Outcomes and toxicities in patients with diffuse-large B cell lymphoma involving the gastrointestinal tract and digestive organs

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) involving the gastrointestinal (GI) organs is rare, and real-world outcomes after combined modality therapy (CMT) with systemic therapy (ST) and radiotherapy (RT) are not well-characterized, particularly in the contemporary era. We characterized outcomes in a large cohort of GI-DLBCL patients treated with ST alone or CMT.

Methods: Patients with GI-DLBCL treated at a single institution were retrospectively reviewed. Kaplan-Meier and Cox regression models estimated survival. Multivariable analyses were conducted using the Cox proportional hazards model.

Results: Of 204 patients, gastric involvement was most common (63%). Most presented with early-stage disease (61%). All patients received ST and 65 patients (32%) received RT, 88% as part of first-line CMT. Median dose was 36 Gy (IQR 30.6-39.6) in 18 fractions (IQR 17-22). Median follow-up was 46 months. Five-year overall survival (OS) and progression-free survival (PFS) was 88% and 84%, respectively; complete response (CR) rate was 82%. Improved OS associated with low IPI (p=0.001), fewer chemotherapy lines (p<0.001), early stage (p<0.006), and CR (p<0.001). Survival did not differ by RT receipt (p>0.25). Only early stage and CR correlated with improved OS on multivariable analysis. Stomach-directed RT vs. RT to other sites correlated with improved PFS and OS (p<0.04). Patients with early stage DLBCL treated with CMT in the post-rituximab era had equivalent OS vs. ST alone, even with fewer chemotherapy cycles (p<0.02; median of 4 with RT vs. 6 cycles without). Fifty patients had bulky disease (≥7.5 cm), of whom 18 (36%) had early stage disease. Among patients with bulky disease, 5 (10%) developed relapse at the initial site of disease bulk. Four of the 5 patients did not receive consolidative radiation. Among these 4 patients, 3 relapsed only in their initial site of bulky disease. Of 191 patients with luminal GI-DLBCL, n=4 (2.1%) developed perforation; only one received RT. Acute Grade 3 toxicities were reported in 41.2% of patients, and 12 (5.8%) patients had late Grade 3 toxicities, 99% attributed to chemotherapy.

Conclusion: GI-DLBCL patients have favorable outcomes after CMT with minimal late toxicity. CMT may be offered with abridged systemic regimens with equivalent outcomes. Stomach directed-RT may mitigate relapse risk associated with incomplete disease response or bulky disease.

Keywords: DLBCL; GI-DLBCL; diffuse large B-cell lymphoma; gastrointestinal; radiation therapy; radiotherapy.

Figure 1

Involved sites of disease within the GI tract among all patients. Stomach was the predominant site of disease, followed by small bowel, and then colon/rectum, followed by other minor sites, including gallbladder, esophagus, liver, and pancreas.

Figure 2

Survival outcomes of patients with DLBCL of the GI tract. Overall survival of the full cohort (A), stratified by stage (B), and receipt of chemotherapy vs. chemoradiation (C). Also depicted are progression-free survival of the full cohort (D), as well as analyses stratified by stage (E), and chemotherapy vs. chemoradiation disposition (F). *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Figure 3

RT receipt and early-stage disease are associated with reduced number of cycles of systemic therapy. Comparison of the number of systemic therapy cycles received by patients in the post-rituximab era in histograms (left) and violin plots (right, for statistical display), comparing (A) treatment strategy with either systemic therapy (ST) alone vs. combined modality therapy (CMT) for patients with early-stage disease, or (B) limited vs. advanced stage of disease. Statistical analysis was via Mann-Whitney U, *p<0.05, **p<0.01, ***p<0.001. Median represented by the thick dashed line, and quartiles by the thin dashed lines.

Figure 4

Provider-reported treatment-related toxicities in the treatment of DLBCL of the GI tract. Acute (A) and chronic (B) chemotherapy-associated toxicities graded by the CTCAE v5.0, as well as acute (C) and chronic (D) radiation-related toxicities are shown below.