642. CLL: Therapy, excluding Transplantation: Targeting MRD Negative CLL Through Combinations of Novel Agents and Antibody


Randomized Trial of Ibrutinib Versus Ibrutinib Plus Rituximab (Ib+R) in Patients with Chronic Lymphocytic Leukemia (CLL)

Jan A. Burger, et al.

The authors of the study conclude:

The addition of rituximab to ibrutinib in relapsed and high-risk CLL patients did not improve the PFS. However, patients treated with Ib+R reached their remissions significantly faster and achieved lower MRD levels. Given these results, single-agent ibrutinib should remain standard-of-care therapy in CLL, but the addition of rituximab can be considered in patients in whom a faster response is desirable.



Initial Results of Ibrutinib Plus Venetoclax in Relapsed, Refractory CLL (Bloodwise TAP CLARITY Study): High Rates of Overall Response, Complete Remission and MRD Eradication after 6 Months of Combination Therapy

Peter Hillmen, et al.

The authors of the study conclude:

The combination of IBR with VEN is well tolerated in relapsed, refractory CLL with only two of 41 patients experiencing biochemical TLS to date. All 25 patients reaching the initial response assessment after 6 months of IBR+VEN have responded, 60% are in CR & 28% have achieved an MRD negative remission in the marrow. These early results suggest a potent synergy between ibrutinib & venetoclax.



Combined Venetoclax and Ibrutinib for Patients with Previously Untreated High-Risk CLL, and Relapsed/Refractory CLL: A Phase II Trial

Nitin Jain, et al.

The authors of the study conclude:

The combination of IBR and VEN is safe and active in pts with CLL. These early results of efficacy are highly encouraging. Significant improvement in bone marrow CLL infiltrate is noted with several pts achieving undetectable MRD status as early as 3 months of the combination therapy.



Safety, Efficacy and MRD Negativity of a Combination of Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia –  Results from a Phase 1b Study (GP28331)

Ian W. Flinn, et al.

The authors of the study conclude:

These data from the Phase 1b GP28331 study of VEN + G in 1L CLL pts show a high level of deep and durable responses with unprecedented MRD negativity rates compared with chemo-immunotherapy regimens and other novel chemo-free therapies in 1L studies. VEN + G is well tolerated and may be administered with a favorable benefit/risk profile; no clinical TLS or high-grade IRR were reported. MRD negativity, a measure of disease burden, has been shown to independently predict clinical outcomes of pts receiving combination chemo-immunotherapy; as such, the high rate of MRD negativity achieved in pts receiving VEN + G (including del(17p) pts) suggests that this combination may represent a potentially important treatment option for 1L CLL pts. VEN + G is now being tested in a phase 3 trial.



Initial Results of the Phase 2 Treatment Naive Cohort in a Phase 1b/2 Study of Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia

Kerry A. Rogers, et al.

The authors of the study conclude:

OBIN, IBR, and VEN can be given safely without TLS and appears highly effective as initial therapy for CLL after response assessment at this initial (C8) time point. Objective responses, including MRD-negative complete responses, have been achieved in all patients to date and results for the primary endpoint of MRD (-) CR after C14 are expected in May 2018. Updated toxicity and response data will be presented for the 22 of 25 patients who remain on study.



Acalabrutinib with Obinutuzumab in Relapsed/Refractory and Treatment-Naive Patients with Chronic Lymphocytic Leukemia: The Phase 1b/2 ACE-CL-003 Study

Jennifer A. Woyach, et al.

The authors of the study conclude:

Treatment with acalabrutinib plus obinutuzumab was well-tolerated and yielded high response rates that deepened over time in both R/R and TN patients. Most patients (41/45 [91%]) remain on treatment with a median follow-up of 21 months.