Concurrent Radiation Therapy With the Antibody-Drug Conjugates Brentuximab Vedotin and Polatuzumab Vedotin

Abstract

Brentuximab vedotin (BV) and polatuzumab vedotin (PV) are antibody-drug conjugates targeting CD30 and CD79B, respectively, approved for the treatment of select T- and B-cell lymphomas. Safety data to inform the use of concurrent radiation therapy (CRT) with BV or PV is lacking.We retrospectively reviewed 31 patients (pts) who received CRT with BV or PV from 5/2018 to 1/2021. We defined CRT as infusion within 3 weeks prior to or concurrent with RT. Timing of toxicity (CTCAE v5.0) was classified as pre-RT (within 1 month prior to RT), acute (start to 1 month post-RT), and subacute (2-3 months following RT), censored at subsequent systemic therapy. Statistics were performed using Mann-Whitney U and Chi-squared tests.Of 31 pts, 20 (65%) received BV and 11 (35%) received PV. Median age at CRT was 55 (range 27-88), and 14 pts were female (45%). 26 pts (84%) had stage III-IV disease at the time of CRT. The most common diagnoses were mycosis fungoides (12 pts, 39%; 7 with large cell transformation) and diffuse large B cell lymphoma (10 pts, 32%). Pts received a median of 4 lines of prior systemic therapy (range 0-8). 22 pts received prior RT courses (median 1, range 1-6). Fourteen pts received combination regimens with BV or PV: bendamustine and rituximab (R) (5, 16%); cyclophosphamide (C) (± R) (3, 10%); R alone (5, 16%); and C with doxorubicin (1, 3%). Eleven pts (35%) were treated with electrons targeting skin, with a median dose of 12 Gy (range 4-32). Twenty pts (65%) were treated with photons to 32 sites, with a median dose of 25 Gy (range 9-44); treatment sites included the spine (14 pts, 45%), abdomen/pelvis (9 pts, 29%), and brain (3 pts, 10%). Median percent bone marrow (BM) treated was 6.6 (range 0-18.3). The rate of grade 2 or higher (G2+) hematologic toxicity (HT) was 45% (14/31) pre-CRT vs. 79% (23/29) in the acute setting (P = 0.044) and 71% (10/14) in the subacute setting (P = 0.29). There was no significant change in acute or subacute pain, fatigue, diarrhea, neuropathy, or hepatotoxicity following CRT. Acute G2+ HT was associated with pre-RT G2+ HT (P = 0.019) and more lines of prior systemic therapy (P = 0.011). Percentage of BM irradiated was not significantly associated with acute G2+ HT (P = 0.09). Age, concurrent chemotherapy with BV or PV, prior RT courses, RT dose, and RT modality were not associated with G2+ HT. Six pts (19%) were bridged to stem cell transplant at a median of 26 days (IQR 16-52). 12 patients (39%) received subsequent systemic therapy for progression at a median of 81 days (IQR 25-87). Median time to progression or last follow-up was 72 days (IQR 20-113). At last follow-up, 18 pts (58%) were deceased; median overall survival from CRT was 177 days (95% CI 92-263).CRT with BV or PV was overall well tolerated. We observed HT, particularly in patients with cytopenias prior to RT. Care should be taken during RT planning to reduce this risk if possible.