Data recently presented at the ASCO Annual Meeting showed that a lower dose of polatuzumab vedotin in combination with rituximab has a similar overall response rate but improved toxicity when compared to a superior dose in patients with relapsed or refractory follicular lymphoma.
“Polatuzumab vedotin is an anti-CD79b antibody-drug conjugate,” Ranjana H. Advani, MD, professor of lymphoma at Stanford University, said in a recent news release. “CD79b is a component of the B-cell receptor and is expressed in nearly all B-cell malignancies. Clinical activity has been observed in relapsed and refractory non-Hodgkin’s lymphoma at doses greater than or equal to 1.8 mg/kg in a phase 1 trial. Subsequently, two dose levels — 1.8 mg/kg and 2.4 mg/kg — were assessed in a phase 2 trial in relapsed and refractory follicular lymphoma, but the optimal duration of therapy is unknown.”
In previous studies, patients treated with 2.4 mg/kg dose polatuzumab vedotin showed signs of toxicity. In this study researchers investigated if the combination of polatuzumab vedotin at lower doses was still therapeutically efficient and could decrease cumulative toxicity.
A total of 35 patients with relapsed or refractory follicular lymphoma who were treated with either 75 mg/m2 rituximab with 1.8 mg/kg (n = 10) or 2.4 mg/kg (n = 25) of polatuzumab vedotin were enrolled. The treatment was performed every 3 weeks and the results collected until there were signs of unacceptable toxicity. At the end, patients were submitted to at least eight treatment cycles, with a median follow-up of 8 and 14 months for 1.8-mg/kg and 2.4 mg/kg patients’ cohort, respectively.
Researchers observed that while the overall response rate was similar in both cohorts (75% for 1.8-mg/kg and 76% for 2.4-mg/kg), after eight treatment cycles, patients treated with the highest dose achieved higher complete response rates – 32% versus 10%. The adverse effects of grade 3 or higher occurred in both cohorts after eight cycles, however, at 2.4-mg/kg more patients discontinued the treatment due to an adverse event at eight cycles (28% versus 25%) and with treatment completion (56% versus 30%).
“Tolerability may be improved by dosing polatuzumab vedotin at 1.8 mg/kg and a fixed duration of eight or fewer cycles,” Advani said. “Efficacy is seen at both dose levels, despite the higher number of complete remission at the higher dose. Polatuzumab may represent a clinical meaningful treatment option at the 1.8-mg/kg dose at the fixed duration of therapy, and studies of this combination of immunotherapy are ongoing in both large cell lymphoma andfollicular lymphoma.”