Lower dose of polatuzumab vedotin safe, effective for follicular lymphoma

CHICAGO — A lower dose of polatuzumab vedotin combined with rituximab yielded comparable overall response rates as a higher dose yet improved toxicity among patients with relapsed or refractory follicular lymphoma, according to study results presented at the ASCO Annual Meeting.

“Polatuzumab vedotin is an anti-CD79b antibody-drug conjugate,” Ranjana H. Advani, MD, professor of lymphoma at Stanford University, said during a presentation. “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.”

Previous studies also have demonstrated cumulative toxicity with the 2.4 mg/kg dose. Thus, researchers sought to compare the safety and efficacy of lower and higher doses of polatuzumab vedotin (anti-CD79b ADC, Genentech) plus rituximab (Rituxan, Genentech/Biogen Idec).

Advani and colleagues assigned 35 patients with relapsed or refractory to 375 mg/m² rituximab with 1.8 mg/kg (n = 10) or 2.4 mg/kg (n = 25) polatuzumab vedotin every 3 weeks until the occurrence of an unacceptable toxicity.

Patients in the higher-dose cohort were older (median age, 68 years vs. 62 years) and had less tumor volume (1,824 mm² vs. 2,655 mm²). Forty percent of patients in the higher-dose cohort and 50% in the lower-dose cohort were refractory to their last treatment.

Researchers compared data at the completion of polatuzumab vedotin treatment with data after eight treatment cycles.

Median follow-up was 14 months for the 2.4-mg/kg cohort and 8 months for the 1.8-mg/kg cohort.

Researchers observed a nearly identical overall response rate in the 2.4-mg/kg cohort (76%) and the 1.8-mg/kg cohort (75%) following eight treatment cycles. However, 32% of the 2.4-mg/kg cohort achieved a complete response compared with 10% of the 1.8-mg/kg cohort. The complete response rate increased to 44% in the 2.4-mg/kg cohort following all cycles but remained at 10% in the 1.8-mg/kg cohort.

Researchers observed a median duration of response of 10 months in the 2.4 mg/kg arm. Median duration of response has not been reached in the 1.8 mg/kg cohort.

Researchers estimated a 61% 12-month PFS rate in the lower-dose cohort and a 66% 12-month PFS rate in the higher-dose cohort.

Similar rates of grade 3 or higher adverse events occurred in the high- and low-dose cohorts after eight cycles (52% vs. 50%). More patients assigned 2.4 mg/kg discontinued treatment due to an adverse event after eight cycles of treatment (28% vs. 25%) and after all cycles (56% vs. 30%).

One treatment-related patient death occurred due to pulmonary congestion in the 2.4-mg/kg cohort. The death occurred 2 months following the initiation of the twelfth treatment cycle.

“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 and follicular lymphoma." – by Cameron Kelsall

Reference:

Advani RH, et al. Abstract 8503. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Advani reports honoraria, travel expense and research funding from Agensys, Allos Therapeutics, Celgene, Elsai, GE Healthcare Genentech/Roche, Idera, Janssen Pharmaceuticals, Millennium, Pharmacyclics and Seattle Genetics. Please see the abstract for a list of all other researchers’ relevant financial disclosures.