NEW ORLEANS—Treatment with the RiBVD regimen—rituximab, bendamustine, bortezomib [Velcade], and dexamethasone—results in a high response rate in treatment-naïve elderly patients with mantle cell lymphoma (MCL), preliminary results of the LYSA trial reported at the 55th American Society of Hematology Annual Meeting and Exposition.
Interim analysis after four cycles of RiBVD demonstrated a complete response/complete response unconfirmed (CR/Cru) by independent review of 60%, “which has been shown to be predictive of a long duration of response,” said Rémy Gressin, MD, of University Hospital Grenoble, Grenoble, France, on behalf of the LYSA Group.
The prospective phase 2 “Lymphome Du Manteau 2010 SA” trial enrolled 76 patients older than 65 years of age or ineligible for autologous stem cell transplant (ASCT) newly diagnosed with untreated MCL between November 2011 and December 2012. Patients were CD20-positive, Easter Cooperative Oncology Group (ECOG) performance status 0-2, AA stage II-IV, and had no CNS involvement or active HBV/HCV/HIV infection.
The primary end point was effect of the RiBVD regimen—rituximab 375 mg/m² IV on day 1, bendamustine 90 mg/m² IV on days 1 and 2, dexamethasone 40 mg/m² IV on day 2, and bortezomib 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11 every 4 weeks—on progression-free survival (PFS). Primary prophylaxis with valacyclovir was mandatory for herpes virus reactivation; however, there was no recommendation for pneumocystosis. Secondary objectives included toxicity and response after four cycles, toxicity and response after six cycles, and overall response.
Of the 70 patients evaluable for analysis, 49 were male. Median age was 72 years (range, 64-83 years). AA stage II/III-IV was 5/65, ECOG PS 0-1/2 was 59/11, and Mantle Cell Lymphoma International Prognostic Index score low/intermediate/high was 3/19/48.
A total of 61 patients responded, for an overall response rate of 87%; 42 in CR/Cru (60%), and 19 in partial response (PR; 26%). Three patients progressed after three cycles, Dr. Gressin reported. After four cycles, 61 patients were analyzed by PET scan, which found 39 (57%) attained a CR (30 in CR/CRu and nine in PR) and 21 remained PET positive (11 patients CR/CRu, 10 in PR and one stable disease).
Of the 280 planned cycles of RiBVD, 271 (96%) were administered. Seven patients stopped treatment prematurely, three due to disease progression and one for toxicity; three patients died. All but one of the planned bendamustine doses (n = 542) were administered. Dosing was modified 17 times (3%), primarily for hematologic toxicity (n=14). ninety-four percent (1,028/1,084) of the planned bortezomib doses were administered, which was prematurely stopped for neurotoxicity (10 instances) or hematologic side effects (46). Rituximab was not administered in four instances.
Toxicity appeared acceptable and manageable; however, four patients (6%) died, one from pneumonia (cycle 1, 77 years of age), two from cardiac arrest (cycle 2, 71 years and cycle 4, 71 years), and one following progressive multifocal leukoencephalopathy (cycle 3, 65 years); only the latter death was related to study treatment, rituximab. Subcutaneous bortezomib showed markedly decreased neurotoxicity compared to the intravenous form, he reported.
Molecular response showed 29 (85.3%) of 34 patients were minimal residual disease negative in blood and 22 (84.6%) of 26 in bone marrow.
Hematologic toxicites included neutropenia (46% grade 3/4), febrile neutropenia (7% grade 3/4), and anemia (7% grade 3). Other toxicities included liver (4% grade 3), neuropathy (13% grade 3), fever (9% grade 3/4), rash (4% grade 4), lung (4% grades 3/4), cardiac (8% grades 3/4), and glycemia (4% grade 3). No pneumocystosis or cytomegalovirus reactivation, alopecia, visual, or ear toxicities were reported.
In 14 of the 16 patients, grade 2 or 3 neuropathy occurred after cycle 3. There was no correlation with age, and the neuropathy was reversible in 11 patients.
Final results, including whether these response rates convert to better PFS, are anticipated within 6 months, Dr. Gressin concluded.