Suman Kambhampati, MD
BTK inhibitor–based regimens, chimeric antigen receptor (CAR) T-cell therapy, and venetoclax (Venclexta) combined with rituximab (Rituxan) are all novel, therapeutic strategies that recently showed efficacious outcomes in patients with chronic lymphocytic leukemia (CLL), according to Suman Kambhampati, MD.
For example, studies evaluating the BTK inhibitor ibrutinib (Imbruvica) in combination with other agents—such as obinutuzumab (Gazyva), chemoimmunotherapy regimens, venetoclax, and CD19-directed CAR T-cell therapy—all demonstrated encouraging outcomes. Specifically, the combination of ibrutinib and obinutuzumab in the frontline setting for patients with CLL or small lymphocytic lymphoma (SLL) was associated with encouraging data in the phase III iLLUMINATE (PCYC-1130) trial.
Results showed that the combination demonstrated a 77% reduction in the risk of progression or death compared with chlorambucil plus obinutuzumab.1
Moreover, at a median follow-up of 31 months, the median progression-free survival (PFS), as assessed by an independent review committee, was not reached compared with 19 months for chlorambucil and obinutuzumab (HR, 0.23; 95% CI, 0.15-0.37; P
<.0001). Based on these data, the FDA approved the ibrutinib/obinutuzumab combination in January 2019 for treatment-naïve patients with CLL/SLL.
Secondly, findings of a prospective trial demonstrated that anti-CD19 CAR T-cell therapy with CART19 showed a 43% complete response (CR) rate, 94% bone marrow remission rate, and a 78% minimal residual disease (MRD)-negative response rate in patients with CLL who did not achieve a CR following 6 months of ibrutinib treatment.2
Based on these encouraging data, the regimen will be further tested in larger trials.
Additionally, the combination of venetoclax and rituximab led to an improved PFS and high rates of undetectable MRD (uMRD) in relapsed/refractory patients.3
In an interview during the 2019 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Kambhampati, the co-director of the Blood Cancer Center at Sarah Cannon Cancer Institute, HCA Midwest Health, reflected on the emergence of data in CLL from the 2018 ASH Annual Meeting.
OncLive: One of your presentations at the State of the Science SummitTM was on CLL. Could you highlight what is new in this space?
: One of the resounding themes of the 2018 ASH Annual Meeting was the introduction of novel drugs. There were also some new themes evolving from the novel drugs, showing that compared with our traditional bones of chemoimmunotherapy, BTK inhibitors—especially ibrutinib—is a practice-changing paradigm both in the young and elderly patient populations. We saw that results were better with ibrutinib-based combinations.
We also saw some unique combinations with chemoimmunotherapy and ibrutinib presented, showing that it produces early and deep MRD-negative responses, which we hope will be translated into a bigger cooperative study group.