Early Trial Shows Promising Results for Venetoclax Combination in Newly Diagnosed Mantle Cell Lymphoma

Adding venetoclax to rituximab and lenalidomide appeared to be safe and resulted in high rates of overall response and measurable residual disease (MRD) undetectability in patients with newly diagnosed mantle cell lymphoma (MCL), according to the results from a phase Ib study presented at the 2021 American Society of Clinical Oncology Annual Meeting.

“This study was designed to add to the growing body of evidence evaluating non-cytotoxic agents in patients with newly diagnosed MCL,” study presenter Tycel Jovelle Phillips, MD, from the University of Michigan Medical School, told ASH Clinical News.

The study enrolled 28 patients with previously untreated MCL and included all symptomatic patients irrespective of morphology, Ki-67, cytogenetics, p53 status, or disease stage. During the 12-month induction phase, patients received lenalidomide daily on days one to 21, rituximab weekly during cycle one and on day one of every even-numbered cycle, and venetoclax escalated to 400 mg over four weeks beginning on day eight. In the maintenance phase, rituximab was given every eight weeks for 36 months, lenalidomide for 24 months (10 mg or half of the last dose during induction), and venetoclax for a minimum of 12 months.

All patients were able to escalate therapy to venetoclax 400 mg without experiencing any dose-limiting toxicities, the authors reported.

The overall response rate was 96% (n=27/28), with a complete response rate of 89%. Of those patients who responded, two eventually experienced progressive disease. All patients who progressed had baseline TP53 mutation and none obtained MRD negativity at a level less than 10-4. Overall, 23 of 28 patients were still receiving treatment on study at the time of presentation.

MRD testing was successful in all patients, with 71% showing MRD negativity. According to Dr. Phillips, with the current follow-up there have been no relapses in patients who obtained undetectable MRD status in the peripheral blood.

“These results, while early and in a small patient population, compare favorably to what is currently used in standard practice for patients irrespective of eligibility for autologous stem cell transplantation,” Dr. Phillips said. “Given that we obtained responses in 27 of the 28 patients enrolled on the study, the overall response rate compares favorably to bendamustine-rituximab or cytarabine-based regimens.”

Dr. Phillips noted that the more important marker of this treatment would be the progression-free survival (PFS) data, which are still immature. “We would hope that obtaining high rates of MRD undetectability would translate into prolonged PFS in these patients, given the growing evidence supporting the importance of obtaining a molecular remission in MCL,” he said.

All patients reported treatment-emergent adverse events (AEs), including 93% who experienced grade ≥3 AEs. The most common grade ≥3 AEs reported included neutropenia and thrombocytopenia. No patients withdrew because of toxicity.

Before these results can fully impact clinical practice, longer follow-up is needed, Dr. Phillips said. “We are currently planning to enroll another 50 patients without known TP53 mutation as part of a planned expansion,” he added. “We will compare our outcomes to the established chemotherapy regimens which have reported median PFS approaching or exceeding 10 years.”

He also noted that the cost of the agents cannot be overlooked.

“While lenalidomide will be off patent soon, the cost of venetoclax will have to be considered when evaluating this regimen against some of the other options available,” he said. “This will be mitigated to some extent as all the oral agents are given for a finite time period as part of the protocol.”

Study authors report relationships with AbbVie and Genentech, the manufacturers of venetoclax.


Phillips TJ, Danilov AV, Bond DA, et al. The combination of venetoclax, lenalidomide, and rituximab in patients with newly diagnosed mantle cell lymphoma induces high response rates and MRD undetectability. Abstract #7505. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.