A Phase II Study of Chlorambucil Plus Rituximab Followed by Maintenance Versus Observation In Elderly Patients with Previously Untreated Chronic Lymphocytic Leukemia: Results of the First Interim Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2462-2462 ◽  
Author(s):  
Robin Foa ◽  
Stefania Ciolli ◽  
Francesco Di Raimondo ◽  
Giovanni Del Poeta ◽  
Francesco Lauria ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Interim Analysis ◽  
Overall Response Rate ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
Induction Phase ◽  
First Line ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Binet Stage

Abstract Abstract 2462 Background: Two of the largest trials ever conducted in patients with chronic lymphocytic leukemia (CLL) have shown that the addition of rituximab to fludarabine plus cyclophosphamide (R-FC) significantly improves outcome. However, myelotoxicity and immunosuppression limit the use of this regimen in patients with impaired performance status and pre-existing co-morbidities, predominantly in the elderly. Chlorambucil (CLB) remains a first-line treatment option for such patients. The use of CLB in combination with R is thus an attractive therapeutic option in view of the potentially increased activity compared to CLB alone and the likely good tolerability. This study was designed to determine whether the R-CLB combination is feasible and beneficial as first-line treatment for elderly patients with CLL and to define the role of maintenance R. Patients and Methods: Between October 2008 and January 2010, 97 elderly patients with untreated CD20+ CLL requiring therapy according to the IWCLL criteria were enrolled into the protocol. CLB treatment was administered every 28 days for up to 8 courses at a dose of 8 mg/m2/day p.o. on days 1–7 combined with 375 mg/m2 R for cycle 3 and 500 mg/m2 for cycles 4–8. Responsive patients were randomized to R maintenance (375 mg/m2 every 2 months for 2 years) versus observation. At baseline, blood samples were taken for FISH analysis, IgVH mutational status and expression of Zap-70 and CD38. Minimal residual disease (MRD) was planned to be evaluated on peripheral blood (PB) and bone marrow (BM) cells by four-color flow cytometry and, when required, by PCR. The primary endpoint was the overall response rate at the end of the induction phase defined according to the IWCLL 2008 on the intention-to-treat (ITT) population (all enrolled patients who received at least 1 dose of R). Secondary endpoints included the adverse event (AE) profile, progression-free and overall survival. Results: These are the data of the planned interim analysis based on the first 54 evaluable patients from 19 Italian centers, including tumor response at the end of the induction phase and safety. The median age of patients was 70.5 years (range 61–84): 14.8% were between 61 and 64, 31.5% between 65 and 69, 31.5% between 70 and 74, 16.7% between 75 and 79, and 5.6% were ≥80 years; thus, 53.8% of patients were over the age of 70; 70.4% were males; 25.9% were Binet stage A, 57.4% stage B and 16.7% stage C. The overall incidences of trisomy 12 and abnormalities of 13q, 11q23 and 17p13 were 24.5%, 52.8%, 20.8% and 5.7%, respectively; 7.5% of patients had p53 mutations. Of the 51/54 patients analyzed for the IgVH mutational status, 64.7% were unmutated; of the 53/54 patients studied, 39.6% were CD38+ and 71.7% were Zap-70+. The overall response rate on an ITT analysis was 81.4% (44/54 patients); a CR assessed by CT scan and trephine immunohistochemistry was found in 16.7% of cases (9 patients: 4 in Binet stage A, 3 in stage B and 2 in stage C), a CRi in 3.7% (2 patients), a nPR in 1.9% (1 patient) and a PR in 59.3% (32 patients). Eight of the 9 CR cases were investigated for MRD by flow cytometry and all proved positive: 6/8 had MRD levels <10−3 in the PB and 2/8 in the BM. A progressive disease was recorded in 2 patients (4%) and a stable disease in 2 (4%). Six patients (11%) were not evaluable for response: 1 investigator's decision, 2 AEs (1 R infusion-related reaction and 1 unrelated episode of dyspnea) and 3 SAEs (1 CLB-related anemia, 1 endometrial in situ carcinoma and 1 anaplastic oligoastrocytoma). Seven SAEs occurred in 7 patients during courses 3–8. Only 1 SAE was related to treatment (1 CLB-related anemia). The most common toxicities were neutropenia (31.5% of patients, 8.9% of cycles) and thrombocytopenia (14.8% of patients, 5.7% of cycles). Grade III-IV neutropenia was present in 16.7% of patients and in 3.8% of cycles. No grade III-IV infections occurred. A median of 85.4 R-CLB courses was administered with 85.1% of patients completing the planned treatment; 15.3% of cycles needed a CLB dose reduction (12.9% due to toxicity, mainly neutropenia and thrombocytopenia). Conclusions: Overall, the results of the interim analysis indicate that R-CLB is active and well tolerated in elderly patients with previously untreated CLL. Disclosures: Foa: Roche: Consultancy, Speakers Bureau. Montillo: Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Runggaldier: Roche S.p.A. Monza: Employment. Gamba: Roche S.p.A. Monza: Employment.

An Open-Label Phase II Study to Investigate the Safety and Efficacy of Rituximab Plus Chlorambucil in Previously Untreated Patients with CD20-Positive B-Cell Chronic Lymphocytic Leukaemia (CLL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3428-3428 ◽  
Author(s):  
Peter Hillmen ◽  
John G. Gribben ◽  
George A Follows ◽  
Donald W. Milligan ◽  
Hazem A. Sayala ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Overall Response Rate ◽  
Response Rate ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Open Label ◽  
Overall Response ◽  
Binet Stage ◽  
The Uk

Abstract Abstract 3428 Poster Board III-316 Introduction Despite the increasing use of fludarabine (F) plus cyclophosphamide (C), and recently rituximab (R)-FC combinations in CLL, chlorambucil (Chl) remains a first-line treatment option, particularly for elderly patients and those with co-morbidities with chronic lymphocytic leukemia (CLL). However, rates of complete response (CR) are relatively low (up to 7%) as are overall responses (approximately 65%) with Chl. In this study we assessed the feasibility of adding R to Chl in order to improve outcomes. Methods Previously untreated patients with CLL who required therapy according to IWCLL criteria received R (day 1; 375 mg/m2 i.v. cycle 1, 500 mg/m2 cycles 2–6) plus Chl (days 1-7; 10mg/m2/day p.o.) repeated every 28 days for 6 cycles. A further 6 cycles of Chl alone was permitted in patients with continuing clinical response at 6 cycles. The primary endpoint was the adverse event (AE) profile. Secondary endpoints included response rates, progression-free and overall survival and assessment of minimal residual disease. Efficacy results from this study were compared with historical data from patients in the UK LRF CLL4 study who received Chl at the same dose but as monotherapy between 1999 and 2004. Each of the 50 patients in the Chl-R trial were matched to 3 patients from the CLL4 trial by Binet Stage (B or C), VH Mutation (mutated or unmutated), 11q FISH (deleted or not) and age. Results This is a planned interim analysis (IA) based on the first 50 patients out of the total 100 patients from 12 centres. Of these 47 patients were evaluable (2 missing bone marrow at time of IA; 1 protocol violation received only 1 cycle). The median age of patients was 70.5 years (range 48–86), 62% were male and 52% had Binet stage C CLL. The most common AEs were gastrointestinal disorders. There were 25 serious AEs (SAEs) reported in 17 patients. The most common SAEs were infections (10 SAEs, in 6 patients). Additionally there were 3 SAEs (in 3 patients) of febrile neutropenia – grade 3 or 4 neutropenia was reported in 40% of patients. Overall response rate on an intent-to-treat analysis was 84%. When compared with the well matched subset of Chl patients from the UK LRF CLL4 study, the overall response rate was 17.3% higher (95% CI 4.7% - 30.0%), indicating that the Chl-R patients have improved responses. Conclusions Based on this planned interim analysis, the addition of R to Chl is a feasible combination with no unexpected AEs. The combination of R and Chl was effective for untreated patients with CLL. It is important to note that the median age of patients in this study was considerably greater than the median age of patients in the UK LRF CLL4 and other large trials in CLL, and more representative of the typical age of patients presenting with CLL in the clinic. The combination of R and Chl was well-tolerated and effective for untreated patients with CLL who cannot tolerate a more intensive regimen, and suggest investigation in a Phase III study is warranted. Disclosures Hillmen: Alexion Pharmaceuticals: Consultancy; F.Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer Schering: Consultancy. Hayward:F.Hoffmann-La Roche Ltd: Former Employee.

Autologous Stem Cell Transplantation (ASCT) Versus Standard Treatments for CLL Patients: First Interim Analysis of a Prospective Randomized Study from the French Cooperative Study Group on CLL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5471-5471 ◽  
Author(s):  
Laurent Sutton ◽  
Marine Diviné ◽  
Philippe Travade ◽  
Claude Martin ◽  
Stéphane Leprêtre ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hemolytic Anemia ◽  
Interim Analysis ◽  
Response Rate ◽  
Randomized Study ◽  
Virus Reactivation ◽  
Cooperative Study Group ◽  
Mutational Status ◽  
Binet Stage ◽  
The Impact

Abstract Patients with stage B or C CLL, under 66 years, previously untreated are included in this trial. They are scheduled to receive 3 monthly courses of mini-CHOP (3mC) followed by 3 monthly courses of Fludarabine (3F) before evaluation of the response. Patients in complete response (NCI) undergo stem cells mobilisation with G-CSF alone, then are randomized between ASCT and observation. Patients not in CR receive 1 or 2 courses of DHAP for mobilisation of stem cells and are randomized between ASCT or 3 monthly courses of Fludarabine/Cytoxan (F/C). The primary endpoint in this study is EFS at 3 years. This first interim analysis was planed after the randomisation of the first 100 patients (6 October 2004). At that time, 142 patients have been included. Among them, 16 have not completed yet the full treatment before randomization; 26 were not randomized because of early death (9), erroneous inclusion (3), autoimmune hemolytic anemia (2), cytopenia (2), investigator’s or patient’s decision (10). From these 26 patients, 14 were nevertheless assessable for response after they received 3mC+3F (1 CR, 4 PR, 2 SD, 7 PD), 6 failed and 6 were not evaluable for response. For each included patient, cytology, flow cytometry, cyclin D1 expression and biological pronostic factors (cytogenetics, IgVH, mutational status, ZAP70 expression) were centrally reviewed. At baseline, 110 patients were in Binet stage B and 32 in Binet stage C. Median age at inclusion was 55 years (min: 31, max: 65). After the six monthly courses (3mC+3F), overall response (CR + PR) was 82.5% (99/120 patients); 49 patients were in CR (41%) from which 48 were randomized between observation and ASCT. 52 patients, not in CR, (46 PR, 5 SD, 1 PD) were randomized between ASCT and F/C. After randomisation, 9 patients died from refractory disease (6), pneumonia (3), neither after ABMT. Two patients had prolonged pancytopenia: one after ASCT who was further allografted and one after F/C. Four patients experienced a Richter syndrome, 3 before ASCT, 1 in the observation arm. Two patients developed hemolytic anemia (one after DHAP, one after the first course of F/C). One patient had hepatitis B virus reactivation 6 months after ASCT. This study is ongoing until randomization of 208 patients. These preliminary results show that in advanced stage CLL (B and C Binet stages) the 3mC+3F regimen displays a very good response rate, which compares favorably with the best published ones. The study of the impact of pronostic biological parameters on response rate is on progress and will be presented at the meeting.

Disruption of TP53 function by Point Mutations and Deletions Is Associated with An Increased Risk of Disease Progression within Previously Treated, Relapsed Chronic Lymphocytic Leukemia Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2445-2445
Author(s):  
Annika Dufour ◽  
Stefan K Bohlander ◽  
Evelyn Zellmeier ◽  
Gudrun Mellert ◽  
Karsten Spiekermann ◽  
...  
Keyword(s):  
Disease Progression ◽  
Research Funding ◽  
Tp53 Mutation ◽  
Lymphocytic Leukemia ◽  
Dominant Negative ◽  
Tp53 Mutations ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Binet Stage ◽  
Previously Treated

Abstract Abstract 2445 Chronic lymphocytic leukemia (CLL) patients with a deletion of the TP53 tumor supressor gene located at 17p13 have a poor prognosis in first line chemotherapy regimens. Recent studies indicated somatic TP53 mutations as a prognostic factor in CLL independent of 17p13 deletion status. We aimed to further characterize the prognostic value and the impact of TP53 mutations on progression-free survival (PFS) in the presence and absence of a 17p13 deletion in previously treated and relapsed CLL patients within an international phase III clinical study comparing Fludarabine and Cyclophosphamide with or without Rituximab (FC versus R-FC: REACH trial). We analyzed 457 patients at diagnosis for mutations in the TP53 gene using a combination of a microarray-based resequencing assay (AmpliChip p53 Test, Roche Molecular Systems, USA.) and Sanger sequencing of TP53 exons 2–10. The data were correlated with clinical and biologic markers as well as with interphase fluorescence in situ hybridization (FISH) and with PFS. Association of the clinical data with PFS was assessed by Cox proportional hazard models. To estimate the functional significance of the individual TP53 mutations we used the IARC TP53 database. TP53 mutations (n=60) were detected in 52 of 457 patients (11.4%) and included 42 missense, 4 nonsense, 8 frameshift mutations, 2 in-frame deletions and 4 mutations in splice sites. Among other clinical variables, only 17p13 deletion was associated with TP53 mutations: 27 of 52 TP53 mutated patients had a 17p13 deletion (concordance rate: 52%, Fisher's test p<0.001). Median PFS for patients with TP53 mutations (n=52, 13 months, HR=1.9 (1.4–2.7), p<0.001) was significantly shorter as compared to patients without TP53 mutations (n=480, 27 months). In a sub-group analysis, chemoimmunotherapy including Rituximab did not significantly improve the PFS of patients with TP53 mutations. Multivariate analysis including treatment arm, Binet stage, age, IGVH mutational status, 17p13 deletion and TP53 mutation status confirmed TP53 mutation status (HR-TP53=1.7 (1.1–2.6), p=0.009) as a prognostic factor for PFS independent of 17p13 deletion status (HR-17p=1.7 (1.1–2.7), p=0.024) and with a similar effect size. The other independent prognostic factors were treatment (HR=0.61 (0.48–0.76), p<0.001), Binet stage (HR=1.64 (1.3–2.1), p<0.001) and IGVH mutational status (HR=2.4 (1.85–3.1), p<0.001). To further dissect the contribution of TP53 mutation and 17p13 deletion on PFS, we considered a multivariate analysis comparing patients with both TP53 mutation and 17p13 deletion (n=28), with only 17p13 deletion (n=9), with a dominant negative TP53 mutation or multiple TP53 mutations (n=8) or with a single TP53 mutation (n=16) against patients without TP53 abnormalities (n=271), adjusted for treatment, Binet stage, age and IGVH mutational status. Patients with a predicted biallelic disruption of TP53 either by a TP53 mutation in combination with a 17p13 deletion (HR: 2.8 (1.8,4.2), p=<0.001) or patients with a dominant negative TP53 mutation as predicted by the IARC TP53 database or multiple TP53 mutations (HR=3.26 (1.5,7.1), p=0.003) had a risk similar in size and which was quite high for disease progression (the reference to calculate the risk, here and in the following, is always the group of patients without TP53 abnormalities). The risk slightly decreased for patients with only a deletion 17p13 (HR=2.2, (1.1–4.3), p=0.021). Very interestingly, single TP53 mutations showed a much lower risk for disease progression (in this case not even significant) (HR=1.61 (0.9–2.8), p=0.084) especially compared to the risk conferred by a biallelic disruption. In this large cohort of previously treated CLL patients, complete disruption of TP53 function (by a combination of a 17p13 deletion and a TP53 mutation, through dominant negative TP53 mutations or through multiple TP53 mutations) was associated with a higher risk for disease progression. Prognosis of patients with a single TP53 mutation was not significantly different from patients without TP53 aberrations. It remains to be shown whether CLL patients with a single TP53 mutation are at a higher risk of acquiring additional mutations of TP53 during disease progression. Prognostic stratification of previously treated CLL patients should include a routine molecular TP53 mutational analysis in addition to deletion analysis of the TP53 locus by FISH. Disclosures: Dufour: Roche: Research Funding. Bohlander:Roche: Research Funding. Spiekermann:Roche: Research Funding. Schneider:Roche: Research Funding. Hiddemann:Roche: Research Funding. Truong:Roche: Employment. Patten:Roche: Employment. Wu:Roche: Employment. Dmoszynska:Mundipharma:; Roche: Honoraria. Robak:Centocor Ortho Biotech Research & Development: Research Funding. Geisler:Roche: Speakers Bureau. Dornan:Genentech: Employment. Lin:Genentech: Employment. Yeh:Genentech: Employment. Weisser:Roche: Employment. Duchateau-Nguyen:Roche: Employment. Palermo:Roche: Employment.

scholarly journals Metronomic Chemotherapy Is Effective and Well Tolerated in Relapsed/Refractory Elderly Patients with Aggressive B- and T-Cell Lymphomas

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5080-5080
Author(s):  
Maria Christina Cox ◽  
Elena Cavalieri ◽  
maria Paola Bianchi ◽  
Raffaele Porrini ◽  
Virginia Naso ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Elderly Patients ◽  
Overall Response Rate ◽  
Hospital Admissions ◽  
Response Rate ◽  
Induction Phase ◽  
Overall Response ◽  
T Cell Lymphomas ◽  
Grade 3

Abstract BACKGROUND: Elderly patients with Relapsed/Refractory (R/R) aggressive Large B-cell lymphoma (LBCL) and Peripheral T-cell lymphomas (PTCL), are commonly treated with intravenous conventional chemotherapies, which are often poorly tolerated and of short-lasting efficacy. Therefore only few fit-elderly patients might undergo intensive treatments with curative intent. Metronomic chemoterapy (MTN-CHT) is a new way of administering old drugs at low doses with only short chemotherapy free intervals. MTN-CHT may be combined with new targeted molecules, immunotherapies and radiotherapy. Although very few reports on MTN-CHT in LBCL and PTCL have been published existing data suggest that these lymphomas might respond to this approach. AIM: We aimed at demonstrating the efficacy and safety of MTN-CHT in a retrospective series of elderly patients with LBCL and PTCL, unfit for conventional treatments. PATIENTS AND TREATMENTS: From October 2008 up to May 2015 we treated elderly patients with R/R LBCL, Follicular Lymphoma(FL) and PTCL with MTN-CHT based regimen. Eligible patients should have given written informed consent, have a Performance Status=0-3, a life expection >2 months, be able to take oral therapy and have a care-giver. We used three different MTN schedules: 1] Provecip; 2] Vinblastine+Endoxan+Etoposide+Prednisone (VEED) and in the last two years an all-oral schedule 3] Navelbine+Endoxan+Etoposide+Prednisone (DE-VEC). All three schedules of MTN-CHT consisted of an induction phase of six months followed by a maintenance phase administered until progression or excessive toxicity. Rituximab was added to the induction phase for those patients characterized by CD20 expression. Thrombosis prophylaxis was carried out with aspirin or LMWH. RESULTS Patients features: LBCL=21; PTCL=7, FL=3; Age=77y (median, range 62-90), Previous CHT=2 (median, range 0-5) refractory to last CHT= 43%. MTN-CHT: 8 pts were treated with schedule 1], 8 pts with schedule 2] and 15 pts with schedule 3]. Outcome: in aggressive B and T-cell lymphomas (n=28pts) with all schedules Overall Response Rate = 62%, Complete Remission rate = 36%; Progression Free Survival = 8 months, Median Duration of Response (DOR)= 10 months. Overall Response Rate and Complete Remission in the subset treated with the all-oral DE-VEC schedule were 66% and 50% respectively. Serious adverse events: Extra hematologic toxicity grade 3-4: pulmonary embolism in 1pts; hematological toxicity of grade 3-4 and/or neutropenic infections in 6 patients 5 of whom had >2 previous conventional chemotherapies. The use of DE-VEC all-oral schedule reduced the number and the durations of day-hospital admissions. CONCLUSION Although our series is limited, these results suggest that MTN-CHT in elderly patients with R/R LBCL, PTCL and FL might achieve favorable results in terms of activity, toxicity and costs due to hospital admissions. With MTN-CHT most of the patients did not need G-CSF. Notably, patients who had had >2 lines of chemotherapies may be at very high risk of prolonged cytopenia and infections during MTN-CHT. Since the all-oral DE-VEC schedule was particularly manageable and active we believe that this combination deserve further investigation in aggressive lymphomas. Disclosures No relevant conflicts of interest to declare.

MicroRNA-29c and 223 Are Powerful Prognostic Factors for Chronic Lymphocytic Leukemia and Improve Risk Stratification When Combined with ZAP70 and LPL in a qPCR Score.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1066-1066
Author(s):  
Basile Stamatopoulos ◽  
Nathalie Meuleman ◽  
Dominique Bron ◽  
Benjamin Haibe-Kains ◽  
Pascale Saussoy ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Early Therapy ◽  
Mutational Status ◽  
Igvh Mutational Status ◽  
Binet Stage

Abstract Background: MicroRNAs (or miR) are a novel class of small noncoding RNA involved in gene regulation. Aberrant microRNA expression has been recently associated with chronic lymphocytic leukemia (CLL) outcome. Currently, the heterogeneous evolution of this disease can be predicted by several prognostic factors. Nevertheless, a better individualization of the outcome in a given patient is still of utmost interest. Methods: In the current study, we investigated the expression of two microRNAs, miR-29c and miR-223, compared them to other biological or clinical markers and proposed a quantitative real-time PCR (qPCR) score to better assess CLL outcome. All cut-offs were calculated by ROC curve analysis maximising the correlation with the immunoglobulin variable heavy chain (IgVH) mutational status; statistical differences were evaluated by Mann Whitney test or Kruskal-Wallis test ; treatment-free (TFS) and overall (OS) survival differences were investigated by log-rank test or Cox proportional hazard ratio (HR). Results: miR-29c and miR-223 expression decreased significantly with progression along Binet Stage A to C (P=0.0010 and P=0.0183, respectively), and were significantly lower in poor prognosis subgroups defined by cytogenetic abnormalities, IgVH mutational status, lymphocyte doubling time, solubleCD23, β2-microglobulin, ζ-associated protein 70 (ZAP70), lipoprotein lipase (LPL) and CD38 expression. Furthermore, miR-29c and miR-223 could predict TFS (n=110, P=0.0015 and P&lt;0.0001, respectively) and OS (n=110, P=0.0234 and P=0.0008, respectively). Regarding all these results, we developed a qPCR score (from 0 to 4 poor prognostic markers) combining miR-29c, miR-223, ZAP70 and LPL in order to stratify treatment and death risk in a 110 patient cohort with a median follow-up of 72 months (range, 2–312). Patients with a score of 0/4, 1/4, 2/4, 3/4, and 4/4 had a median TFS of &gt;312, 129, 80, 36 and 19 months, respectively (HR=17.00, P&lt;0.0001). Patient with a score of 0–1/4, 2–3/4 and 4/4 had a median OS of &gt;312, 183 and 106 months, respectively (HR=13.69, P=0.0001). Interestingly, during the first 50 months after diagnosis, only 10% of patients with a 0/4 score required a treatment, when compared to 100% of the 4/4. Furthermore, during the total follow-up (312 months), patients with a 4/4 score had a 27-fold higher risk to be treated and a 31-fold higher risk to die comparing to patients with a 0/4 score. This score was validated by a 10-fold cross-validation (prediction accuracy of 82%). Finally, in Binet stage A patients (n=77), this score remained relevant and significant for TFS and OS prediction (HR=18.56, P&lt;0.0001 and HR=12.5, P=0.0068, respectively). Conclusions: we showed that (i) miR-29c and miR-223 levels were decreased in poor prognosis patients regarding several well-known prognostic factors; (ii) a low level of these two microRNAs is thus associated to disease aggressiveness, tumor burden and poor clinical evolution; (iii) we also showed that these two microRNAs could predict TFS and OS; (iv) we proposed a qPCR score to better individualize evolution of a particular CLL patient. This score will help to identify patients who will need early therapy and require thus a closer follow-up.

scholarly journals Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5799-5802 ◽  
Author(s):  
Claire E. Dearden ◽  
Amit Khot ◽  
Monica Else ◽  
Mike Hamblin ◽  
Effie Grand ◽  
...  
Keyword(s):  
T Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Rescue Therapy ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Prolymphocytic Leukemia ◽  
Free Survival ◽  
Median Progression Free Survival

Abstract Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell prolymphocytic leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab. The UKCLL05 pilot study examined the efficacy and toxicity of this more convenient method of administration in 9 previously untreated patients with T-PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results. After rescue therapy with intravenous alemtuzumab and/or pentostatin, median progression-free survival and overall survival were similar to the intravenous group. Alemtuzumab delivered intravenously, but not subcutaneously, remains the treatment of choice for previously untreated T-PLL. This study is registered at www.eudract.ema.europa.eu as #2004-004636-31.

Real-world overall response rate and other outcomes related to originator and biosimilar rituximabin patients with chronic lymphocytic leukemia or non-Hodgkin’s lymphoma in the United Kingdom.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18696-e18696
Author(s):  
Ali McBride ◽  
Shoshana Daniel ◽  
Maurice T. Driessen ◽  
Agota Szende ◽  
Azhar Choudhry ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Patient Outcomes ◽  
Real World ◽  
Overall Response Rate ◽  
Response Rate ◽  
Healthcare Resource ◽  
Healthcare Resource Utilization ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Grade 3

e18696 Background: Rituximab is a chimeric anti-CD20 monoclonal antibody therapy, used primarily for treating chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Rituximab-abbs, the first rituximab biosimilar, was approved in the UK in 2017 and was expected to significantly reduce drug acquisition costs, but there is a lack of real-world evidence regarding patient outcomes with rituximab-abbs. This non-interventional study assessed the real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. Methods: Anonymized data on patient characteristics, response to treatment, healthcare resource utilization and costs were abstracted retrospectively via an online physician survey. UK-registered hematologists and oncologists reported on randomly selected patients aged ³18 years from four cohorts with documented CLL or NHL, who had received rituximab-abbs or rituximab as first-line immunotherapy (between January 1, 2018 and June 30, 2019). Patient outcomes data were provided from first treatment to the last date of follow-up available in the medical records. Results: In total, 46 physicians abstracted data from 201 patient charts. Demographic profiles of the cohorts were similar. For both treatments, the overall response rate (ORR) was very high for patients with CLL or NHL (Table) along with rates for six-month progression-free survival (96–98% across cohorts) and one-year survival (98–100% across cohorts). Most patients did not experience a grade ≥3 adverse event during treatment (54–66% across cohorts); the most common grade ≥3 adverse events were neutropenia, fatigue, anemia and infusion reactions. Healthcare resource utilization was similarly high across cohorts, driven by drug costs, diagnostic testing, oncologist office visits, and day case hospital admissions. Mean annual savings of approximately £1,000 per patient were seen with rituximab-abbs, attributable to first-line treatment costs. Conclusions: The originator (rituximab) and biosimilar (rituximab-abbs) products yielded comparable efficacy and tolerability in treating CLL and NHL in routine UK clinical practice, with rituximab-abbs demonstrating cost-savings. These findings should inform decision-makers on the potential for cost reductions where the biosimilar rituximab-abbs is available as a treatment alternative.[Table: see text]

17p Deletion Predicts for Inferior Overall Survival after Fludarabine - Based First Line Therapy in Chronic Lymphocytic Leukemia: First Analysis of Genetics in the CLL4 Trial of the GCLLSG.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 715-715 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Alexander Kröber ◽  
Raymonde Busch ◽  
Barabara Eichhorst ◽  
Dirk Kienle ◽  
...  
Keyword(s):  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Mutation Status ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Genomic Aberrations

Abstract The CLL4 trial evaluated first line treatment with fludarabine (F) or F + cyclophosphamide (FC) among 375 CLL patients up to 65 years enrolled between 1999 and 2003. FC resulted in a higher overall response rate (94% vs. 83%; P=0.001), longer median progression free survival (PFS) (48 vs. 20 months (m); P=0.001), but no difference in overall survival (OS) (Eichhorst et al., ASH 2003 and submitted). At enrollment, genomic aberrations and the VH mutation status have been analyzed for 307 and 280 cases thus far. The most frequent genomic aberrations were 13q-: 50.3%, 13q- single: 34.1%, 11q-: 20.3%, +12q: 13.7%, 6q-: 8.7%, 14q-: 6.1%, and 17p-: 4.9%. VH was mutated in 33.9% and unmutated in 66.1% of cases. The aberrations 13q- and 13q- single were more frequently observed in the VH mutated subgroup (45.4% vs. 32.7% and 35.5% vs. 18.8%, respectively), while 11q- (26.9% vs. 12.2%) and 6q- (14.2 vs. 1.7%) were more common in the VH unmutated subgroup. Clinical outcome was evaluated in subgroups defined by genomic aberrations and VH status for both treatment arms combined. In univariate analyses, significant associations were found for the following parameters: the overall response rate was significantly lower in the subgroup with 17p- (53.8% vs. 89.6%, P=0.001), the median PFS was significantly shorter in the subgroups with 11q- (17.4 vs. 26.8 m, P=0.044), 14q- (14.5 vs. 24.5 m, P=0.018), and 17p- (11.0 vs. 24.1 m, P=0.002), and the median OS was significantly shorter in the subgroup with 17p- (15.9 m vs. not reached, 75% survival at 43.8 m, P&lt;0.001, Figure 1). Multivariate analysis was performed including the treatment arms, specific genomic aberrations, and the VH mutation status as possible prognostic factors: the parameters with significant adverse impact were F monotherapy (HR 1.70, 95%CI 1.12-2.58, P=0.013) and 17p- (HR 3.67, 95%CI 1.66-8.14, P=0.001) regarding PFS, but only 17p- (HR 7.32, 95%CI 2.44-21.90, P&lt;0.001) regarding OS. In conclusion, this first analysis of the prospective CLL4 trial shows that 17p- CLL is characterized by a short OS after F-based first line therapy. In future trials, alternative primary treatment strategies of proven efficacy in 17p- CLL such as alemtuzumab should be considered for these patients. Figure Figure

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