Christopher J. Melani, MD, discusses the results of a trial investigating a combination regimen in a cohort of patients with mantle cell lymphoma.
Christopher J. Melani, MD, assistant research physician in the Lymphoid Malignancies Branch at the Center for Cancer Research, National Cancer Institute, discusses the results of a trial investigating a combination regimen in a cohort of patients with mantle cell lymphoma (MCL).
In a phase 1b/2 clinical trial (NCT03223610), the combination of venetoclax (Venclexta), ibrutinib (Imbruvica), prednisone, obinutuzumab (Gazyva), and lenalidomide (Revlimid), or ViPOR, was assessed for safety and efficacy outcomes in several disease types, including MCL. Melani says that this regimen showed very low toxicity compared with cytotoxic chemotherapy in the cohort of 13 patients with MCL as well as other cohorts.
In addition, it showed high efficacy as all 11 patients who completed therapy had a radiographic and biopsy-assessed complete remission. All of these patients were minimal residual disease (MRD) negative after treatment.
Melani notes that this is a fixed-duration therapy with no maintenance regimen, unlike some other effective therapies in this setting, so it is not yet clear if these remissions will be durable and potentially curative. Further reporting from this trial will provide longer follow-up on these patients, the phase 2 portion of the trial will explore these results further in patients with B-cell lymphoma, including a cohort of patients with MCL.
0:08 | The first thing that was very remarkable was the lack of a significant toxicity and how well tolerated it was. And as expected, it was very effective. So far, in the patients who have been treated, there's 13 patients on study, 11 of them completed therapy, and in the patients who have finished therapy, all 11 achieved a complete remission by a negative PET scan and negative end-of-treatment bone marrow biopsy. Out of those patients, we also did do MRD analyses using circulating tumor DNA. We collaborated with Adaptive Biotechnologies using their ClonoSEQ VDJ sequencing platform, and actually found that 100% of patients were MRD negative at the end of therapy, indicating that this is a rather deep remission.
0:58 | The question at this point in time is now going to be how durable are those remissions because, with our study, compared [with] a number of the other doublet and triplet studies, we give this as a fixed-duration time-limited therapy similar to chemotherapy. [Dosing is] 6 cycles every 3 weeks, so 18 weeks or a little over 4 months with no maintenance. Other regimens often give maintenance of a year or 2 or even 3 or an indefinite therapy. It's going to be very important now with the follow-up to determine if these remissions are very durable or not, and whether we're potentially curing anyone or not. But again, it's too soon to know at this time; the follow-up for this cohort of the study is still too short.