Venetoclax Plus Lenalidomide Safe, Effective in Relapsed/Refractory MCL

The combination of venetoclax (Venclexta) and lenalidomide (Revlimid) was shown to be tolerable and efficacious in patients with relapsed or refractory mantle cell lymphoma in a phase Ib/II study presented at the 2022 American Society of Hematology (ASH) annual meeting.

In this exclusive MedPage Today video, Catherine S. Diefenbach, MD, of NYU Langone Health in New York City, discusses the results of the VALERIA study.

Following is a transcript of her remarks:

So these were patients with relapsed/refractory mantle cell lymphoma who failed at BTK [Bruton’s tyrosine kinase]. They were second or later line. And they treated 60 patients, and they had an overall response of 62%, with a 40% response in the BTK-pretreated patients. And of the 62%, they had quite a lot of CRs [complete responses], including in the patients who had previously been exposed to a BTK inhibitor.

There were 20 patients who stopped treatment early due to PD [progressive disease]. So these, I assume, were the PR [partial response] patients, and then a couple for AEs [adverse events], but they have 49% of the patients still in remission at 24 months. It’s clearly active. They did have one patient who had PML [progressive multifocal leukoencephalopathy], so that’s a rare complication.

But I think in summary this regimen, which is 15 mg of lenalidomide with 600 [mg] of venetoclax, is tolerable. Although neutropenia did require G-CSF [granulocyte colony-stimulating factor] support, and there was some exploration of an MRD [minimal residual disease]-driven response, so the treatment could be discontinued and then re-initiated upon MRD positivity, and this was feasible. And so this regimen certainly looked like it’s active and effective for patients with BTK-resistant mantle cell lymphoma.

Hematologic toxicity is pretty standard with both lenalidomide and venetoclax. So the fact that [there was] the grade 3-4 neutropenia doesn’t surprise me, but does mandate G-CSF. There were a lot of patients who had grade 3-4 thrombocytopenia, and eight grade 3-4 infections is not a huge number, but it’s not a tiny number. So you would want to be careful to use this therapy in patients who had pretty robust blood counts to begin with. I wouldn’t give this to a patient who had borderline counts, and someone who was pretty robust rather than someone who was frail.

So this would probably be up there and sort of higher in intensity than the R2 regimen [lenalidomide and rituximab (Rituxan)], and the venetoclax is probably adding both efficacy and also toxicity. So you really have to balance the additional benefit from the venetoclax with the additional primarily hematologic toxicity with venetoclax.