scholarly journals Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study

2015 ◽  
Vol 33 (30) ◽  
pp. 3467-3474 ◽  
Author(s):  
Laurie H. Sehn ◽  
Andre Goy ◽  
Fritz C. Offner ◽  
Giovanni Martinelli ◽  
M. Dolores Caballero ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hodgkin Lymphoma ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Indolent Lymphoma ◽  
Previous Response ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20+ indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m2). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm. Conclusion Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials.

scholarly journals NOVEL DRUGS IN FOLLICULAR LYMPHOMA

2016 ◽  
Vol 8 ◽  
pp. 2016061 ◽  
Author(s):  
Giuseppe Rossi ◽  
Antonella Anastasia
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Free Treatment ◽  
Phase Iii Trials ◽  
New Treatment ◽  
Anti Cd20 ◽  
Key Steps

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of a chieving a definite cure, have prompted investigations into the possible role of more effective and less toxic strategies with innovative therapeutic agents.  Recently Casulo et al demonstrated that approximately 20% of patients with FL actually relapse within 2 years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis.Evolving strategies for difficult to treat FL patients have recently considered  immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), with mAbs directed against other surface antigens such as CD22 and CD23 (epratuzumab, lumiliximab), with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inibithors(idelalisib, duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies,  taking into account their toxicity. Of course we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study

2013 ◽  
Vol 31 (23) ◽  
pp. 2920-2926 ◽  
Author(s):  
Gilles A. Salles ◽  
Franck Morschhauser ◽  
Philippe Solal-Céligny ◽  
Catherine Thieblemont ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Group Versus ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Non Hodgkin Lymphoma ◽  
Flat Dose ◽  
End Of Treatment ◽  
Grade 3 ◽  
Anti Cd20

Purpose The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Patients and Methods Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg). Results Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory. The overall response rate at the end of treatment was 55% (95% CI, 32% to 76%) in the 1,600/800-mg group (9% complete responders) and 17% (95% CI, 4% to 41%) in the 400/400-mg group (no complete responders). Five of 10 rituximab-refractory patients had an end-of-treatment response in the 1,600/800-mg group versus one of 12 in the 400/400-mg group. Median progression-free survival was 11.9 months in the 1,600/800-mg group (range, 1.8 to 33.9+ months) and 6.0 months in the 400/400-mg group (range, 1.0 to 33.9+ months). The most common adverse events were infusion-related reactions (IRRs) seen in 73% of patients, but only two patients had grade 3 to 4 IRRs (both in the 1,600/800-mg group). No IRRs were considered serious, and no patients withdrew for IRRs. Conclusion The 1,600/800-mg dose schedule of obinutuzumab (GA101) has encouraging activity with an acceptable safety profile in relapsed/refractory indolent non-Hodgkin lymphoma.

A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1606-1612 ◽  
Author(s):  
Oliver W. Press ◽  
Joseph M. Unger ◽  
Rita M. Braziel ◽  
David G. Maloney ◽  
Thomas P. Miller ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Oncology Group ◽  
Chop Chemotherapy ◽  
Southwest Oncology Group ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Trial ◽  
Main Adverse Event ◽  
Anti Cd20

AbstractAdvanced follicular lymphoma is incurable with conventional chemotherapy and radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase 2 trial (S9911) of a novel regimen consisting of 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed 4 to 8 weeks later by tositumomab/iodine I 131 tositumomab (anti-CD20 antibody) in 90 eligible patients with previously untreated, advanced stage follicular lymphoma. Treatment was well tolerated. Reversible myelosuppression was the main adverse event and was more severe during CHOP chemotherapy than following radioimmunotherapy. The overall response rate to the entire treatment regimen was 90%, including 67% complete remissions (CRs plus unconfirmed CRs [CRu's]) and 23% partial remissions (PRs). Twenty-seven (57%) of the 47 fully evaluable patients who achieved less than a CR with CHOP improved their remission status after tositumomab/iodine I 131 tositumomab. With a median follow-up of 2.3 years, the 2-year progression-free survival (PFS) was estimated to be 81%, with a 2-year overall survival of 97%. This study has established the feasibility, tolerability, and efficacy of this regimen for patients with advanced follicular lymphoma. This novel treatment appears promising compared with the SWOG's historical experience using CHOP alone and is currently being compared with CHOP plus rituximab in a randomized phase 3 trial (S0016).

Phase III randomized study of sorafenib plus doxorubicin versus sorafenib in patients with advanced hepatocellular carcinoma (HCC): CALGB 80802 (Alliance).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Donna Niedzwieski ◽  
Jennifer J. Knox ◽  
Andreas Kaubisch ◽  
James Posey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hepatic Failure ◽  
Randomized Study ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Secondary Malignancy ◽  
Advanced Hepatocellular Carcinoma ◽  
Prior Systemic Therapy

192 Background: An exploratory analysis of a randomized phase II study in HCC comparing doxorubicin (D) alone to doxorubicin plus sorafenib (D+S) showed a significant improvement in overall survival favoring D+S (JAMA, 2011). The results appeared promising compared to the historic outcomes seen in the pivotal sorafenib (S) trials. CALGB 80802 was designed to determine if D+S improved survival compared to S alone. Methods: Patients with histologically proven advanced HCC, no prior systemic therapy and Child-Pugh A were randomized to receive D 60 mg/m2 every 21 days plus S 400 mg PO twice daily (D+S) or S alone. For bilirubin ≥ 1.3x normal, D and S doses were halved. D was maxed out at 360 mg/m2. The study was stratified by extent of disease (locally advanced; metastatic), the primary endpoint was overall survival (OS); and secondary endpoint progression-free survival (PFS). The final analysis was to occur when 364 events were observed among 480 total patients, with 90% power to detect a 37% increase in median OS (10.7 to 14.7 months; 1-sided α = 0.05). Results: The Alliance DSMB halted the study after accrual of 346 patients (173 on each of D+S and S) when a futility boundary was crossed at a planned interim analysis. With 107 events in each arm, median OS was 9.3 months (95%CI 7.1-12.9) for D+S, and 10.5 months (95% CI 7.4-14.3) for S with a hazard ratio (HR) 1.06 (95% CI 0.8-1.4) for D+S vs. S. Median PFS was 3.6 (95% CI 2.8-4.6) and 3.2 months (95% CI 2.3-4.1), respectively (HR = 0.90, 95% CI 0.72-1.2). There were 38 deaths on treatment: 18 on D+S and 20 on S. Among these 8 [sepsis (1), dysphagia (1), pneumonia (1), cardiac (2), hepatic failure (2), and not otherwise specified (1)] on D+S, and 3 [fatigue (1), hepatic failure (1), and a secondary malignancy (1)] on S, were at least possibly related to treatment. A maximum grade 3 or 4 only hematologic adverse events (AE) occurred in 37.8% of patients on D+S and 8.1% of patients on S. Non-hematologic AEs were comparable, in 63.6% and 61.5% of patients, respectively. Conclusions: The addition of D to S resulted in higher toxicity and did not improve OS or PFS. The S median OS of about 10 months is consistent with previous reports. NCI Grant U10CA180821 Clinical trial information: NCT01015833.

scholarly journals Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study

2009 ◽  
Vol 27 (10) ◽  
pp. 1607-1614 ◽  
Author(s):  
Howard Hochster ◽  
Edie Weller ◽  
Randy D. Gascoyne ◽  
Thomas M. Habermann ◽  
Leo I. Gordon ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Residual Disease ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Phase Iii ◽  
Indolent Lymphoma ◽  
Free Survival ◽  
Rank One

Purpose To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma. Patients and Methods Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m2 once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point. Results Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 × 10−10 [all patients]) and 64% MR v 33% OBS (HR = 0.4; P = 9.2 × 10−8 [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03). Conclusion The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS.

Phase II Study of Ofatumumab in Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report from the German Hodgkin Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2729-2729
Author(s):  
Dennis A. Eichenauer ◽  
Helen Goergen ◽  
Annette Pluetschow ◽  
Karolin Behringer ◽  
Stefanie Kreissl ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Antibody Treatment ◽  
Non Hodgkin Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for approximately 5% of all Hodgkin lymphoma (HL) cases. One hallmark of NLPHL is the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. To shed more light on the role of anti-CD20 antibody treatment in relapsed NLPHL, we conducted a phase II study evaluating the fully humanized anti-CD20 antibody ofatumumab in 28 patients. Treatment consisted of 8 weekly doses (week 1: 300 mg, week 2-8: 1000 mg) of the antibody. Results: The median age of study patients was 45 years (range: 22-68) and the majority were male (64%). A median of 1 line of therapy (range: 1-5) had been applied prior to study treatment and 7/28 patients (25%) already had rituximab-containing treatment. At the final restaging 3 months after the end of treatment, response was documented in 27/28 patients (96%; 95%-CI: 84%-100%). After a median follow-up of 26 months, 1-year and 2-year progression-free survival (PFS) estimates were 93% and 80%, respectively. No patient died. Transformation into aggressive non-Hodgkin lymphoma (NHL) occurred in 2/28 patients (7.1%). No grade III/IV toxic events were observed. Conclusion: In summary, the anti-CD20 antibody ofatumumab represents a highly active and well tolerated treatment option in relapsed NLPHL. Longer follow-up is required for final conclusions. Disclosures Off Label Use: Ofatumumab in lymphocyte-predominant Hodgkin lymphoma. von Tresckow:Takeda: Consultancy; Celgene: Other: honoraria for preparation of scientific educational events; Novartis: Consultancy, Other: Travel and accomodation, Research Funding; Amgen: Other: honoraria for preparation of scientific educational events. Borchmann:Millennium: Research Funding. Engert:Takeda: Consultancy, Research Funding.

Chimeric Anti-CD20 Monoclonal Antibody (Rituximab;Mabthera) in Remission Induction and Maintenance Treatment of Relapsed /Resistant Follicular Non-Hodgkin’s Lymphoma: Final Analysis of a Phase III Randomized Intergroup Clinical Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 353-353 ◽  
Author(s):  
Marinus H.J. Van Oers ◽  
Martine Van Glabbeke ◽  
Ivana Teodorovic ◽  
Cynthia Rozewicz ◽  
Richard Klasa ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Remission Induction ◽  
Induction Treatment ◽  
Rituximab Maintenance ◽  
Study Results

Abstract Background. Last year we reported interim results of a randomised phase III trial in patients with relapsed/refractory stage III/IV positive follicular NHL, demonstrating that the addition of rituximab (R) to CHOP chemotherapy for remission induction as well as rituximab maintenance treatment significantly improves the clinical outcome (Blood2004;104:169a). Based on these interim results, randomisation to the induction part of the trial was halted and the protocol was amended. Study design. Patients with stages III or IV follicular lymphoma at initial diagnosis and relapsed after or resistant to a maximum of two non-anthracycline containing systemic chemotherapy regimens, were randomized to remission induction with either 6 cycles of standard CHOP (once every 3 weeks) or CHOP + R (375 mg /m2 at day 1 of each cycle of CHOP). Those with a complete or partial remission after 6 cycles of therapy underwent a second randomization to no further treatment (observation) or maintenance treatment with R (375 mg/m2 once every 3 months) until relapse or for a maximum period of two years. Results. At the time of the preplanned second interim analysis (February 2004) 461 patients had been included. Of these, 369 could be evaluated for response (188 CHOP; 181 R-CHOP). Both treatment arms yielded similar partial response rates (CHOP: 53.7% - R-CHOP: 52.5%), but highly significant different CR rates (CHOP: 18.1%; R-CHOP: 30.4%; p=0.0004). Of 319 patients randomized for maintenance treatment, 268 were evaluable (132 observation; 136 R maintenance). A highly significant advantage was observed in progression free survival in patients randomized to R maintenance, when compared with the observation arm (median PFS 38 vs.15 months; p<0.0001). At that time there was no impact on OS: the observed difference (in favor of R maintenance) was not significant for an interim analysis. Toxicity of CHOP and R-CHOP induction was similar, and R maintenance was associated with minimal toxicity. These results of the planned second interim analysis showed that the formal criteria for stopping the trial had been met. It was concluded that this is the first trial to show that: 1) in patients with relapsed/resistant follicular lymphoma R-CHOP remission induction results in a highly significant increase in CR rate as compared to CHOP; 2) rituximab maintenance treatment significantly improves PFS in patients responding to induction treatment. The final analysis of the study results will be performed in September 2005, with an additional follow-up of at least 18 months. The final results will be presented at the meeting.

scholarly journals Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study

2018 ◽  
Vol 36 (22) ◽  
pp. 2259-2266 ◽  
Author(s):  
Bruce D. Cheson ◽  
Neil Chua ◽  
Jiri Mayer ◽  
Greg Dueck ◽  
Marek Trněný ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Intention To Treat ◽  
Non Hodgkin Lymphoma ◽  
Grade 3 ◽  
Overall Survival Benefit

Purpose To perform an updated analysis of the randomized phase III GADOLIN trial in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated with obinutuzumab (GA101; G) and bendamustine (B). Patients and Methods Patients with histologically documented, rituximab-refractory CD20+ indolent non-Hodgkin lymphoma received G 1,000 mg (days 1, 8, and 15, cycle 1; day 1, cycles 2 to 6) plus B 90 mg/m2/d (days 1 and 2, all cycles) or B 120 mg/m2/d monotherapy. Patients who did not experience disease progression with G-B received G maintenance (1,000 mg every 2 months) for up to 2 years. The primary end point was progression-free survival (PFS). Results Of 413 randomly assigned patients (intention-to-treat [ITT]: G-B, n = 204; B monotherapy, n = 209), 335 had follicular lymphoma (FL; G-B, n = 164; B monotherapy, n = 171). After a median follow-up of 31.8 months, median PFS in ITT patients was 25.8 months (G-B) and 14.1 months (B monotherapy; hazard ratio [HR], 0.57; 95% CI, 0.44 to 0.73; P < .001). Overall survival (OS) also was prolonged (HR, 0.67; 95% CI, 0.47 to 0.96; P = .027). PFS and OS benefits were similar in patients with FL. Grade 3 to 5 adverse events (AEs) were reported by 148 (72.5%) and 133 (65.5%) patients in the G-B and B monotherapy arms, respectively, most commonly neutropenia (G-B, 34.8%; B monotherapy, 27.1%), thrombocytopenia (10.8% and 15.8%), anemia (7.4% and 10.8%), and infusion-related reactions (9.3% and 3.4%). Serious AEs occurred in 89 G-B patients (43.6%) and 75 B monotherapy patients (36.9%); fatal AEs occurred in 16 (7.8%) and 13 (6.4%), respectively. Conclusion This updated analysis confirms the PFS benefit for G-B shown in the primary analysis. A substantial OS benefit also was demonstrated in the ITT population and in patients with FL. Toxicity was similar for both treatments.

Comparison of Cladribine Plus Cyclophosphamide With Fludarabine Plus Cyclophosphamide As First-Line Therapy for Chronic Lymphocytic Leukemia: A Phase III Randomized Study by the Polish Adult Leukemia Group (PALG-CLL3 Study)

2010 ◽  
Vol 28 (11) ◽  
pp. 1863-1869 ◽  
Author(s):  
Tadeusz Robak ◽  
Krzysztof Jamroziak ◽  
Joanna Gora-Tybor ◽  
Beata Stella-Holowiecka ◽  
Lech Konopka ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Deletion ◽  
Randomized Study ◽  
Nucleoside Analogs ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Tp53 Gene ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
First Line

Purpose Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. Patients and Methods Patients received cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (CC regimen) or fludarabine at 25 mg/m2 combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (FC regimen), every 28 days for up to six cycles. The primary end point was complete response (CR) rate. Secondary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. Results Of 423 randomly assigned patients (211 to CC and 212 to FC), 395 were evaluated in the final analysis. The CR and ORR reached 47% and 88% in the CC arm and 46% and 82% in the FC arm (P = .25 and P = .11, respectively). The median PFS was 2.34 years with CC and 2.27 years with FC (P = .51). OS and grade 3/4 treatment-related toxicity were also comparable. Moreover, we did not observe any significant differences in CC and FC efficacy across different patient prognostic subgroups that included patients with 17p13 (TP53 gene) deletion who had poor survival in both study arms. Conclusion Cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive CLL. Both combinations have unsatisfactory activity in patients with 17p13 (TP53 gene) deletion.

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