Safety of concurrent radiation therapy with the antibody-drug conjugate polatuzumab vedotin in relapsed or refractory aggressive B-cell lymphomas.

Abstract

Polatuzumab vedotin (PV) is a CD79b-targeted antibody-drug conjugate (ADC) used in patients with high grade B-cell lymphomas. While its safety profile is well-established, limited safety data exist on concurrent administration with radiation therapy (RT). This study evaluates the toxicity profile of PV administered concurrently with RT (PVRT). We retrospectively analyzed patients with B-cell lymphomas who received PVRT (PV within 3 weeks prior or during RT) at a single institution. Toxicities were graded per CTCAE (Common Terminology Criteria for Adverse Events) v5.0 and categorized as pre-RT, acute (start of RT to 1-month post-RT), or subacute (2-3 months post-RT). Associations were assessed using Mann-Whitney U and chi-squared tests. Twenty-one patients were included with a median age of 57 years. Patients had received a median of 4 lines of prior systemic therapy, and 48% received additional concurrent systemic therapy with PVRT. Acute grade 3 or higher (G3+) hematologic toxicity (HT) was associated with G3+ HT prior to PVRT (p = 0.03). Increase in acute HT grade, but not subacute HT grade, was associated with RT dose (p = 0.03). Grade 2+ neuropathy prior to PVRT was associated with acute G2+ neuropathy after PVRT (p = 0.001). other nonhematologic toxicities (pain, fatigue, diarrhea) and elevated liver function tests (LFTs) pre-PVRT were not associated with acute/subacute toxicity. Median follow up was 3.5 months with 86% of patients deceased; median follow-up for surviving patients was 20 months (interquartile range (IQR) 7-39 months). Delivery of PVRT is feasible with low rates of new onset toxicity. Acute HT was strongly associated with prior HT, though RT dose was associated with increased acute, but not subacute, HT grade. No unexpected toxicity was observed. Further prospective studies are needed to optimize integration of PV with RT.