Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase 2 Study of an MRD-driven Approach

[AussieNeil]

Purpose: Ibrutinib has transformed the management of CLL, though its use is limited by toxicity and resistance. In this study, we utilized an “add on” approach for patients treated with ibrutinib in the front-line or R/R settings with detectable MRD. Umbralisib and ublituximab (U2) were added on to ibrutinib, patients were treated until achieving undetectable-MRD (U-MRD), and then they entered a period of treatment free observation (TFO).

From Results:

Patients received ibrutinib for a median of 21 months (range 7 - 67) prior to study enrollment. Fourteen patients (52%) have achieved U-MRD per protocol while 78% had at least one U-MRD evaluation. Seventeen patients (63%) have entered TFO after a median of 6.4 months on triplet therapy. PFS at 12 months was estimated at 95%. Grade ≥3 adverse events were hypertension 7%, diarrhea 4%, increased ALT/AST 4%.

Conclusions: This triplet approach utilizes addition of U2 to ibrutinib as an MRD-driven time-limited therapy. This therapy was well tolerated and effective. TFO following this therapy appears durable.-

aacrjournals.org/clincancer...

Clincial trial entry July 2019

clinicaltrials.gov/ct2/show...

Neil

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[hervec]

Bonjour Yes BUT "FDA investigating possible increased risk of death with lymphoma medicine Ukoniq (umbralisib)"

regards

fda.gov/drugs/development-a...

[AussieNeil Partner Administrator in reply to hervec]

Perhaps the trade off of giving umbralisib for a limited time in a protocol achieving a higher rate of uMRD, so more patients can stop treatment, will result in FDA approval? Indeed it will be interesting to see if a phase 3 trial follows.

Neil