Precision Medicine Wrap-up: Combination Therapies in CLL

Recent coverage from Targeted Oncology® highlights how combination therapies are impacting the treatment spectrum for chronic lymphocytic leukemia (CLL).

Combination therapies that target different pathways are impacting the current treatment spectrum for chronic lymphocytic leukemia (CLL).

In a Q&A with Targeted Oncology®, Philip Thompson, MB, BS, assistant professor at the University of Texas MD Anderson Cancer Center, explained that “there’s a dizzying array of studies going on” that investigate Bruton tyrosine kinase (BTK) inhibitors with other agents.

Adding a BTK inhibitor to venetoclax, for instance, increases the rate of undetectable minimal residual disease (MRD), for instance, he explained. Trials are now looking at an MRD-directed approach using BTK inhibitor combination therapies to determine if patients continue on maintenance, discontinue therapy, or continue with combination therapy.

What still isn’t known is if adding a CD20 monoclonal antibody on top of a BTK inhibitor combination therapy, such as ibrutinib plus venetoclax, provides a benefit.

“My suspicion is that a CD20 antibody is going to add very little to that combination,” Thompson said.

Read the full Q&A at Targeted Oncology®.

Data published in Blood revealed that ibrutinib plus venetoclax showed a favorable benefit-risk profile in patients with relapsed or refractory CLL. The VISION/HOVON 141 trial is an ongoing study to determine the feasibility of MRD-guided treatment cessation and reinitiation.

In the trial, a total 230 patients will receive ibrutinib until disease progression and venetoclax for 15 cycles in the first experimental arm. Patients who achieved a partial response or better were randomized 1:2 to receive either ibrutinib maintenance or observation (aka stopping therapy). The data published in Blood are a preplanned interim analysis on the first 51 eligible patients.

Of the 51 patients evaluated, 43 completed all 15 cycles of treatment. Half of the patients experienced grade 3 adverse events (AEs), and 26% experienced grade 4 AEs. Twenty-nine patients achieved complete response and 13 patients achieved a partial response. More than half (55%) reached undetectable MRD in peripheral blood at cycle 15.

Read more at Targeted Oncology®.

Finally, the FDA accepted a biologics license application (BLA) for ublituximab in combination with umbralisib to treat patients with CLL and small lymphocytic lymphoma. Ublituximab is an investigational anti-CD20 monoclonal antibody, and umbralisib is an oral phosphoinositide 3 kinase (PI3K) delta and casein kinase (CK1) epsilon inhibitor. Umbralisib (Ukoniq) is already approved in adults with relapsed or refractory marginal zone lymphoma who have received at least 1 prior anti-CD20–based regimen and in adults with relapsed or refractory follicular lymphoma who have received at least 3 prior lines of systemic therapy.

The BLA was based on the ongoing UNITY-CLL study, which has an estimated completion date of January 2024. There are 600 patients enrolled and the study is split into 4 arms:

  • Arm 1: patients receive an infusion of ublituximab on days 1, 8, and 15 followed by maintenance infusions and an oral daily dose of umbralisib
  • Arm 2: patients receive a combination of obinutuzumab and chlorambucil
  • Arm 3: patients receive ublituximab as a monotherapy
  • Arm 4: patients receive umbralisib as a monotherapy

Interim analysis data were collected from 421 patients randomized into arm 1 and arm 2. The median progression-free survival for arm 1 was 31.9 months at a median follow-up of 36.2 months compared with 17.9 months for arm 2 (HR, 0.546; 95% CI 0.413-0.720; P < .0001).

For more about the interim analysis data, visit Targeted Oncology®.

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