phenotypic CR (CD19+CD5+CD79b- BM cells <1%) was achieved in 85/145 (59%) CLL pts. Interestingly, MRD+ pts showed a significant shorter overall survival (OS) in comparison with MRD- pts (25% vs 73% at 16 years, P=0.00096). During the induction and consolidation/maintenance time, 13 pts underwent grade 2–3 (sec.WHO) infective lung toxicity and 2 pts progressed towards Richter's syndrome. Hematologic toxicity was mild including mainly neutropenia (grade 3 and/or 4 in 60 pts) and thrombocytopenia (grade 3 and/or 4 in 9 pts). Fifty-nine pts (43%) either in CR with B-CLL BM cells >1% (MRD+, n=16 pts) or in CR MRD negative, but developing MRD positivity within 2 years after induction (n=25 pts) or in PR (n=18 pts), underwent consolidation and maintenance therapy with four monthly cycles of rtx at 375 mg/m2 followed by twelve monthly doses of rtx at 150 mg/m2. The median follow-up duration was 63 months. Noteworthy, both persistently MRD negative pts (n=56) and pts undergoing consolidation/maintenance therapy (n=59) showed a longer RD vs MRD+ not consolidated pts (n=23) [75% vs 58% vs 0% at 5 years; P<0.0001, Figure]. Equally, OS was shorter in MRD+ not consolidated pts in comparison with the other two subsets (0% vs 63% vs 78% at 16 years; P=0.03, Figure). Moreover, ZAP-70+ or unmutated IgVH pts revealed shorter RD (17% vs 53% at 16 years, P=0.001; 16% vs 53% at 6.5 years, P<0.0001). Noteworthy, within the high risk subset (n=63), pts in persistent phenotypic CR (n=18) and consolidated pts (n=23) showed a longer RD (90% vs 66% vs 8% at 2.7 years, P=0.00024) vs MRD+ not consolidated pts (n=15). In multivariate analysis, only consolidation/maintenance (P<0.0001) and biologic risk classes (P=0.001 and P<0.0001) were confirmed as independent prognosticators with regard to RD and OS. Therefore rituximab consolidation/maintenance therapy improve RD and OS in CLL, also within the high risk subset, taking into account that historical biological markers (ZAP-70 and IgVH mutational status) retain their prognostic impact with our chemoimmunotherapeutic strategy. Disclosures: No relevant conflicts of interest to declare.

Frontline Combined Chemoimmunotherapy with Fludarabine, Cyclophosphamide, Alemtuzumab and Rituximab (CFAR) in High-Risk Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 208-208 ◽  
Author(s):  
Sameer A Parikh ◽  
Michael Keating ◽  
Susan O'Brien ◽  
Alessandra Ferrajoli ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Frontline Therapy ◽  
Grade 3 ◽  
Tract Infections ◽  
Cmv Reactivation

Abstract Abstract 208 Background: Combined chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) has excellent clinical activity as frontline therapy for patients (pts) with chronic lymphocytic leukemia (CLL). In a subset of pts who exhibited high-risk features, such as serum beta-2 microglobulin (B2M) ≥4 mg/L; the complete remission (CR) was lower and time to progression (TTP) and overall survival (OS) were shorter; therefore characterizing these pts as high-risk. Alemtuzumab (A) has activity as a single-agent and in combination with F in pts with relapsed/refractory CLL. To improve the CR and OS for pts with high-risk CLL, we added A to the FCR regimen (CFAR) as frontline therapy in a Phase II clinical trial. Methods: All pts who met NCI-WG criteria to initiate therapy, were < 70 years and had a B2M ≥4 mg/L were eligible for the study. Frontline CFAR consisted of C-200 mg/m2 D3-5, F-20mg/m2 D3-5, A-30mg IV D1,3,5, and R-375–500 mg/m2 D2. Courses were repeated every 28 days for a total of 6 courses. All pts received pegylated filgrastim 6mg SC with each course of therapy. All pts received allopurinol for tumor lysis prophylaxis. Antibiotic prophylaxis with TMP/SMX DS and valacyclovir or valganciclovir was also given to all pts. CMV antigenemia was monitored before each course. Results: A total of 60 pts were enrolled from July 2005 through August 2008 (Table). One pt was lost to follow-up. The median age was 59 yrs (range 42–69) and 44 (75%) were male. Median B2M was 5.1 mg/L (4–11.6); HGB was 11.5gm/dL (5.5–15.1); PLT was 139 k/μL(41–446); WBC was 100k/μL (5–665); ALC was 92k/μL (4–619); and 30 pts (51%) were Rai stage III-IV. The median number of courses administered was 4 (2–6); reasons for not completing 6 courses included delayed recovery of counts (18), infection (8), AIHA (4), treatment failure (3) and pt. choice (2). CR was achieved in 70%, nPR in 3%, PR in 18%, and 7% pts did not respond, leading to an ORR of 92% (Table). There was no significant correlation between CR or OR with Rai Stage, IgVH mutation status, FISH status, ZAP70 and CD38 expression. After a median follow-up of 24 months (3–49), 19(32%) pts have progressive disease. Patients with 17p deletion and unmutated IgVH had significantly shorter TTP as shown in the >Table. Eleven (19%) pts have died: 4 with disease progression after achieving CR; 2 who did not respond; 2 with Richter's transformation; 1 transformed into AML; 1 due to metastatic lung cancer; and 1 due to severe pneumonia 8 months after achieving CR. Grade 3/4 neutropenia and thrombocytopenia occurred in 31% and 13% courses. Major infections, including pneumonia and sepsis, were reported for 10(17%) pts. Minor infectious such as bronchitis, urinary tract infections and herpes zoster were reported for 15(25%) pts. In a historic cohort of high-risk pts treated with FCR, grade 3/4 neutropenia and thrombocytopenia occurred in 31% and 10% courses; and major and minor infections were seen in 15% and 23% pts respectively, all comparable to that seen with frontline CFAR. A-associated infusion reactions occurred in 42 (71%) pts. CMV reactivation occurred in 7 (12%) pts, all of whom were on valacyclovir prophylaxis. There was 1 death due to CMV pneumonia; all other episodes of CMV reactivation were promptly treated with valaganciclovir leading to resolution of fever and/or antigenemia. The median OS for all pts has not been reached (49+mo) and the median TTP is 38 months. Conclusion: CFAR is an active frontline regimen in high-risk pts with CLL. Although CR rates in pts with other high-risk features such as 17p deletion and unmutated IgVH were >50%, TTP was significantly shorter for these pts than for pts without these features. With current follow-up, OS, TTP, infectious complications and grade 3/4 hematologic toxicity are comparable to historic high-risk pts treated with FCR. Disclosures: Keating: Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wierda:Genentech: Consultancy, Honoraria; Genzyme: Research Funding.

scholarly journals Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia

2001 ◽  
Vol 12 (7) ◽  
pp. 981-986 ◽  
Author(s):  
U. Novak ◽  
T.J. Grob ◽  
G. Baskaynak ◽  
U.R. Peters ◽  
S. Aebi ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
P73 Gene ◽  
Cell Chronic Lymphocytic Leukemia

FcγRIIIa and FcγRIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1472-1474 ◽  
Author(s):  
Sherif S. Farag ◽  
Ian W. Flinn ◽  
Rama Modali ◽  
Teresa A. Lehman ◽  
Donn Young ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Tumor Clearance ◽  
Grade 3 ◽  
F 33 ◽  
Cell Chronic Lymphocytic Leukemia

Abstract In follicular lymphoma (FL), genomic polymorphisms corresponding to the expression of valine (V) or phenylalanine (F) at amino acid 158 of FcγRIIIa alter the binding affinity of immunoglobulin G1 (IgG1) to the receptor and have been associated with varied responses to rituximab. We examined FcγRIIIa polymorphisms of 30 CLL patients with the phenotypes V/V (n = 6), V/F (n = 12), and F/F (n = 12) treated with thrice-weekly rituximab (375 mg/m2) for 4 weeks to correlate polymorphism type with infusion toxicity and response. Infusion toxicity (grade 3 or greater or hypoxia/hypotension requiring transient cessation of therapy) was observed equally among the groups (V/V, 50%; V/F, 33%; F/F, 41.6%; P = .78). The response to rituximab was also similar among the different polymorphism phenotypes (V/V, 33%; V/F, 41.6%; F/F, 50%). These data suggest that FcγRIIIa polymorphisms are not predictive of response in CLL and that, unlike the case with FL, mechanisms of tumor clearance other than antibody-dependent cellular cytotoxicity may be more important.

Consolidation and Maintenance Immunotherapy with Rituximab Improve Progression Free Survival within ZAP-70 Positive Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2824-2824 ◽  
Author(s):  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
Luca Maurillo ◽  
Francesco Buccisano ◽  
Adriano Venditti ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Mutational Status ◽  
Duration Of Response ◽  
Grade 3

Abstract Clinical studies of monoclonal antibodies combined with chemotherapy have attained more complete responses and longer duration of responses in CLL because this approach reduces disease burden to levels detectable only by immunological or molecular methods. Recent literature data indicate that VH genes, CD38, ZAP-70 protein, and cytogenetic status have a major impact on CLL prognosis. We performed a phase II study that added rituximab sequentially to fludarabine (Flu) as initial therapy for symptomatic, untreated CLL in order to evaluate both the clinical response and outcome. Remission status was also assessed by a multiparametric flow cytometric method based on the detection of CD19+CD5+CD79b− residual B-CLL lymphocytes. VH mutational status, CD38 and cytogenetics were obtained in all pts before treatment. ZAP-70 protein was performed by flow cytometry using an anti-ZAP-70 Alexa Fluor 488 conjugated antibody. Seventy-five CLL pts, median age 60 years, received six monthly courses of Flu (25 mg/m2 for 5 days) and four weekly doses of rituximab (375 mg/m2) starting on an average of thirty days after completion of Flu therapy. According to modified Rai stages, 6 pts had a low stage, 66 an intermediate stage and 3 a high stage. Based on NCI criteria, 61/75 (81%) pts achieved a complete remission (CR), 10/75 (13%) a partial remission (PR) and 4/75 (5%) no response. Three pts presented grade 3 (WHO) infective lung toxicity and 1 patient acute fatal B hepatitis. Hematologic toxicity included neutropenia (grade 3 and/or 4 in 38 pts) and thrombocytopenia (grade 3 and/or 4 in 4 pts). Twenty eight pts, either with CD5+CD19+CD79b− (MRD) bone marrow (BM) cells >1% (n=17 pts) or with CD19+CD5+CD79b− (MRD) peripheral blood lymphocytes (PBL) >1000/microl (n=11 pts) within six months after completion of the induction treatment, underwent consolidation/maintenance therapy with four monthly cycles of rituximab at 375 mg/m2 followed by twelve monthly doses of rituximab at 150 mg/m2. The median follow-up duration was 37 months. Noteworthy, all pts experienced a long progression-free survival (PFS) from treatment (67% at 5 years). Nevertheless, CLL pts that underwent consolidation therapy (n=28) showed a significant longer duration of response (75% vs 27% at 5 years, P=0.002) in comparison with the subset of not consolidated and BM or PBL MRD positive (n=18) CLL pts. Interestingly, BM and PBL MRD negative pts (n=26) showed a duration of response similar to that of the consolidated pts. Moreover, a significant shorter PFS was observed within CD38+ pts (29% vs 79% at 5 years, P=0.005), unmutated pts (0% vs 92% at 2 years, P=0.001), ZAP-70+ pts (29% vs 92% at 5 years; P=0.00003) and within the “poor risk” [trisomy 12 or del 11q or del 17p] cytogenetic subset (0% vs 79% at 2 years, P=0.03). Interestingly, within the ZAP-70+ subset (n=35), the consolidated pts (n=12) showed a longer duration of response (68% vs 0% at 2.6 years, P=0.007) in comparison with the unconsolidated pts (n=11). Therefore, the addition of a consolidation/maintenance therapy with rituximab prolongs significantly the duration of response allowing a better outcome. Moreover, rituximab improves significantly PFS of pts notoriously at worse prognosis, such as ZAP-70+ B-CLL.

Bendamustine Versus Chlorambucil as First-Line Treatment in B Cell Chronic Lymphocytic Leukemia: An Updated Analysis from An International Phase III Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2091-2091 ◽  
Author(s):  
Wolfgang Ulrich Knauf ◽  
Toshko Lissitchkov ◽  
Ali Aldaoud ◽  
Anna Liberati ◽  
Javier Loscertales ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
B Cell ◽  
Dose Intensity ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
First Line ◽  
The Mean ◽  
Grade 3 ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Introduction: Bendamustine is a purine analog/alkylator hybrid agent with a unique mechanism of action, which has shown good clinical efficacy and acceptable tolerability in various hematological malignancies, including Hodgkin’s disease, non-Hodgkin’s lymphoma, and multiple myeloma. Patients and Methods: The efficacy and safety of bendamustine and chlorambucil have been compared in a randomized, open-label, multicenter, Phase III trial in patients with previously untreated advanced (Binet stage B/C) B cell chronic lymphocytic leukemia: an updated analysis from this trial is presented here. Patients were randomized to receive bendamustine (100 mg/m2 on days 1 + 2) or chlorambucil (0.8 mg/kg on days 1 and 15) for up to 6 treatment cycles. The median cumulative dose per patient was 1820 mg and 517 mg for bendamustine and chlorambucil, respectively. The primary endpoints were overall remission rate (ORR), which was defined as complete response, nodular partial response or partial response, and progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. The response to treatment was evaluated by a blinded Independent Response Assessment Committee. Results: A total of 319 patients were randomized (162 bendamustine, 157 chlorambucil), of whom all were included in the efficacy analysis and 312 were evaluable for safety. The mean (± SD) number of treatment cycles was 4.8 ± 1.7 in the bendamustine group and 4.6 ± 1.7 in the chlorambucil group; the median duration of follow-up was 29.2 months (29.8 bendamustine, 27.8 chlorambucil). The ORR was significantly higher with bendamustine than with chlorambucil (67% versus 30%, P&lt;0.0001). The median PFS was 21.5 months with bendamustine and 8.3 months with chlorambucil (P&lt;0.0001). No difference in OS was seen between groups. Most doses were given on schedule. The mean overall relative dose intensity was 86% and 96% in the bendamustine and chlorambucil treatment groups, respectively. At least 1 grade 3/4 neutropenia occurred in 43% of bendamustine-treated patients and 21% of those receiving chlorambucil. Grade 3/4 infections were documented in 7% of bendamustine-treated patients and 4% of chlorambucil-treated patients. Conclusion: This study has shown that bendamustine offers significantly greater efficacy than chlorambucil, with manageable toxicity, and should be considered as first-line chemotherapy for patients with advanced B-CLL.

Phase 3 study of oral lenalidomide as maintenance therapy for patients with B-cell chronic lymphocytic leukemia (CLL).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS7125-TPS7125 ◽  
Author(s):  
Asher Alban Akmal Chanan-Khan ◽  
Andrey Zaritskey ◽  
Miklos Egyed ◽  
Samuel Vokurka ◽  
Olga Samoylova ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Phase 3 ◽  
Cell Chronic Lymphocytic Leukemia
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