CLL – Clinical Poster Session: Friday, June 10

Conference Correspondent - EHA 2016

Integrated safety analysis of venetoclax monotherapy in CLL

Venetoclax is an oral BCL-2 inhibitor with activity in patients with relapsed and refractory chronic lymphocytic leukemia (CLL). Based on an integrated safety analysis and using tumor lysis syndrome (TLS) mitigation guidelines, 4 (4%) of 105 patients experienced laboratory TLS, all grade 3. These events were observed within the initial 5 weeks and were managed with hydration, electrolyte correction, and dose interruption. All patients resumed venetoclax without clinical sequelae.

Impact of adding rituximab to venetoclax on the rate, quality, and duration of response in patients with relapsed/refractory CLL: a cross-study multivariable analysis

The combination of venetoclax and rituximab, given monthly for 6 months, is being evaluated in an ongoing phase 1b study. To date, the overall response rate (ORR) is 86% (47% complete response [CR]). Using post hoc exploratory multivariable analyses, researchers assessed the effect of adding rituximab to venetoclax on ORR, quality of response, and duration of response (DoR) relative to venetoclax monotherapy. Venetoclax plus rituximab results in higher CR rates and longer DoR (vs venetoclax alone) after adjusting for patient demographics and disease characteristics. An ongoing phase 3 study (MURANO) randomizes venetoclax plus rituximab with bendamustine plus rituximab in relapsed CLL.

Real-world experience of ibrutinib in >2900 CLL patients: data from a global named patient program (NPP)

More than 2900 patients with CLL are participating in a global NPP that allows access to ibrutinib prior to approval. After 12 months, 77% of this population remained on ibrutinib, a rate that is similar to the 12-month time on treatment (82%) and progression-free survival (84%) rates observed in the phase 3 RESONATE study of ibrutinib in relapsed and refractory CLL. In total, 11% of patients discontinued ibrutinib during the observation period, most commonly because of death (4%), disease progression (2%), and adverse events (2%).This analysis of real-world data suggests that results observed in ibrutinib clinical trials are reproducible in clinical practice.

Improvement in quality of life (QOL) and well-being in older patients with treatment-naïve CLL: results from the randomized phase 3 study of ibrutinib versus chlorambucil (RESONATE-2)

Because CLL primarily affects older patients with comorbidities and disease-related immunosuppression, improvement of health-related QOL is an important clinical end point. A recent phase 3 trial (RESONATE-2) showed superior progression-free survival, overall survival, and overall response rate for ibrutinib compared with chlorambucil in older treatment-naïve patients with CLL. Here, researchers report that ibrutinib is associated with greater improvements in QOL and hematologic function, as well as reduction in disease burden. The drug’s safety profile is also favorable: 87% of elderly patients with comorbidities continued ibrutinib after a median of 1.5 years of follow-up.

Long-term follow-up of the next generation PI3K-delta (δ) inhibitor TGR-1202 demonstrates safety and high response rates in CLL: integrated-analysis of TGR-1202 monotherapy and combined with ublituximab (UTX)

TGR-1202 is a novel, once-daily PI3Kδ inhibitor with activity in advanced hematologic malignancies. It is currently in clinical development as monotherapy and in combination with the glycoengineered CD20 monoclonal antibody, UTX. An integrated analysis of patients with CLL and small lymphocytic lymphoma who were dosed with TGR-1202 as monotherapy or combined with UTX demonstrates that TGR-1202 has a markedly different safety profile from other PI3Kδ inhibitors. There were few discontinuations per toxicity and limited grade 3/4 events. Robust activity has led to a global phase 3 trial of TGR-1202 plus UTX in treatment-naïve and relapsed CLL. TGR-1202 is also being evaluated in CLL patients intolerant to a BTK or PI3Kδ inhibitor.