Phase 1 study of anti-CD22 antibody-drug conjugate pinatuzumab vedotin with/without rituximab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
This is a phase 1 study using pinatuzumab (anti-CD22 monoclonal antibody conjugated to a microtubule disrupting agent) in relapsed/refractory mature B cell lymphomas and CLL. The aim was to determine the phase 2 dose and evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of pinatuzumab.
This was a phase 1 study with a 3+3 dose escalation design of relapsed/refractory patients with: DLBCL, follicular lymphoma, marginal zone lymphoma or small lymphocytic lymphoma, mantle cell lymphoma or CLL. They did NOT have to have CD22 expressed on tumor cells to be eligible. All patients were >18 years. Initial cohort was enrolled to determine maximum tolerated dose (MTD). An expansion cohort with DLBCL or iNHL was enrolled to determine preliminary efficacy at MTD. An additional cohort was enrolled to determine safety and efficacy of pinatuzumab combined with rituximab. Pinatuzumab was given every 21 days.
91 patients were enrolled, 75 receieved pinatuzumab alone, 16 received pinatuzumab combined with rituximab. Three patients had grade 4 neutropenia at 3.2 mg/kg, one with delayed recovery. Antitumor activity was only seen at doses >= 1.8 mg/kg. The dose selected for phase 2 trials was 2.4 mg/kg every 21 days. Twenty-five percent of patients with DLBCL responded to pinatuzumab (2 CRs and 3 PRs) with PFS of 4 months. There was 1 PR in DLBCL in the group treated with pinatuzumab and rituximab.
This study was done in adult patients (median age was in the 60's) and they did not require demonstration of CD22 expression on tumor cells before enrollment. This makes interpretation of the efficacy results difficult, although one would presume that the majority of the DLBCL patients had CD22 expression. This information is useful to be aware of for relapsed DLBCL (or other mature B cell lymphomas expressing CD22), but may not be directly translatable to the pediatric population.