ESTRO 2022 - Abstract Book

S993

Abstract book

ESTRO 2022

Radiation therapy had been tested at ablative doses for total body irradiation (TBI) in combination with melphalan (MEL) for multiple myeloma (MM), but was shown to be prohibitively toxic. In order to ameliorate toxicity, total marrow irradiation (TMI), an image-guided organ sparing form of TBI, was given as the sole ablative modality during the second cycle of tandem autologous transplant (TAT) for patients with stable/responsive MM as part of a Phase I-II trial. Herein we provide long- term follow-up. Materials and Methods We enrolled patients with MM in response or with stable disease. Patients had to be ≤ 70 years old and ≤ 18 months from diagnosis of MM. They received MEL 200 mg/m2 and AT (Cycle 1), and, after recovery, TMI (1000-1800 cGy; maximum tolerated dose [MTD]: 1600 cGy) and AT (Cycle 2) followed by maintenance with thalidomide or lenalidomide, and dexamethasone monthly for up to 12 months. TMI target volumes included all skeletal bone except mandible and maxillary bones to minimize oral cavity dose and mucositis. Radiation treatment plans were designed using the Hi-Art Tomotherapy treatment planning system such that a minimum of 85% of the target volumes received the prescription dose. Kaplan-Meier method was used to assess survival. The first patient enrolled in 1/2005 and follow-up was updated through 6/2021. Results A total of 54 patients were enrolled. The median age was 54 years (31-66); 31 patients were male. The median time between MM diagnosis and AT was 8 months (3-16). Durie Salmon stages were: I (N=7), II (N=16), III (N=31) and retrospectively calculated ISS stages were: I (N=32), II (N=15), III (N=7). High-risk cytogenetics [t(4;14) (n=1), a variant of t(4;14), or del 17/p53 (n=4)] were observed in 11% of patients. Forty-four of 54 patients (81.5%) received TAT per-protocol. Thirty patients (55.6%) received TAT at the MTD TMI dose of 1600 cGy. Median follow-up among survivors was 12 years (range: 9.2-15.5+). There were no graft failures. Secondary malignant neoplasms included one each of acute myeloid leukemia, papillary thyroid, prostate, and in situ breast carcinoma, and melanoma, and 4 patients with non-melanoma skin cancers. In intent-to-treat analysis, median PFS and OS were 2.8 years (range: 0.3-15.5+) and 7.7 years (range: 0.5-15.5+), respectively. PFS and OS at 10 years is 20.4% (95% CI 10.9-31.9) and 38.8% (95% CI: 25.9-51.5). For patients enrolled at the MTD of 1600 cGy, the PFS and OS at 10 years were 26.7% (95%CI: 12.6-43.0) and 46.2% (95%CI: 27.8-62.7) and median PFS and OS were 4.0 years (range:0.3-14.1+) and 9.3 years (range: 0.5-14.1+), respectively. Conclusion Ablative dose TMI as part of TASCT showed favorable long-term toxicity and outcomes given the systemic therapies available at the time of trial enrollment. The inclusion of TMI as a conditioning regiment for MM prior to ASCT may warrant further study in the context of modern induction and maintenance therapies. Purpose or Objective The spleen can be a persistent reservoir of disease in NHL and splenic infiltration and associated splenomegaly is a challenging complication. The choice between splenectomy and splenic RT is controversial, with little data to provide guidance in NHL. We aim to assess the tolerability and efficacy of splenic RT in NHL. Materials and Methods We reviewed NHL patients treated from 2002 to 2021 with RT to the spleen. Splenomegaly was defined as vertical length >13cm. Splenic volume was obtained by manual contouring in MIM PACS 6.9.7. PET response was evaluated by Lugano criteria. AEs were retrospectively clinician graded using CTCAE. Significance was assessed with Kruskal Wallis test or T- test. Results 19 patients (11 DLBCL, 5 MZL, 3 MCL) were identified with 21 courses of splenic RT. Median age was 75 (42–94); median KPS was 80 (50–90). Most patients (68%) had splenic only disease. Median splenic height pre-RT was 13.6 cm (6.4–26.6); 12 patients (57%) had baseline splenomegaly. Median splenic volume was 682cc (104–3355). 9 patients (43%) were symptomatic pre-RT (most frequently with pain: n=7, dyspnea: n=4, or nausea: n=4). 90% had any cytopenia before RT with median baseline WBC 5 (2–60), ANC 3 (0–11), Lymph 17 (3–76), Hgb 10 (7–13), and Plt 113 (22–208). RT was performed with definitive (n=7), palliative (n=7), or consolidative (n=4) intent, or as bridging to CAR T cells (n=3). Median dose was 30Gy for DLBCL (10.8–45), and 4Gy for MCL/MZL (0.6–20); 10 patients received ≥ 20Gy. RT was well tolerated with 38% of courses without AEs and 57% with G1-2 AEs. AEs with frequency >10% were G1 fatigue (n=6), G1 anorexia (n=5), G1 nausea (n=5), G1 diarrhea (n=3), and G2 fatigue (n=3). There were no G3-4 AEs. One patient died from respiratory failure secondary to fungal pneumonia in the setting of lymphopenia following splenic RT. Cytopenias were evaluated in the 10 cases for which no chemo was given within 30d of RT. Median nadirs: WBC 3 (1–5), ANC 2 (1–4), Lymph 4 (1–17), Hgb 12 (6–13), Plt 78 (9–182) with 9, 9, 9, 6, and 11 median days from RT start to nadir, respectively. Lymph and Plt were disproportionately affected with Hgb preserved (Fig1; median reduction: WBC 38%, ANC 54%, Lymph 72%, Hgb 2%, Plt 84%; p<0.003). A greater absolute reduction in platelets was seen with ≥ 20Gy (median 107 vs. 68; p=0.02). In 3 patients (14%) cytopenias completely normalized post-RT. 4/11 symptomatic patients (36%) experienced complete relief. Median reduction in splenic volume was 34% (0–90; Fig2). ORR by PET was 80%: 37% CR, 43% PR, 10% SD, 5% PD. With a median follow up of 12mo, median duration of radiographic response was 8mo (0.5–103) with more durable response at ≥ 20Gy (median 35 vs. 5mo, p=0.01). PO-1172 Irradiating the spleen for non-Hodgkin lymphoma: efficacy and tolerance H. Hubbeling 1 , B.S. Imber 1 , N.A. Wijetunga 1 , K.R. Tringale 1 , C. Hajj 1 , J. Yahalom 1 1 Memorial Sloan Kettering Cancer Center, Radiation Oncology, New York, USA

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