Expectant Management of Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue (BALT)
Authors: Leyfman Yan , Joffe Erel , Drill Esther , Rajeeve Sridevi , Zelenetz Andrew D. , Palomba Maria Lia Lia , Moskowitz Craig H. , Portlock Carol S. , Noy Ariela , Horwitz Steven M. , Moskowitz Alison J. , Hamlin Paul A. , Matasar Matthew J , Kumar Anita , von Keudell Gottfried R. , Batlevi Connie Lee , Younes Anas , Straus David J. 
Published: November 2019

Bronchial-associated lymphoid tissue lymphoma (BALT) is a rare subtype of extranodal marginal zone lymphoma that is often diagnosed incidentally, without symptoms or compromise of pulmonary function. It usually progresses slowly . However, in contrast to other subtypes, oncologists may feel compelled to initiate treatment at the time of diagnosis, because of concern for progression resulting in irreversible lung damage. It is unclear, in many cases, whether the morbidity of treatment would be greater than that of the lymphoma itself. To address this issue, we compared patients with BALT initially managed expectantly to those receiving front-line treatment.
A retrospective single institutional review of newly diagnosed primary BALT treated at Memorial Sloan Kettering Cancer Center between 1995 and 2017 was performed. Patients with evidence of extra-thoracic disease (except for isolated bone marrow involvement) and those with concurrent malignancy were excluded. Expectant management (active surveillance) was defined as a management plan of observation rather than treatment at diagnosis and at least 3 months of follow-up from completion of all diagnostic workup until initiation of subsequent therapy if necessary. Surgical Resection referred to complete resection of all disease lesions for diagnosis. Overall (OS) and event-free survival (EFS) were determined from diagnosis as time to treatment or death of any cause, among patients with surgical resection, active surveillance, and time-to-next treatment among those treated at diagnosis with systemic immuno/chemo-immunotherapy (systemic treatment).
Medical records of 200 consecutive patients with MZL involving the lung were reviewed, and 127 met the criteria for primary BALT. Of the remaining 73 patients, 25 had concurrent malignancy and 48 had extra-thoracic disease. Nearly half (48%; n=61) had initial active surveillance, 40% (n=51) surgical resection, and 12% (n=15) systemic treatment at diagnosis. Median age was 65 years (IQR 54-74). Females predominated (64%, n=81). Rates of current or prior smoking (61%; n=78) and of autoimmune/connective tissue disease (20%; n=26) were high. Nearly half of the cases with concurrent cancers were primary carcinomas of the lung (n=11). Most patients presented with a single lesion (76%; n=96) with median size 2.5 cm (IQR 1.6-3.6) and without lobar predominance. A minority (5.5%; n=7) presented with thoracic nodal involvement, while 25% (n=32) presented with pleural involvement or effusion. Overall, few patients had bone marrow involvement, B symptoms, cytopenia or elevated LDH.
With a median follow-up of over 60 months (IQR 25 - 107), estimated 6-year OS for the entire cohort was 92% (0.86, 0.98). Notably, high survival rates were found in all 3 groups (Figure 1). Estimated 6-year survivals were 88% (0.77,1.00) for patients with disease remaining after biopsy managed by active surveillance, 100% with initial complete diagnostic excision (surgical resection) and 78% (0.59, 1.00) for those with initial systemic treatment who likely had extensive initial disease and/or symptoms. Active surveillance patients had a shorter EFS than surgical resection patients but not than systemic treatment patients (6yEFS 63% vs. 74% vs. 57%, respectively; p=0.006). Estimated 6-year EFS (survival without treatment) of patients initially managed by active surveillance was 63% (95% CI 0.5-0.8), and 12% required only a single line of therapy (6yEFS2 85%; 95% CI 0.7-1.0).
In conclusion, BALT is an indolent disease in most patients that can be managed expectantly and may not require therapy for many years. Slightly better survival in patients with fully resected disease could represent a selection bias of earlier detection or biologically less active disease. Initial observation of the pace of the disease in asymptomatic patients may clarify the minority who require treatment and avoid or delay its potential risks in the majority.
Figure 1

Disclosures
Rajeeve: ASH-HONORS Grant: Research Funding. 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