scholarly journals Comparative Evaluation of Ibrutinib in Treatment of Chronic Lymphocytic Leukemia Using Simulation Modeling

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1299-1299
Author(s):  
Siyang Peng ◽  
Feng Pan ◽  
Sonja Sorensen ◽  
Emily Dorman ◽  
Yingxin Xu ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Sample Size ◽  
Simulation Modeling ◽  
Patient Characteristics ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Significant Heterogeneity ◽  
Bulky Disease

Abstract Background Treatment options for chronic lymphocytic leukemia (CLL) patients who received prior therapy are limited, especially for patients in high risk categories, such as del 17p; new therapies are urgently needed. In the Phase III RESONATE (Byrd, 2014), single agent ibrutinib, an oral, once-a-day, first-in-class covalent Bruton's tyrosine kinase inhibitor, was associated with improved progression-free survival (PFS, HR=0.215), overall survival (OS, HR=0.387) and overall response rate (ORR, 63% vs. 4%) compared with ofatumumab alone. Here we assessed the availability and comparability of clinical data for key therapies used in pre-treated CLL patients with ibrutinib and project long-term outcomes of ibrutinib for comparable studies using a simulation model. Methods A systematic literature review (SLR) identified relapsed or refractory CLL clinical trials on the following regimens: bendamustine ± rituximab (BR), fludarabine + cyclophosphamide + rituximab (FCR), ofatumumab, idelalisib + rituximab (IR), and rituximab. Patient populations and outcomes (ORR, PFS, and OS) were compared. A health state model was then developed to simulate long-term PFS and OS, comparing other therapies with ibrutinib. The model simulated treatment of a cohort of patients with pre-treated CLL until death or until disease progression, at which point they were simulated to receive subsequent treatment or best supportive care. Available Kaplan-Meier data were used to estimate longer-term projections of PFS and OS of comparable trials. Results The SLR identified few (n=36) relevant trials, only 4 of which were RCTs; comparison to ibrutinib through a common comparator was not possible. Pivotal trials was identified for each therapy based on the comparability to the RESONATE population, largest sample size and greatest amount of data reported. Selected trials (Table) showed significant heterogeneity between study populations, including variations in adverse cytogenetics (e.g. del 17p, del 11q), treatment line, and other characteristics (e.g. bulky disease) which have important ramifications on health outcomes. Three trials were excluded from simulation modeling: Robak (FCR) and LeBlond (BR) consisted of less heavily pre-treated patients than RESONATE; Furman et al. 2014 (rituximab and idelalisib+rituximab), enrolled a similar population to RESONATE aside from 17 p del, however, long-term safety and efficacy outcomes are limited due to the short follow-up in the idelalisib trial. Simulation over a 10 year horizon resulted in prolonged estimated mean OS for ibrutinib compared to ofatumumab (66 months versus 39 months). Despite the ibrutinib patients consisting of more heavily pre-treated, worse adverse cytogenetics and high risk features than those included in the BR and FCR studies, naïve comparison of long-term OS was projected to be 26 months and 8 months longer with ibrutinib respectively. Conclusion Comparisons of outcomes across trials are inherently limited by differences in populations, trial designs, and measurements. In this limited, naïve comparison of high risk CLL patients, ibrutinib is reasonably expected to provide incremental OS over BR and FCR in the pre-treated CLL setting, even when considering the RESONATE patient population included more heavily pre-treated patients and those with worse cytogenetics. The most rigorous comparison, using comparative data from a head-to-head trial, indicated that ibrutinib significantly prolonged PFS and OS compared to ofatumumab, which has established activity in hard-to-treat patients. Table. Patient Characteristics Patient Characteristics RESONATE RESONATE Fischer Badoux Furman Furman Robak FCR LeBlond BR Ibrutinib Ofatumumab BR FCR Rituximab + placebo Rituximab + idelalisib Sample Size 195 196 78 284 110 110 276 58 Median age (range) 67(30- 88) 67 (37- 88) 66.5 (42-86) 60 (NA) 71 (47-92) 71 (48- 90) 63 (35-83) 75 (49-87) Del 17p, (%) 32.30% 32.70% 19.20% 7% 28.20% 23.60% 7% 12% Median # of prior therapies (range) 3 (1-12) 2 (1-13) 2 (1-5)* 2 (1-10) 3 (1-9) 3 (1-12) 1 (1-1) 1 (1-2) % ≥3 prior therapies 52.80% 45.90% 43% 31% NA NA 0% 0% % Purine analog refractory 44.60% 44.90% 28.2%~ 19%~ NA NA NA NA Disclosures Peng: Janssen: Consultancy; Evidera: Employment. Pan:Janssen: Consultancy; Evidera: Employment. Sorensen:Evidera: Employment; Janssen: Consultancy. Dorman:Janssen: Consultancy; Evidera: Employment. Xu:Janssen: Consultancy; Evidera: Employment. Sallum:Evidera: Employment; Janssen: Consultancy. Gaudig:Janssen: Employment. Sengupta:Janssen: Employment. Wildgust:Janssen Global Services: Employment. Sun:Janssen: Employment.

Long-term results of the Polish Adult Leukemia Group PALG-CLL2 phase III randomized study comparing cladribine-based combinations in chronic lymphocytic leukemia

2013 ◽  
Vol 55 (3) ◽  
pp. 606-610 ◽  
Author(s):  
Tadeusz Robak ◽  
Jerzy Z. Blonski ◽  
Joanna Gora-Tybor ◽  
Malgorzata Calbecka ◽  
Jadwiga Dwilewicz-Trojaczek ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Randomized Study ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Long Term Results ◽  
Adult Leukemia ◽  
Leukemia Group

Effect of adding ublituximab to ibrutinib on PFS, ORR, and MRD negativity in previously treated high-risk chronic lymphocytic leukemia: Final results of the GENUINE phase III study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8022-8022 ◽  
Author(s):  
Jeff P. Sharman ◽  
Danielle M. Brander ◽  
Anthony R. Mato ◽  
Nilanjan Ghosh ◽  
Stephen J. Schuster ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
First Year ◽  
Bulky Disease ◽  
Depth Of Response ◽  
Independent Review ◽  
Secondary Endpoints ◽  
Anti Cd20

8022 Background: The BTK inhibitor ibrutinib (IB) has advanced the treatment for patients (pts) with CLL, however, among pts with high-risk CLL, disease control with IB is less durable. Ublituximab (UTX) is a glycoengineered mAb with enhanced ADCC. The GENUINE study evaluated the addition of UTX to IB vs. IB alone in high-risk rel/ref CLL. With a median follow up now 3.5+ yrs, we present the final results. Methods: Eligible pts having rel/ref CLL with centrally confirmed del17p, del11q, and/or a TP53 mutation, were randomized 1:1 to IB (420 mg QD) alone or with UTX (900 mg on D1, 8, 15 of Cy 1, D1 of Cy 2-6, and Q3 Cy thereafter). No limit on # of prior Tx; prior IB excluded. Primary endpoint was overall response rate (ORR) by iwCLL 2008 (excludes PR-L); secondary endpoints were CR rate, peripheral blood MRD negativity (analyzed centrally), PFS, and safety. Response was by blinded independent review. Results: 117 pts were treated (59 in UTX + IB arm; 58 in IB arm). Med age was 66 yrs and med # of prior Tx was 1 (range 1-5) for each arm. Baseline features were relatively balanced including ECOG, gender, and med time since diagnosis (6+ yrs). 17p del was greater in the IB arm (50% vs 44%); bulky disease was greater in UTX + IB arm (47% vs 28%); IGHV-unmut was 83% for both arms. At data-cutoff of Sep 1, 2019, AEs were comparable between the arms, except infusion reactions (UTX + IB: All G 53% / G 3/4 3%) and neutropenia (All G 36% vs 21%, G 3/4 19% vs. 12%) which were higher for UTX + IB. At a med follow up of 42 mos, all efficacy endpoints were in favor of UTX + IB (see Table). Conclusions: In contrast to prior studies adding rituximab to IB, GENUINE is the first randomized trial to demonstrate a PFS benefit with the addition of an anti-CD20 to IB. Increasing depth of response (CR rate, MRD-neg) post first year of Tx supports maintenance therapy with UTX. Clinical trial information: NCT02301156 . [Table: see text]

Eradication of Minimal Residual Disease Using Alemtuzumab Consolidation After High-Dose Methyl-Prednisolone Plus Rituximab (HDMP-R) Is Safe, Effective and Induces Long Term Remission in Chronic Lymphocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2866-2866
Author(s):  
Januario E. Castro ◽  
Lina M. Ariza-Serrano ◽  
Juan S. Barajas-Gamboa ◽  
Julio A. Diaz-Perez ◽  
Danelle F. James ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Bulky Disease ◽  
Minimal Residual

Abstract Abstract 2866 Despite advances in the treatment of patients with chronic lymphocytic leukemia (CLL), the disease still remains incurable and eradication of minimal residual disease (MRD) being one of the most challenging goals of treatment. Alemtuzumab (Campath-H1™) has been shown to effectivily eradicate MRD from the bone marrow and induce long-term remissions, however its use is limited to patients without bulky disease. Futhermore, combination of alemtuzumab with chemotherapy has resulted in serious adverse events. In this study, we evaluate the toxicity and efficacy of alemtuzumab as consolidation therapy for CLL patients following induction with high-dose methylprednisolone in combination with rituximab (HDMP-R). Twenty-one patients with evidence of residual disease after treatment with HDMP-R received additional treatment with alemtuzumab. This antibody was administered three times a week for a total of 8 weeks. Patients received antibiotic prophylaxis with trimethoprim-sulfamethoxazole 160/800 mg twice a day × 3 per week, fluconazole 100 mg / day and valganciclovir 900 mg / day. The median age was 60 years (range, 49–73), with Rai stage III-IV in 81% of the patients. Twelve patients (57%) had evidence of unmutated IgVH gene and thirteen (62%) had high level of ZAP-70 expression. Cytogenetic and FISH analysis showed eight patients with deleletion 13q, three patients with trisomy 12, one patient with deletion 11q, five patients with no chromosomal abnomalities and in six patients data was not available. The median number of previous treatments was 1.3 (range, 0–5) and the median time from the end of HDMP-R treatment to initiation of alemtuzumab was 5 months (range, 1–14). After HDMP-R, nine patients (43%) achieved CR and twelve (57%) were in PR; all of them had evidence of residual disease in the bone marrow by 4-color flow cytometry analysis. Eight additional patients achieved CR after consolidation with alemtuzumab for a total of 17 patients (81%) in CR at the end of the study. We found no evidence of MRD (MRDneg) in 12 of those patients (57% of the total and 71% of CR patients). Of the remaining patients, one had PR and three patients had progressive disease for an overall response rate of 86%. The median progression-free survival (PFS) was 63 months (range, 6–84) for all patients. The median PFS in CR MRDneg patients has not been reached at a median follow-up of 46 months (range, 18–84), with 8/12 patients that have not progressed after a time at risk of 3.8 years. CR MRDpos patients have a median PFS of 48 months (range, 6–48). The treatment was well tolerated and there were no deaths attributed to therapy. Adverse events were classified following the NCI common terminology criteria for adverse events (CTCAE) Version 4.0. Two patients (9.5%) developed infections. The first event occurred during the administration of alemtuzumab and required hospitalization of the patient for management of pneumonia galactomannan positive suspicious for invasive aspergillosis (Grade 3), the second event was in a patient with aspegillus sp. infection of the skin that occurred four months after completion of alemtuzumab (Grade 2). Both patients recovered completely. We observed no CMV or other opportunistic infections. Three patients (14%) developed cytopenias; two patients with (Grade 4) thrombocytopenia and three patients with (Grade 4) neutropenia. In conclusion, alemtuzumab consolidation for residual disease after treatment with HDMP-R was well tolerated and effective in patients with CLL. We observed a near two-fold increase in the number of patients that achieved CR and the majority of these (71%) had no evidence of MRD. Moreover, patients with CR MRDneg have an exceptionally long PFS. The low rate of infection and lack of treatment related mortality compares very favorably with previous studies using alemtuzumab consolidation after chemotherapy treatment in which toxicities including treatment related death were found to be prohibitive. These encouraging results provide the rationale for additional studies using this combination therapy. Disclosures: James: Celgene: Research Funding.

scholarly journals The Difficult-to-Treat del 17 p Patient—A Case Report in Chronic Lymphocytic Leukemia

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 33
Author(s):  
Ana-Maria Moldovianu ◽  
Ana Manuela Crisan ◽  
Zsofia Varady ◽  
Daniel Coriu
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Risk Patients ◽  
Potential Benefits

Chronic lymphocytic leukemia (CLL) treatment strategies have evolved to include mechanism-driven drugs but now raise new questions regarding their optimum timing and sequencing. In high-risk patients, switching from pathway inhibitors to allogeneic stem cell transplantation (allo-HCT) is still a matter of intense debate. We report the case of a CLL patient with 17 p deletion treated with ibrutinib as a bridge to allo-HCT. Early relapse after allo-HCT urged the initiation of salvage therapy, including donor lymphocytes infusions, ibrutinib, and venetoclax. We aim to outline and discuss the potential benefits of novel therapies, the current role of allo-HCT in CLL, drug timing and sequencing, and the unmet need to improve the long-term outcome of high-risk CLL patients.

Dinaciclib (SCH 727965) Is a Novel Cyclin-Dependent Kinase (CDK) Inhibitor That Exhibits Activity In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 871-871 ◽  
Author(s):  
Joseph M. M. Flynn ◽  
Leslie A. Andritsos ◽  
Jeffrey A. Jones ◽  
Amy J. Johnson ◽  
Kami Maddocks ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Dose Level ◽  
Dose Escalation ◽  
Lymphocytic Leukemia ◽  
Cyclin Dependent Kinase ◽  
Bulky Disease ◽  
Tumor Lysis ◽  
High Risk Disease ◽  
Initial Starting

Abstract Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults. While the breadth of therapies for this incurable disorder has increased recently, patients afflicted with high risk disease have few and predominantly unsatisfactory options. Cyclin-dependent kinase (CDKs) inhibitors, such as Flavopiridol, have demonstrated clinical activity in CLL, though have been associated with significant therapy associated tumor lysis (TLS). Dinaciclib is a selective inhibitor of CDKs 1, 2, 5, and 9 that exhibits activity in CLL, including high risk subtypes. We performed a phase 1 dose escalation trial in relapsed and refractory CLL in order to determine the recommended phase 2 dose and maximum administered dose of dinaciclib. Patients received treatment as a 2-hour IV infusion on days 1, 8 and 15 of a 28-day cycle. The initial starting dose, determined based on preclinical data, was 5 mg/m2. Other dosing cohorts of 7 mg/m2, 10 mg/m2, 14 mg/m2 and 17mg/m2 were included in the dose escalation schema. An expansion cohort of patients utilizing an intra-patient dose escalation of 7mg/m2 on day 1, 10mg/m2 on day 8 and 14mg/m2 on day 15 during cycle 1 and 14mg/m2 on days 1, 8, and 15 of each subsequent cycle was further employed. Patients continued on treatment until there was disease progression, unacceptable toxicity or subject’s refusal to continue. In total, 52 patients have been enrolled on this trial. The median age is 62.4 years (range 43-79), with 46% of patients ≥65 years. The majority of patients have advanced Rai stage (65%) and/or bulky disease (69%) and 46% with del(17p13.1). The median number of prior therapies is 4 (range 1-12) with 92% having received prior fludarabine and 31% having received prior flavopiridol. One episode of a dose limiting toxicity (DLT) was noted at 7mg/m2 (sepsis/death) and two at dose level of 17mg/m2 (hyperacute tumor lysis syndrome and pneumonia). One further DLT of TLS occurred at the recommended phase II dose level of 14mg/m2 during cohort expansion for a total of 18 patients treated at 14mg/m2. The most common serious adverse events included leucopenia, anemia, thrombocytopenia and metabolic evidence of tumor lysis, which occurred in 15% of patients. Clinical response was assessed utilizing the 1996 NCI-WG CLL criteria. The overall response rate of evaluable patients was 58% (28 of 48), while 57% patients with del(17p13.1) and 63% with del(11q22) achieved at least a partial response. The median progression free survival was 481 days (95% CI, 253 – 481). For responders, the median treatment duration was 214.5 days (range, 79 – 470 days). In conclusion, Dinaciclib is clinically active in this population of relapsed and refractory CLL. Importantly, patients with high risk disease, such as del(17p13.1) demonstrated impressive overall responses. Utilizing a dose escalation treatment model, Dinaciclib is well tolerated, safe and associated with typical toxicities which are readily managed. The use of this agent in combination with other efficacious agents, especially in the high risk CLL population is warranted. Disclosures: Jones:Pharmacyclics: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Small:Merck: Employment. Im:Merck: Employment. Zhou:Merck: Employment.

scholarly journals Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia

2019 ◽  
Vol 37 (16) ◽  
pp. 1391-1402 ◽  
Author(s):  
Jeff P. Sharman ◽  
Steven E. Coutre ◽  
Richard R. Furman ◽  
Bruce D. Cheson ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Extension Study ◽  
Efficacy And Safety ◽  
Term Efficacy ◽  
Phase Iii Study ◽  
Grade 3 ◽  
To Receive

PURPOSE A randomized, double-blind, phase III study of idelalisib (IDELA) plus rituximab versus placebo plus rituximab in patients with relapsed chronic lymphocytic leukemia (CLL) was terminated early because of superior efficacy of the IDELA-plus-rituximab (IDELA/R) arm. Patients in either arm could then enroll in an extension study to receive IDELA monotherapy. Here, we report the long-term efficacy and safety data for IDELA-treated patients across the primary and extension studies. PATIENTS AND METHODS Patients were randomly assigned to receive rituximab in combination with either IDELA 150 mg twice daily (IDELA/R; n = 110) or placebo (placebo/R; n = 110). Key end points were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety. RESULTS The long-term efficacy and safety of treatment with IDELA was assessed in 110 patients who received at least one dose of IDELA in the primary study, 75 of whom enrolled in the extension study. The IDELA/R-to-IDELA group had a median PFS of 20.3 months (95% CI, 17.3 to 26.3 months) after a median follow-up time of 18 months (range, 0.3 to 67.6 months). The ORR was 85.5% (94 of 110 patients; n = 1 complete response). The median OS was 40.6 months (95% CI, 28.5 to 57.3 months) and 34.6 months (95% CI, 16.0 months to not reached) for patients randomly assigned to the IDELA/R and placebo/R groups, respectively. Prolonged exposure to IDELA increased the incidence of all-grade, grade 2, and grade 3 or greater diarrhea (46.4%, 17.3%, and 16.4%, respectively), all-grade and grade 3 or greater colitis (10.9% and 8.2%, respectively) and all-grade and grade 3 or greater pneumonitis (10.0% and 6.4%, respectively) but did not increase the incidence of elevated hepatic aminotransferases. CONCLUSION IDELA improved PFS and OS compared with rituximab alone in patients with relapsed CLL. Long-term IDELA was effective and had an expected safety profile. No new IDELA-related adverse events were identified with longer exposure.

scholarly journals Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia

Medicina ◽  
2019 ◽  
Vol 55 (11) ◽  
pp. 719
Author(s):  
Pileckyte ◽  
Valceckiene ◽  
Stoskus ◽  
Matuzeviciene ◽  
Sejoniene ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Meaningful Improvement ◽  
Free Survival ◽  
High Dose Methylprednisolone ◽  
Unfit Patients

Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10–12). Median OS was 68 (range 47–89) months. Adverse events (AE) were mainly grade I–II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588).

scholarly journals Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 399-404 ◽  
Author(s):  
John C. Byrd ◽  
Thomas S. Lin ◽  
James T. Dalton ◽  
Di Wu ◽  
Mitch A. Phelps ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Tumor Lysis Syndrome ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Loading Dose ◽  
Bulky Disease ◽  
Median Response

AbstractDespite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200 × 109/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases.

scholarly journals Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia

2016 ◽  
Vol 23 (9) ◽  
pp. 2154-2158 ◽  
Author(s):  
Preetesh Jain ◽  
Michael J. Keating ◽  
William G. Wierda ◽  
Mariela Sivina ◽  
Philip A. Thompson ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Long Term Follow Up
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