CLL: Therapy, excluding Transplantation: Advances in CLL Using Novel Combination Therapy

691  Ibrutinib + Obinutuzumab Versus Chlorambucil + Obinutuzumab As First-Line Treatment in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL): Results from Phase 3 iLLUMINATE

Carol Moreno, et al.

The Abstract concludes: Ibr-G resulted in superior PFS regardless of high-risk genomic features, compared with clb-G, a standard CIT regimen. Response rates and depth of remission (CR and undetectable MRD) were also higher with ibr-G. Combination therapy with ibr-G was tolerable with no new safety signals identified and represents an effective chemotherapy-free treatment option for first-line CLL/SLL including the high-risk population.


692  Acalabrutinib in Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): Updated Results from the Phase 1/2 ACE-CL-001 Study

John C. Byrd, et al.

The Abstract concludes: Acalabrutinib monotherapy produced high response rates and demonstrated an acceptable safety profile in patients with TN CLL.


693  Phase 2 Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia

Kerry A. Rogers, et al.

The Abstract concludes:OBIN, IBR, and VEN in combination have a tolerable safety profile in both RR and TN CLL patients with the majority of toxicities being hematologic. This regimen has a high mid-therapy response rate (92%) in RR patients with early MRD negative responses. EOT responses in TN and RR patients will be presented at the meeting.


694  Durable Remissions after Discontinuation of Combined Targeted Treatment in Patients with Chronic Lymphocytic Leukemia (CLL) Harbouring a High-Risk Genetic Lesion (del(17p)/TP53 Mutation)

Paula Cramer, et al.

The Abstract concludes: In patients with del(17p)/TP53 mutations, the rate of MRD negative remissions achieved with venetoclax and obinutuzumab is higher than with ibrutinib combined with either obinutuzumab or ofatumumab. Disease control seems durable in patients achieving a MRD negative remission by one of these combinations, as 13 of 17 patients show ongoing remissions after a median observation time of more than one year after termination of therapy.


695  First Prospective Data on Impact of Minimal Residual Disease on Long-Term Clinical Outcomes after Venetoclax Plus Rituximab Versus Bendamustine Plus Rituximab: Phase III MURANO Study

Arnon P. Kater, et al.

The Abstract concludes: The higher PB uMRD rate observed at EOCT in the VenR arm vs BR arm was maintained at completion of Ven treatment, including in high-risk subgroups, consistent with maintained PFS benefit seen with longer follow up. VenR pts who achieved uMRD or int-MRD+ had durable PFS. MRD status powerfully identified distinct outcomes for pts with PR/nPR; longer follow-up is needed to determine the impact of MRD status among CR/CRi. In the first yr post-completion of fixed-duration VenR treatment, majority of uMRD pts remained uMRD; reemergence of MRD+, mainly at int levels, is seen in a minority of pts, and has shown a low rate of progression to clinical PD to date. These data are the first to demonstrate the value of PB MRD as a predictive marker of clinical outcome for the fixed-duration chemotherapy-free regimen, VenR. Our data corroborate that uMRD and int-MRD+ rate is a meaningful endpoint and desirable goal of CLL therapies, including targeted agents.


696  Validation of Clinical Prognostic Models and Integration of Genetic Biomarkers of Drug Resistance in CLL Patients Treated with Ibrutinib

Inhye E. Ahn, et al.

The Abstract concludes: We developed and validated prognostic models to predict the risk of disease progression or death in CLL patients treated with ibrutinib. Risk groups classified by three commonly available pre-treatment factors showed statistically significant differences in PFS. The clinically-defined high-risk disease was linked to higher propensity to develop clonal evolution with BTK and/or PLCG2 mutations, which heralded ibrutinib resistance.