Year: 2019
Type: article
Abstract: Days 1 and 2 of subsequent cycles.The primary endpoint was ORR; secondary endpoints: best response rate, OS and PFS, response duration (RD) and minimal residual disease (MRD) rate (flow cytometry; sensitivity: 1 CLL cell in 10 -4 leucocytes).We present the results of an interim analysis at 17 months of last Obi-B cycle with the data cut-off date of 22nd March 2018.Results: Pts were mostly male (66.7%), with a median age of 67.9 years and ECOG 0 in 62.5% of them.RAI clinical stage was 0-II in 52.7% pts and III-IV in 47.3% pts.Expression of CD38 (>30%), CD49D (>20%), ZAP-70 (>20%) was seen in 15.3%, 55.6%, and 39.4% of pts respectively, and IGHV unmutated in 75.0% of pts.Genetic abnormalities detected were: del13q(43.1%),trisomy 12(19.4%),del11q/ATMmutation(43.1%),del17p/p53mutation (26.4%), mutations of BIRC3(2.8%),SF3B1(8.3%) and NOTCH1 (20.8%).Out of 72 enrolled pts, 80.6% and 79.2% completed 6 cycles of treatment with Obi and B respectively.Median treatment duration was 4.9 months and discontinuation rates due to adverse events were 16.7% (Obi) and 18.1% (B).Obi and B doses were modified in 75% and 54.2% of pts, respectively.ORR was 76.4 % (CR 27.8%, CRi 8.3% and PR 40.3%),PD (4.2%) and SD (8.3%).After a median follow-up of 23.6 months, median RD and PFS (Fig 1.) were 8.1 and 24.1 months, respectively and median OS was not reached.PFS and OS (Fig. 1) were significantly higher (p<0.001) in pts with negative MRD, mutated IGHV and no p53 aberrations in peripheral blood.Median time to re-treatment was 33.9 months.64 pts (88.9%) presented at least 1 toxicity, being the most common grade 3/4 neutropenia (52.8%) and thrombocytopenia (20.9%).Two deaths occurred due to toxicities (acute myeloid leukemia and septic shock).Conclusions: This preliminary analysis anticipates that the combination of obinutuzumab with bendamustine is feasible, effective and well-tolerated in relapsed/refractory CLL.Achievement of MRD negativity in peripheral blood correlates with a longer PFS and OS regardless of clinical response and cytogenetic abnormalities.
Source: Hematological Oncology
DOI: 10.1002/hon.51_2631
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2951475672