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ASCO 2020 Top 12” #8: Effect of adding ublituximab to ibrutinib on PFS, ORR, and MRD negativity in previously treated high-risk chronic lymphocytic leukemia: Final results of the GENUINE phase III study

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In short videos with accompanying text, Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, takes us through his “Top 12” abstracts from ASCO or the American Society of Clinical Oncology Annual Meeting held virtually in May, 2020.

#8

ASCO 2020: Effect of adding ublituximab to ibrutinib on PFS, ORR, and MRD negativity in previously treated high-risk chronic lymphocytic leukemia: Final results of the GENUINE phase III study

We know that ibrutinib works well for all CLL patients, but for those with high-risk features, such as del17p or TP53 aberrations, the responses tend to be less durable. Is there something more we can do to help improve outcomes?

At ASCO 2020 the final results of the GENUINE trial were reported 3 ½ years out after adding to ibrutinib, the monoclonal antibody (MAB), ublituximab (UTX).  UTX is directed against CD20, a surface marker found on B-lymphocytes, both normal and cancerous, including CLL cells. UTX was specifically engineered to increase its ability to kill its target cells.

To qualify for the trial, patients had to have relapsed or refractory CLL with high-risk features, such as del17p, del11q, and/or a TP53 mutation.

We now know that while del11q was bad news in the pre-ibrutinib era, recent data have demonstrated that patients with it do very well on ibrutinib.

Takeaways:

  • 117 patients were treated, split evenly between the 2 cohorts, ibrutinib with or without UTX.
  • Results
    • Adverse events were comparable between the arms with 2 exceptions:
      • While there were no infusions to react to in the ibrutinib arm, infusion reactions occurred in more than half of those who received UTX. Only 3% of the reactions were severe.
      • Low neutrophil counts were observed in 36% on the combo vs. 21% taking ibrutinib alone.
    • Efficacy
      • The combo was superior across all measured outcomes, though the results for those with del11q were similar in both groups.
      • Overall response rate (ORR) for the combo was 90% vs. 69% for ibrutinib alone.
      • 46% of the combo patients reached undetectable minimal or measurable residual disease (uMRD) compared to only 7% on single agent ibrutinib.
      • Progression free survival (PFS) and overall survival (OS) were also significantly better for the combo.

Conclusions:

We know that ibrutinib set the bar high. We know from the game changing large phase III Alliance A041202 collaborative multi-center trial that adding another anti-CD20 MAB, rituximab, to ibrutinib did not improve outcomes over ibrutinib alone.

So, it is a pleasant surprise to see how this newer antibody adds clinically significant punch to what ibrutinib can do on its own.

How UTX ultimately fits into future treatment paradigms is a work in progress. It does certainly seem to help high-risk patients. The obvious question is, does adding UTX to ibrutinib help more than adding obinutuzumab to ibrutinib?  There may never be a head to head trial to compare the two, but right now I am happy to see another option that ups our game, and I look forward to the approval of ublituximab to treat CLL.

Here is the ASCO 2020 abstract: Effect of adding ublituximab to ibrutinib on PFS, ORR, and MRD negativity in previously treated high-risk chronic lymphocytic leukemia: Final results of the GENUINE phase III study.

Worth a read.

Stay strong.  We are all in this together.

Brian

Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.