Addition of Ofatumumab to Aggressive Chemotherapy Regimen Yields High Response Rates in Newly Diagnosed Mantle Cell Lymphoma

Article

Treatment with ofatumumab plus an aggressive regimen of chemotherapies resulted in a response rate of more than 80% in patients with newly diagnosed mantle cell lymphoma.

The use of ofatumumab plus an aggressive chemotherapy regimen of hyper-fractionated cyclophosphamide, doxorubicin, vincristine and dexamethasone (HyperCVAD) as well as high-dose methotrexate and cytarabine (HD-MA) led to high response and minimal residual disease negativity rates in patients with newly diagnosed mantle cell lymphoma.

Of note, a presence of minimal residual disease indicates that a patient has a small number of cancer cells remaining in the body during or after treatment. A patient is deemed to be minimal residual disease-negative if blood and/or bone marrow tests show no residual signs of cancer.

“For young, transplant-eligible patients with (mantle cell lymphoma) requiring therapy, high-dose cytarabine-based intensive chemotherapy regimens followed by consolidative autologous stem cell transplant and posttransplant (Rituxan [rituximab]) remain the standard of care,” the study authors wrote alongside the findings, which were published in the journal Cancer.

Previously, research has shown that a molecular response following induction (frontline0 treatment with a Rituxan-based regimen — regardless of the therapies used or response rates — predicted prolonged duration of response to therapy. Additionally, data from another study showed that Rituxan, an anti-CD20 monoclonal antibody, induced a molecular remission in 48% of patients. Those results, according to the study authors, indicated a further need to find more effective anti-CD20 monoclonal antibodies for the front-line treatment of patients.

The study authors noted that ofatumumab appeared to be a more potent anti-CD20 monoclonal antibody than Rituxan in several pre-clinical trials, which ultimately led to this single-institution phase 2 study.

The trial included 37 patients (median age, 60 years; 73% male) who were treated with ofatumumab plus HyperCVAD/HD-MA for four or six cycles, followed by high-dose chemotherapy and autologous stem cell transplant. Measuring the overall response rate (percentage of individuals who derive a partial or complete response from treatment) was the main goal of the study.

Other goals included observing minimal residual disease negativity, progression-free survival (time during and after treatment when a patient is alive, but the disease does not get worse) and overall survival.

Most of the patients — who were enrolled onto the trial between March 2012 and November 2017 — had advanced/stage 4 disease (86%).

Of the 37 patients who received the combination, 29 were able to complete the induction therapy. Of those, 24 were eligible to receive high-dose chemotherapy and autologous stem cell transplant.

At the end of the treatment induction, the use of the ofatumumab-based regimen induced an overall response rate of 89% with 46% of patients achieving a complete response.

The findings also showed that the overall response rate 100 days after autologous stem cell transplant was 81%.

Nine patients remain in remission at a median follow-up of four years.

MRD Negativity

Blood and/or bone marrow samples were available in 28 patients who were enrolled on the trial. At the start of the trial, 91% of patients had detectable minimal residual disease in their blood and 80% in their bone marrow. However, after the first two cycles of therapy, the minimal residual disease rate was 78%. The minimal disease negativity rate jumped to 96% following the induction cycles of study drug, and although it dipped slightly following autologous stem cell transplant, it was still 89%.

The study authors also observed that patients who obtained minimal residual negativity early in the induction cycle (after two cycles) were more likely to achieve an improved progression-free survival. The results, however, did not show a significant benefit in terms of overall survival.

Side Effect Profile

More than half of the patient population (67.6%) experienced a serious or severe drug-related side effect. Three deaths occurred because of complications to therapy. Most of the serious and severe side effects were related to the blood and included thrombocytopenia (low platelet count; 78.4%), anemia (73%) and neutropenia (an abnormally low white blood cell count; 43.2%).

First of its Kind

“To our knowledge, this is the first study to report the safety and efficacy of ofatumumab with an aggressive chemotherapy backbone in patients with mantle cell lymphoma,” the authors concluded.

“Our study suggests that addition of ofatumumab to HyperCVAD/HD-MA was well tolerated and yielded high response rates at the end of induction in patients with newly diagnosed mantle cell lymphoma. Despite high rates of (minimal residual disease) negativity at the end of induction therapy, the responses were not durable and survival outcomes appear lower than historical cohorts after four years of follow-up, likely because of a higher number of patients with high-risk disease in our study.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.

Related Videos
Cirmtuzumab Combinations Show Potential in Treatment of Mantle Cell Lymphoma
Related Content