Retrospective Analysis of Primary Mediastinal Large B-Cell Lymphoma (PMBCL) Treated with Rituximab and CHOP (R-CHOP).
Authors: Novoselac Amory V. , Kunamneni Raghu K. , McMasters Malgorzata , Radevic Miroslav R. , Levine Randy L. 
Published: April 2020

Background: PMBCL is a recognized separate entity within the group of diffuse large B-cell lymphoma (DLBCL) (Harris et al, Blood, 1994) with clinical, pathological and recently described molecular distinctiveness. It typically presents as a bulky mediastinal mass with the SVC syndrome, early stage disease, occurring predominantly in young females. The therapeutic approach has paralleled that of DLBCL consisting of anthracycline based regimens with or without the addition of radiation therapy (RT). In recent years, the use of rituximab has become part of the treatment of DLBCL, with outcome improvement demonstrated in patients &gt;60 years of age (Coiffier et al, NEJM 2002) and recently &lt;60 years of age (Sehn et al, ASH 2003, and Pfreundschuh et al, ASCO 2004). Though commonly used as part of the initial treatment, outcome benefit has not as of yet been established in PMBCL.

Methods: Retrospective analysis of 10 patients with PMBCL diagnosed and/or treated in our institution from September 2000 to October 2003 with R-CHOP.

Results: The median age was 30 (range 22–56). There were 7 female and 3 male patients. Eight patients had a low/low intermediate IPI, and all but one had an elevated LDH. Eight patients had early stage disease (I and II), two had stage III. Beta2 microglobulin was not elevated in the 6 patients for whom results were available. Two patients had B symptoms. Bulky disease (&gt; 10 cm or &gt; 1/3 of the thoracic diameter) was present in 7 patients; SVC syndrome was seen in 3. None of the patients had marrow involvement. Median follow up was 13 months (range 9–47). All patients received 4–6 cycles of R-CHOP. Two patients received maintenance rituximab (one received 4 weekly treatments at 6 months and the other received 4 weekly treatments at 3 and 6 months). RT was given to 6 patients. Eight patients had a complete remission (CR) following R-CHOP and two patients had near CR (&gt; 90% reduction); they subsequently achieved CR after the RT.

Conclusions: Great variations of CR rates in the treatment of PMBCL, ranging from 10 to 95% for anthracycline containing regimens have been reported in the literature. Reported CR rates for CHOP alone range from 45–80% and optimal anthracycline based therapies are still being debated. Regardless of the initial regimen, failure patterns most commonly described in PMBCL were either no response to initial treatment or early progression, typically seen within 6 to 12 months. All of our patients achieved and remain in CR with a median follow up of 13 months. We recognize the limitations of our study (i.e. short median follow up, absence of control group, heterogeneous therapeutic approaches). However, this retrospective analysis demonstrates that the addition of rituximab could potentially contribute to the initial response to CHOP in comparison to traditionally reported CR rates found in the literature. Long term follow up in a larger series is necessary for the assessment of outcome improvement with the addition of rituximab in PMBCL patients.

Charcteristics of 10 PMBCL patients treated with R-CHOP

Median age (yrs) (range) 30 (22–56) Female/Male 7/3 Low IPI Score (total) (%) 8 (80%) High LDH (total) (%) 9 (90%) B Symptoms (total) (%) 2 (20%) Stage I and II (total) (%) 8 (80%) Bulky Disease (total) (%) 7 (70%) SVC Syndrome (total) (%) 3 (30%) High Beta2 microglobulin (total) (%) 0 (0%) Bone Marrow Involvement (total) (%) 0 (0%) RT (total) (%) 6 (60%) CR (total) (%) 10 (100%) Median Follow up (mts) (range) 13 (9–47)