Patients with newly diagnosed mantle-cell lymphoma responded well to a new drug combination containing Venclexta (venetoclax), Revlimid (lenalidomide), and Rituxan (rituximab).
This treatment even led to undetectable amounts of cancer in the blood, according to Tycel Jovelle Phillips, MD, Clinical Associate Professor, Department of Medicine, University of Michigan Rogel Cancer Center, Ann Arbor, who presented results of the study at the 2021 ASCO Annual Meeting.
Mantle-cell lymphoma is a rare type of lymphoma that makes up about 5% to 6% of all new cases of non-Hodgkin lymphoma. Currently there is no standard-of-care treatment for patients with mantle-cell lymphoma, so oncologists typically decide on a patient’s course of treatment based on factors such as the patient’s age or fitness.
Young, fit patients typically receive treatment with intensive chemotherapy, with or without a stem-cell transplant; by contrast, elderly or unfit patients are treated with less toxic regimens, Dr. Phillips said.
The combination of lenalidomide and rituximab has been safe and effective in patients with newly diagnosed mantle-cell lymphoma who are unfit or who cannot have a transplant.
Undetectable Minimal Residual Disease
Dr. Phillips and his colleagues wondered if adding venetoclax to these 2 drugs would improve patient outcomes, and can lead to patients having no sign of cancer, or no minimal residual disease (MRD), meaning there is no evidence of even minimal disease, which is also called “MRD-negative disease,” or “undetectable MRD.”
Venetoclax is an oral drug that has been approved by the FDA for the treatment of patients with several types of leukemia.
“We hypothesized that the combination of venetoclax, lenalidomide, and rituximab would be safe, with the potential to improve overall response rate and time to best response, and could potentially induce MRD-negative disease,” Dr. Phillips said, meaning that patients would not have even minimal disease after they receive this 3-drug combination therapy.
Improved Patient Outcomes
The study by Dr. Phillips and his co-investigators included 30 patients with untreated mantle-cell lymphoma. The patients received 12 cycles of induction (initial) therapy with venetoclax, lenalidomide, and rituximab.
After the initial 12 cycles of this 3-drug combination, the patients continued to receive a 3-year maintenance treatment with the same 3 drugs, which included venetoclax for 12 months, lenalidomide for 24 months, and rituximab for 36 months. Treatment continued unless the cancer progressed.
Of the 30 patients in the study, 28 received the planned initial treatment; 1 patient was removed from the study; and 1 died before the study began. In all, 19 patients completed induction therapy and continued maintenance therapy. A total of 23 patients are currently still receiving treatment, 3 stopped treatment because of progressive disease, and 2 patients stopped treatment for other reasons.
Most patients had advanced-stage cancer, but most were still able to perform everyday tasks.
During the course of treatment, 15 patients required that their dose be delayed, mostly because of side effects, and 10 patients required dose reductions, mostly of venetoclax, but no patient discontinued treatment because of the drugs themselves, said Dr. Phillips.
Within 3 months, 67% of patients had complete disease remission, meaning that they had no evidence of cancer, and 29% of the patients had a partial response to treatment, meaning that their cancer was responding to treatment and they had less cancer cells. By 9 months, most (94%) of the patients had complete remission, and by 1 year, 100% of the patients had complete remission.
“At 3 months, 63% of patients were MRD-undetectable, and this number increased to 77% at 6 months,” Dr. Phillips reported. “At 9 months, 94% of 16 evaluable patients had undetectable MRD, and at 12 months, the vast majority of patients (92%) had undetectable disease.”
Looking at the response to therapy and the MRD data together, Dr. Phillips noted that the longest response to treatment was 24.4 months (for the first patient enrolled in the study), and this patient is still in remission.
As of April 21, 2021, the 12-month rate of time without disease progression was 86%. So by 1 year after treatment, the vast majority of patients in the study had not had disease progression.
The most common side effects were neutropenia (low white blood cell count), thrombocytopenia (low platelets), and diarrhea. Serious side effects were most often neutropenia and thrombocytopenia, and 2 patients had a second cancer during the study.
There were no dose-limiting side effects among any of the patients in the study, meaning that no side effects were serious enough to require dose reduction.
“The combination of rituximab, lenalidomide, and venetoclax was found to be safe, with no dose-limiting toxicities noted,” said Dr. Phillips. “And no patient who obtained undetectable MRD status has relapsed.”
Only 3 patients in the study had progressive disease, and they all had the p53 mutation, a type of gene mutation that may cause cancer cells to grow and spread.
Based on these findings, the investigators plan to expand the original study with the 3-drug combination, but they also intend to exclude patients with p53 mutations. However, Dr. Phillips said that these patients would be included in a second study, with modifications for them and other patients with high-risk cancer features.