ASH: AbbVie, Roche's fixed-duration Venclexta combos gain steam in CLL

Venclexta
AbbVie and its partners are trialing Venclexta in tandem with Imbruvica in previously untreated CLL patients. (AbbVie)

Johnson & Johnson and AbbVie’s Imbruvica is the standard of care in previously untreated chronic lymphocytic leukemia (CLL). But patients have to take it indefinitely, which can be difficult, both mentally and physically.

Enter AbbVie and Roche’s Venclexta, which the drugmakers are working to show can combine with Imbruvica to offer effective therapy for patients who take a fixed duration of treatment. They padded their case Saturday at the American Society of Hematology (ASH) virtual annual meeting, showing the pairing had kept 95% of patients in a phase 2 study disease-free and alive at the one-year post-treatment mark.

Patients who received Imbruvica and Venclexta in the phase 2 Captivate study showed undetectable levels of minimal residual disease (MRD)—a commonly used metric in CLL that measures the number of leukemia cells remaining in the body after treatment—before being randomized to stop their therapy.

The cohort “had to remain free from MRD relapse as well as be progression-free, so this really speaks to the depth of the remissions that are being achieved in this patient group,” said Jim Dean, senior medical director for oncology development at AbbVie’s Pharmacyclics.

RELATED: ASH: AbbVie, Roche pad their case for fixed-duration Venclexta use in CLL

While that 95% figure was “comparable” to what researchers observed in patients who continued on solo Imbruvica, J&J’s Janssen said in a release, the combo didn't top the 100% disease-free rate the powerhouse pill posted as an indefinite therapy.

But there are other benefits to fixed-duration treatment that may give the combo the advantage for some patients. “I think that time off treatment is really important,” Dean said, adding, "The fixed duration can give them the comfort to know they have to get through a fixed period of treatment and then they’ll get a break from that."

These “treatment holidays” are particularly important for younger or more active patients, who “don’t want to be tied down to having to take a pill all the time." They're also key for those who suffer from Imbruvica side effects, who can say, "'I just need to get to this point in time and then I’ll have a chance for that side effect to go away,’” Dean added.

Looking ahead, the tandem therapy will have to replicate its performance in phase 3 before heading off to regulators for approval. But in the meantime, Venclexta continues to add evidence supporting fixed-duration therapy elsewhere in CLL treatment.

RELATED: AbbVie, Roche drive Venclexta toward $3B with Rituxan combo nod in CLL

Also at ASH, AbbVie and Roche unveiled five-year results showing that a chemo-free marriage of Venclexta and Roche’s Rituxan helped previously treated patients go a median of 53.6 months without seeing their disease worsen, compared with 17 months for a combination of Rituxan and the chemo drug bendustamine.

The data build on last year’s ASH performance, which showed Venclexta and Rituxan had reduced the risk of disease progression or death by 81% at the four-year mark.

“Prior to these results, it was less certain whether those deep remissions would convincingly translate to really durable remissions and long progression-free survivals. That was an unanswered question,” John Hayslip, M.D., executive medical director at AbbVie, said of the five-year showing, which comes from the phase 3 Murano trial. “Now, we see with five years of follow-up that fixed duration administration indeed is not just high remission rates, but durable and long-lasting.”