PB1901 IBRUTINIB, SINGLE AGENT BTK INHIBITOR, FOR RELAPSED/REFRACTORY (R/R) CHRONIC LYMPHOCYTIC LEUKEMIA: A REAL‐WORLD EXPERIENCE FROM RETE EMATOLOGICA PUGLIESE (REP).
Authors: Scalzulli P.R. , Guarini A. , Loseto G. , Specchia G. , Giordano A.M. , Pastore D. , Quintana G. , Maggi A. , Mazza P. , Di Renzo N. , De Paolis M.R. , Tarantini G. , De Santis G. , Pavone V. , Greco A. , Valvano M.R. , Rossi G. , Cascavilla N. 
Published: June 2019

Background:Ibrutinib has showed to improve Progression Free Survival (PFS) and Overall Survival (OS) in patients with Chronic Lymphocytic Leukemia (CLL) maintaining a good tolerability profile. Moreover a good tolerability profile was showed in previously published data.Aims:Within the Rete Ematologica Pugliese (REP) seven hematologic centers verified the safety and the efficacy of Ibrutinib as a single agent treatment. Response rate, PFS and OS have been evaluated in all treated patients and in poor cytogenetic risk groups.Methods:One hundred twenty‐two patients from seven hematologic centers of REP were enrolled in the study. Ibrutinib was administred as salvage therapy across different lines as reported: 2nd line n = 75 (61%) (BR n = 48, FCR n = 24, other n = 3); 3rd line n = 35 (28,7%); 4th line n = 12 (8,2%). All patients received Ibrutinib 420 mg once daily until progression or unacceptable toxicity. PFS, OS and Overall Response Rate (ORR) were calculated. Kaplan Meier method was used to estimate PFS/OS and differences in survival times between groups were assessed with a log‐rank test.Results:Patients have a median age of 65 years (range: 28‐84), 50% of them had more than 65 yrs. Cytogenetic FISH was performed in 66% of patients (n = 80). No abnormalities were found in 31% of patients (n = 25): while del17p, del13q, del11q and trisomy12 were found in n = 33, n = 13, n = 3 and n = 6 of patients, respectively. Unmutated and mutated IgVH status was performed in 73 patients (60%); of these, 46(63%) patients had unmutated and 27 (37%) had mutated IgVH.Overall, ORR was achieved in 94 patients (77%) (complete response [CR] was reached in 10%) of patients). In the subgroup having a del17p ORR was achieved in 21 (61%) patients. Median of follow up time is 17 months (range 1‐45). The estimated PFS at 30 months was 66,7% from the entire study population. Patients with del17p displayed a median PFS of 39 months while it was not reached in patients having no history of cytogenetic abnormalities (Figure 2). Median OS was not reached from all treated patients and the estimated OS at 30 months was 72.7%, while no difference in terms of OS was found when patients with and without del17p were compared (81.7% vs 90.2%), (overall logrank p = 0.807) (Figure 4).Out of all treated patients, 47% of them showed the following adverse events (AEs) with grade ≥3: neutropenia (16%), hypertension (12%), atrial fibrillation (3%), anemia (3%), diarrhea (2%).Summary/Conclusion:In REP real‐world experience, treatment for R/R CLL patients with Ibrutinib as a single agent demonstred to be effective across negative and positive cytogenetic groups and to be well tolerated. AES did not result in treatment interruptions in the most of cases. In fact, over a median follow up of 17 months, 80% of patients remain on Ibrutinib‐treatment. Clearly, these results will require longer follow up time to be further confirmed.image