Orlando, Florida—Data being presented at the 2019 ASH Annual Meeting show front-line ibrutinib therapy plus rituximab as having a high efficacy rate in patients with indolent clinical forms of mantle-cell lymphoma (MCL).

“The aim of this study was to propose a frontline tailored treatment for indolent clinical forms with a chemo-free regimen, ibrutinib in combination with rituximab. In addition, an extensive genomic study was associated to gain biological insight into these clinical forms,” explained Eva Gine, MD, Hematology Department, Hospital Clinic of Barcelona, Spain, and colleagues.

A total of 40 treatment-naïve patients (median age, 65.7 years) with indolent clinical forms of MCL were enrolled in the multi-center, single-arm, open-label, phase 2 trial.

Eligibility criteria included having no symptoms attributable to MCL and stable disease without the need for therapy for at least 3 months, and patients were allowed to participate if they had leukemic nonnodal or nodal forms.

Study participants were given ibrutinib 560 mg daily and rituximab 375 mg/m2 (4 weekly doses during the first 28-day cycle, followed by day 1 of cycles 3, 5, 7, and 9, for a total of 8 doses). Following 2 years of treatment, ibrutinib could be discontinued if the patient had negative MRD for at least 6 months.

The primary end point of the study was complete remission (CR) rate after 12 cycles. Prior to receiving treatment, patients were observed for a median of 7.6 months, and they were followed-up with for a median of 19 months.

“Efficacy data of the first 33 patients evaluable after 12 cycles of treatment are reported here, including two patients who were discontinued before cycle 12 due to related toxicity,” Dr Gine et al noted.

Overall, responses were achieved by 27 patients, yielding an overall response rate (ORR) of 82% and a CR rate of 75%. The rate of undetectable MRD achieved after 12 cycles was 87% in patients who had CRs and evaluable MRD (n = 23), and only 1 patient ended up with MRD positivity at cycle 24. MRD-negativity was maintained in 12 patients, 9 of whom discontinued ibrutinib therapy per protocol; 3 patients had to have their treatment interrupted earlier because of intolerance.

As of the point of data cut-off, all patients responding to therapy maintained their responses across a median follow-up time frame of 25 months. Dr Gine et al estimated the 15-month progression-free survival rate to be 96% (95% CI, 89-100).

Serious adverse events (eg, cutaneous rash, severe aplastic anemia, pancreatic adenocarcinoma, and lumbar fractures) led to study withdrawal for 4 patients. A further 21 adverse events of grades 3 and 4 were documented and related to Ibrutinib therapy, including hematologic toxicity in 7 patients, gastro-intestinal intolerance in 4 patients, arthralgias in 1 patient, atrial fibrillation in 1 patient, and asthenia in 1 patient.

“In indolent clinical forms of MCL frontline ibrutinib in combination with rituximab has a high efficacy, including undetectable MRD in the majority of cases, with a predictable toxicity profile,” Dr Gine and colleagues concluded.—Hina Porcelli

Gine E, de Fatima De La Cruz M, Grande C, et al. Efficacy and Safety of Ibrutinib in Combination with Rituximab As Frontline Treatment for Indolent Clinical Forms of Mantle Cell Lymphoma (MCL): Preliminary Results of Geltamo IMCL-2015 Phase II Trial. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 752.