Ibrutinib followed by ofatumumab consolidation in previously untreated patients with chronic lymphocytic leukemia (CLL): GELLC-7 trial from the Spanish group of CLL (GELLC).

Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending. Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib. Patients received 12 cycles of ibrutinib monotherapy. Those who achieved CR after this induction were maintained on ibrutinib. Conversely, those who did not attain CR continued with ibrutinib in addition to a consolidation, which involved 7 doses of ofatumumab. The primary objective was the complete response (CR) rate at cycle 20. This study is registered within the EU Clinical Trials Register (EudraCT 2016-004937-26). Findings: Between September 8, 2017, and May 21, 2018, 84 patients (median age, 69 years) were included. After completion of 12 cycles of ibrutinib (n = 80), 4 patients (5%) were in CR, 67 (84%) in partial response (PR), and 6 patients (7%) had a PR with lymphocytosis (PRL). After consolidation with ofatumumab, 20 patients improved the response from PR to CR and 6 patients with PRL obtained a PR. Seventy-one patients (85%) completed 20 cycles of treatment, with a CR rate of 24/71 (34%). According to the intention-to-treat analysis at cycle 20, the ORR was 69/84 (82.2%), with a CRR of 24/84 (28.6%). Progression-free survival and overall survival at 48-months were 89.9% (CI: 82.4-95.5) and 92.2% (CI: 85.3-97.1), respectively. Interpretation: These findings underscore the potential for a consolidation strategy in CLL, wherein the addition of a mAb in patients with low tumor burden might enhance the quality of the response. Funding: The study was funded by Janssen that also supplied ibrutinib, whereas ofatumumab was supplied by Novartis.

Hematological, immunophenotypic, and cytogenetic characteristics of acute myeloblastic leukemia with trisomy 11.

We evaluated the incidence of trisomy 11 in acute myeloblastic leukemia (AML) and its correlation with the most relevant clinical, biological, and immunophenotypic disease characteristics in a total of 399 consecutive AML patients. Trisomy 11 was found in 15 patients (3.8%), in 3 of them as the sole abnormality. Median age was 68 years (range 48-87); 87% of patients were older than 60 years. Seven patients displayed multilineage dysplasia. Cytogenetics showed an association with trisomy 8 in six patients, and in five cases with a del(5q); nine patients had complex karyotypes. In all cases, in situ hybridization studies revealed three copies of the MLL gene, but no rearrangements or tandem duplications of MLL. Immunophenotypic analysis of blast cells showed a constant immature immunophenotypic profile with CD34 or CD117 expression (or both) in all cases analyzed. The complete remission rate was 43%; median survival time was only 2 months.