Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma.

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

Impact of conditioning chemotherapy on lymphocyte kinetics and outcomes in LBCL patients treated with CAR T-cell therapy.

Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 109/L (range, 0.01-2.75 × 109/L) and was significantly higher in patients who achieved complete response (p = 0.04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.4, 95% CI 0.2-0.8, p = 0.007). Low DLIx was independently associated with shorter progression-free (p = 0.02) and overall survival (p = 0.02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL. The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.

Day 30 SUVmax predicts progression in patients with lymphoma achieving PR/SD after CAR T-cell therapy.

About 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)-computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day -5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P = .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P < .001); all patients with D30 SUVmax ≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P = .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

Human herpesvirus 6 myelitis after chimeric antigen receptor T-cell therapy.

This article reports a fatal case of human herpesvirus 6 (HHV-6) myelitis following CD19-targeted chimeric antigen receptor T-cell therapy. Infection from HHV-6 reactivation after haematopoietic stem cell transplant is established, and outside of this population is limited to case reports. The patient developed cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome that responded to corticosteroids both clinically and on imaging. Subsequently, ascending flaccid paralysis developed, leading to neuromuscular respiratory failure and, ultimately, death. Disease progression was refractory to foscarnet and multiple immunomodulating agents. HHV-6 should be considered in patients with encephalitis and myelitis after adoptive T-cell therapy.

CRP and ferritin in addition to the EASIX score predict CAR-T-related toxicity.

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.

Breast implant-associated anaplastic large cell lymphoma: clinical follow-up and analysis of sequential pathologic specimens of untreated patients shows persistent or progressive disease.

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can involve surrounding tissues, spread to regional lymph nodes, and rarely metastasize to distant sites. The aim of this study was to assess sequential pathologic specimens from patients with breast implant-associated ALCL to better understand the natural history of early-stage disease. To achieve this goal, we searched our files for patients who had breast implant-associated ALCL and who had undergone earlier surgical intervention with assessment of biopsy or cytologic specimens. We then focused on the patient subset in whom a definitive diagnosis was not established, and patients did not receive current standard-of-care therapy at that time. We identified a study group of ten patients with breast implant-associated ALCL in whom pathologic specimens were collected 0.5 to 4 years before a definitive diagnosis was established. A comparison of these serial biopsy specimens showed persistent disease without change in pathologic stage in three patients, progression in five patients, and persistence versus progression in two patients. Eventually, six patients underwent implant removal with complete capsulectomy and four underwent partial capsulectomy. Seven patients also received chemotherapy because of invasive disease, three of whom also received radiation therapy, two brentuximab vedotin after chemotherapy failure, and one allogeneic stem cell transplant. Eight patients achieved complete remission and two had partial remission after definitive therapy. At time of last follow-up, six patients were alive without disease, one had evidence of disease, one died of disease, and two patients died of unrelated cancers. In summary, this analysis of sequential specimens from patients with breast implant-associated ALCL suggests these neoplasms persist or progress over time if not treated with standard-of-care therapy.

Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma.

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy-associated toxicities.

Outcome of relapsed and refractory nodular lymphocyte-predominant Hodgkin lymphoma: a North American analysis.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow-up after initial diagnosis of 14 years (range, 0·5-46 years), median progression-free survival after front-line treatment (PFS-1) was four years. Second-line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high-dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five-year PFS after second-line therapy (PFS-2) was 68% [95% confidence interval (CI), 54-79%] but the five-year overall survival (OS) after second-line therapy (OS-2) remained excellent, at 94% (95% CI, 85-99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de-escalation are needed.

Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on two clinical trials, ZUMA-1 (clinicaltrials gov. Identifier: NCT02348216) and ZUMA-9 (clinicaltrials gov. Identifier: NCT03153462). Complete blood counts, lymphocyte subsets, and immunoglobulin levels were measured serially until month 24 or progression. Fifteen (48%) patients had grade 3-4 cytopenia, including anemia (five, 16%), neutropenia (nine, 29%), or thrombocytopenia (13, 42%) at day 30. Cytopenia at day 30 was not significantly associated with later diagnosis of myelodysplasia. Among patients with ongoing remission, grade 3-4 cytopenia was observed in one of nine (11%) at 2 years. While peripheral CD8+ T cells recovered early, CD4+ T-cell recovery was delayed with a count of <200/mL in three of nine (33%) patients at 1 year and two of seven (29%) at 2 years. Immunoglobulin G levels normalized in five of nine (56%) patients at 2 years. Thirteen (42%) patients developed grade 3-4 infectious complications, including herpes zoster and Pneumocystis jiroveci pneumonia. These results suggest the need for prolonged monitoring and prophylaxis against opportunistic infections in these patients, to improve the longterm safety of axicabtagene ciloleucel therapy.

Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Hodgkin lymphoma is potentially curable. However, 15-35% of older patients (ie, >60 years) have a lower response rate, worse survival outcomes, and greater toxicity than younger patients. Brentuximab vedotin and nivolumab exhibit activity in patients with relapsed or refractory Hodgkin lymphoma. We therefore aimed to evaluate the safety and efficacy of brentuximab vedotin and nivolumab in untreated older patients with Hodgkin lymphoma or in younger patients considered unsuitable for standard ABVD (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. METHODS: We did a multicentre, single-arm, phase 2 trial at eight cancer centres in the USA. Previously untreated patients with classic Hodgkin lymphoma were eligible for study enrolment if they were 60 years or older, or younger than 60 years but considered unsuitable for standard chemotherapy because of a cardiac ejection fraction of less than 50%, pulmonary diffusion capacity of less than 80%, or a creatinine clearance of 30 mL/min or more but less than 60 mL/min, or those who refused chemotherapy. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients received brentuximab vedotin at 1·8 mg/kg (dose cap at 180 mg) and nivolumab at 3 mg/kg both intravenously every 21 days for 8 cycles. The primary endpoint was the overall response, defined as a partial metabolic response or complete metabolic response at the end of 8 cycles of treatment. A per protocol analysis was done including all patients who received treatment in the activity and safety analyses. This study is registered with ClinicalTrials.gov, number NCT02758717. FINDINGS: Between May 13, 2016, and Jan 30, 2019, the study accrued 46 patients. The median age was 71·5 years (IQR 64-77), with two (4%) of 46 patients younger than 60 years. Median follow-up was 21·2 months (IQR 15·6-29·9), and 35 (76%) of 46 patients completed all 8 cycles of therapy. At the interim analysis on Oct 11, 2019, the first 25 evaluable patients had an overall response rate of 64% ([95% CI 43-82] 16 of 25 patients; 13 [52%] had a complete metabolic response and three [12%] had a partial metabolic response). The trial was closed to accrual on Oct 14, 2019, after the interim analysis failed to meet the predefined criteria. In all 46 evaluable patients, 22 (48%) patients achieved a complete metabolic response and six (13%) achieved a partial metabolic response (overall response rate 61% [95% CI 45-75]). 14 (30%) of 46 patients had 16 dose adjustments, primarily due to neurotoxicity. 22 (48%) of 46 patients had peripheral neuropathy (five [11%] patients had grade 3 peripheral neuropathy). Grade 4 adverse events included increased aminotranferases (one [2%] of 46), increased lipase or amylase (two [4%]), and pancreatitis (one [2%]). One (2%) patient died from cardiac arrest, possibly treatment related. INTERPRETATION: Although the trial did not meet the prespecified activity criteria, brentuximab vedotin plus nivolumab is active in older patients with previously untreated Hodgkin lymphoma with comorbidities. The regimen was also well tolerated in the majority of patients in this older population. Future trials should be based on optimising the dose and schedule, perhaps combined with other targeted agents that might permit chemotherapy-free strategies in older patients with Hodgkin lymphoma. FUNDING: Seattle Genetics and Bristol Myers Squibb.

Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma.

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.

Pretreatment SUVmax may influence the clinical benefit of BR over R-CHOP in patients with previously untreated FL.

In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of follicular lymphoma (FL), the results were incongruent. We conducted a retrospective matched-pair analysis to compare the outcome of patients with advanced stage FL, receiving frontline BR (N = 73) or R-CHOP (N = 73), matched by age, gender, stage, and FL International Prognostic Index score. On multivariable analysis, baseline maximum standardized uptake value (SUVmax) >13 was associated with use of R-CHOP (p = .001). After a median follow-up of 69 months for the BR arm and 126 months for the R-CHOP arm, 5-year PFS was 80% and 70%, respectively (p = .07). After adjusting for SUVmax >13, the trend for better PFS in BR was not maintained. Prospective studies are needed to validate the role of pretreatment SUVmax as a stratification factor in future randomized therapeutic trials in FL.

De novo CD5+ diffuse large B-cell lymphoma, NOS: clinical characteristics and outcomes in rituximab era.

CD5+ diffuse large B-cell lymphoma (DLBCL), NOS represents a distinct subset of DLBCL associated with poorer outcomes and extranodal disease. We analyzed characteristics and outcomes for 102 CD5+ DLBCL patients diagnosed between 2001-2016. The majority had poor-risk disease based on R-IPI scores; 80% had extranodal disease at diagnosis. CNS relapse occurred 23% of the time. Median PFS and OS was 18.9 months and 112 months, respectively. Four-year PFS rates were 100%, 53%, and 41% for patients with R-IPI scores of very good, good, and poor, respectively. CD5+ DLBCL represents a subset of patients with poor outcomes despite rituximab and anthracycline-based regimens. There is a need for novel therapies and clinical trials for this high-risk group of patients. Given high rates of CNS relapse, better CNS prophylaxis with frontline therapy requires more study.

Emerging treatment options for patients with p53-pathway-deficient CLL.

Over the past 40 years, p53 has been the most widely studied protein in cancer biology. Originally thought to be an oncogene due to its stabilization in many cancers, it is now considered to be one of the most critical tumor suppressors in a cell's ability to combat neoplastic transformation. Due to its critical roles in apoptosis, cell-cycle arrest, and senescence, TP53 deletions and mutations are commonly observed and are often a portent of treatment failures and poor clinical outcomes. This is particularly true in chronic lymphocytic leukemia (CLL), as patients with p53 alterations have historically had dismal outcomes. As such, the tremendous efforts made to better understand the functions of p53 in CLL have contributed substantially to recent advances in treating patients with p53-pathway-deficient CLL.

Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma.

Radiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

A PET Radiomics Model to Predict Refractory Mediastinal Hodgkin Lymphoma.

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUVmax). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.

Outcomes After Reduced-Dose Intensity Modulated Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

PURPOSE: In patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, the standard radiation therapy (RT) dose is ≥30 Gy. We report the outcome of patients treated with reduced dose 24 Gy compared with those treated with ≥30 Gy. METHODS AND MATERIALS: We reviewed results from 32 patients who received a diagnosis of gastric MALT lymphoma between 2007 and 2017 who were treated with involved site RT using intensity modulated radiation therapy (IMRT). Response to therapy was based on post-RT endoscopic biopsy. Freedom from local treatment failure (FFLTF), freedom from treatment failure (FFTF), and overall survival (OS) outcomes were determined. RESULTS: The median age of patients at diagnosis was 58 years. Therapy for MALT was given prior to RT in 14 patients with residual biopsy proven disease documented in all cases (anti-microbial, n=11; rituximab, n=2; rituximab, cyclophosphamide, doxorubicin, vincristine, n=1). One patient received RT (36 Gy) and concurrent rituximab. The median RT dose was 30 Gy; it was 30 to 36 Gy in 66% of patients (n = 21) and 24 Gy in 34% of patients (n = 11). Post-RT biopsy documented a complete response in all patients. Failures occurred in the stomach and duodenum, respectively, at 3.6 and 4.5 years, after 30 Gy. At a median follow-up of 55.2 months (73.8 for ≥30 Gy compared with 28.7 for 24 Gy; P < .001), the 2-year FFLTF, FFTF, and OS were 100%, 100%, and 97%, respectively. No association was found between the lower (24-Gy) dose and FFLTF (P = .819), FFTF (P = .819), or OS (P = .469). CONCLUSIONS: Contemporary RT with involved site targeting using IMRT is associated with high complete response rates for patients with gastric MALT lymphoma, even using reduced doses of 24 Gy. Additional follow-up and increased patient numbers are required to confirm equivalent disease control.