Supplementing an aggressive chemotherapy regimen with Zevalin (ibritumomab tiuxetan) is safe and provides improved clinical response in patients with intermediate or high-risk follicular lymphoma, results from a Phase 2 clinical trial show.
The study, “Management of newly diagnosed high‐risk and intermediate‐risk follicular lymphoma with 90Y ibritumomab tiuxetan in a phase II study,” appeared in the journal Hematological Oncology.
Patients with follicular lymphoma can be divided into three major risk groups, each with a very different prognosis. While 90% of low-risk patients live for five years or more, only 53% of high-risk patients live that long. This suggests that more effective therapies are needed for intermediate and high-risk follicular lymphoma patients.
Zevalin, a radioimmunotherapy by Spectrum Pharmaceuticals, combines a radioactive substance with a cancer-targeting antibody. It is already approved in combination with Rituxan (rituximab) for certain follicular lymphoma patients.
In an attempt to improve the outcomes of intermediate and high‐risk patients, researchers at the Sunnybrook Health Sciences Centre in Toronto evaluated a new first-line treatment, which consists of R-CHOP — an aggressive chemo‐immunotherapy regimen with Rituxan, cyclophosphamide, vincristine, doxorubicin, and prednisone — supplemented with Zevalin, followed by standard Rituxan maintenance over two years.
The Phase 2 trial (NCT01446562) analyzed changes in overall response rate, the portion of patients with tumor size reduction over a certain period of time, and progression-free survival (PFS) — the period of time during and after treatment without disease worsening or death.
Minimal residual disease (MRD), which refers to the presence of residual cancer cells after treatment, as well as toxic effects and changes in immune B-cell numbers and function were also assessed.
The trial enrolled 33 patients. After five years, 88% of intermediate-risk patients and 83% of high‐risk patients were still alive, representing an improvement over prior data.
Additionally, 85% of patients achieved a complete response three months after treatment, including six patients who had only achieved a partial response before receiving Zevalin. All but two patients responding to therapy had ongoing disease regression up to one year after being treated with Zevalin.
At five years, 79% of intermediate and 58% of high-risk patients were alive and had not experienced disease progression, which is an improvement over standard bendamustine and Rituxan, the investigators noted.
“This treatment provides a reasonable role for [Zevalin] to consolidate higher risk FL [follicular lymphoma] patients who with current approaches are destined for shorter PFS,” the researchers wrote.
Nine of 19 patients with minimal residual disease remained in complete remission after a median follow‐up of four years.
Blood-related toxic effects after Zevalin administration were mostly mild and moderate (grades 1 and 2). However, asymptomatic severe or potentially life-threatening (grades 3 or 4) low platelet count and low levels of neutrophils were observed in 11%‐36% and 10%‐24% of patients, respectively.
Myelodysplastic syndrome, a group of disorders caused by poorly formed or functioning blood cells, occurred in one patient after four years of treatment. A substantial number of patients had sustained B-cell reduction and low immunoglobulin levels after treatments, but maintained previous immunity to rubella or mumps.
“Consolidation with [Zevalin] prior to [Rituxan maintenance] is feasible, safe, and promising given the PFS and MRD status of complete responders but would need to be compared in a randomized trial,” the scientists concluded.