Low-dose radiation (4 Gy) with/without concurrent chemotherapy is highly effective for relapsed, refractory mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) generally exhibits an aggressive disease course with poor outcomes. Despite inherent radiosensitivity, radiation therapy (RT) is not commonly used for MCL. This study assesses the role of low-dose RT (LDRT) with concurrent chemotherapy in relapsed, multiply refractory MCL. From 2014 through 2018, 19 patients with relapsed, refractory MCL had 98 sites treated with 4 Gy. Median follow-up from initial LDRT was 15.4 months. Patients had received a median 7 courses of chemotherapy since diagnosis, and 58% were ibrutinib-refractory. Of the 98 sites, 76% were refractory to ongoing chemotherapy, and LDRT was delivered with concurrent chemotherapy for 76%. The complete response (CR) rate was 81% at a median 2.7 months post-LDRT. There were no differences in CR despite ibrutinib-refractory disease, prior chemotherapy courses (>5), or tumor size (>3 cm). There were no RT-related toxicities. Overall survival at 1 year following initial LDRT was 90%, and 1-year progression-free survival following last course was 55%. In summary, LDRT is effective for relapsed, multiply refractory MCL, and may be safely delivered with chemotherapy, to multiple sites, and repeatedly without issue. By treating active sites of disease, LDRT can provide durable local control, help achieve remission, and potentially bridge patients to subsequent novel therapies.

Radiotherapy in mantle cell lymphoma: A literature review

“…RT achieves excellent local RR (80%-100%) and a high palliation rate in advanced-stage MCL, even in cases of ibrutinib-refractory and chemo-refractory disease. 14,18 In advanced-stage MCL for which RT is not given with intent to cure, we favor LDRT over higher doses, which may be slightly inferior in terms of RR and local PFS but more convenient to administer and minimally toxic, thus repeatable as necessary for local relapse or for distant progressive disease. RT may also secure 6 to 10 months of freedom from the need for further systemic treatment, thereby bridge refractory patients to subsequent therapies, as well as safely enable treatment breaks for patients recovering from toxicities.…”

“…26 Patients who develop resistance to ibrutinib, have extremely poor outcome, with a median OS of 2.9 to 8.4 months. 27,28 Ning et al 18…”

“…To date, five publications have specifically addressed the topic of RT for patients with systemic MCL (Table 2). [14][15][16][17][18] In those studies, most of the patients were elderly and heavily pretreated, thus reflecting "real-world" experience.…”

“…Haas et al 19 demonstrated that LD-IFRT re-treatment, for non-FL patients, achieved a RR of 100%. Ning et al 18 described four MCL recurrences after LDRT that were salvaged with further RT (three with LDRT).…”

“…for R/R MCL, while Neville et al recorded a median systemic PFS of 6.2 months followingRT 17. Ning et al18 reported that six patients with R/R MCL treated with LDRT, without concurrent systemic treatment, achieved a…”