Study Suggests Treatment May Be More Beneficial Than Observation in Select Patients With Extranodal Follicular Lymphoma

According to a single-institution retrospective study recently published in&nbsp;<em>Clinical Lymphoma, Myeloma &amp; Leukemia,&nbsp;</em>minimally toxic first-line therapies may be beneficial in early extranodal follicular lymphoma compared with observation.

According to a single-institution retrospective study recently published inClinical Lymphoma, Myeloma & Leukemia,minimally toxic first-line therapies may be beneficial in early-stage extranodal follicular lymphoma (FL) compared with observation.

“Our results show that patients who undergo treatment have better progression-free survival (PFS) rates compared with those who are observed only,” wrote the authors, led by radiation oncologist Therese Andraos, MD. “Therefore, using an approach that could control the disease with the least toxicity, which currently includes radiation therapy alone or with rituximab, could be a great option for these patients, while reserving systemic therapy for when the disease relapses or transforms.”

The authors examined data from 37 patients with stage I/II extranodal FL treated at The University of Texas MD Anderson Cancer Center between 2003 and 2013. The patients’ median age was 60.0 years (range, 37-84). Slightly more than half the patients were male (n = 19) and a clear majority had stage I disease (n = 29, 78.4%). Most patients had a Follicular Lymphoma International Prognostic Index score of 0 or 1 (n = 31, 83.8%).

FL was seen in the gastrointestinal tract in 22 patients (59.5%). Of these, 18 patients had small intestine tumors, 2 had pancreatic tumors, and 1 each had liver or colon tumors. The remaining patients had non-GI extranodal FL. This cohort had exceptionally diverse disease, including 3 patients each with vertebral body and salivary gland involvement. One patient each had FL of the nasopharynx, thyroid gland, base of tongue, bronchial wall, buccal mucosa, orbit, and paraspinal tissue.

Most patients received chemotherapy alone as initial treatment (n = 21, 56.8%), while 7 received chemotherapy plus radiation (18.9%). Two patients had radiation alone (5.4%) and 1 had radiation plus rituximab (2.7%). Six patients received observation only (16.2%).

The median radiation dose was 30.6 Gy (range, 23.4-44.0 Gy). About half the patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; n = 16; 57.1%) as their systemic regimen. Five patients received rituximab alone (17.9%). Other regimens included R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone; n = 3; 10.7%), ibritumomab (n = 2; 7.1%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; n = 1; 3.6%), and PCR (pentostatin, cyclophosphamide, rituximab; n = 1; 3.6%).

Of the 22 GI FL patients, 16 received chemotherapy, 2 received chemotherapy and radiation, and 1 received rituximab and radiation. Three patients received observation. Five patients with intestinal disease received surgery prior to adjuvant therapy.

No patients experienced disease transformation during the study period. In the GI group, 6 of 22 patients relapsed; 4 of these were local relapses at the initial site of extranodal involvement. Additionally, 5 of 15 non-GI patients had disease relapse; 3 of these were local relapses.

Andraos et al found that patients who were observed had a significantly higher relapse rate compared with those who received initial therapy (P= 0.021). “The risk of disease relapse did not differ according to treatment strategy in univariate analysis, excluding patients who were observed; however, patients who were observed had a significantly higher progression rate (4/6; 66.6%) compared with those who received any treatment,” they wrote. “After stratifying patients on the basis of the location of their extranodal disease, observation was still negatively associated with a higher risk for relapse especially for those with PFS in the GI cohort (P= 0.055).”

The median follow-up was 69 months (range, 8-157 months). Five-year PFS was 70.4% and overall survival (OS) was 94.4%. Among GI patients, 5-year PFS was 80.4% and OS was 100% (P= 0.314). Non-GI patients had a 5-year PFS of 57.8% and OS of 96.2% (P= 0.163).

Patients who were observed experienced worse PFS than those who received initial treatment (5-year PFS 33.3% vs. 77.6%;P= 0.011), with no difference in OS (P= 0.623). “In patients who received radiation as a part of upfront management, no local relapse was observed, and there was a trend toward improved local control (LC; 5-year LC, 100% vs. 74.0%;P= 0.058), with no significant effect on PFS,” Andraos et al wrote. “Among patients who received RT, there was no difference in PFS rates when stratified according to GI or non-GI involvement (P= 0.513).” No local relapse occurred in either group.

Andraos et al found what they described as “a borderline significant added value” on 5-year PFS in patients who received combination therapy compared to chemotherapy alone (P= 0.067). PFS at 5 years was significantly higher among non-GI patients who received chemotherapy plus radiation (P= 0.033). The authors did not see this same effect in the GI cohort (P= 0.405).

Andraos et al noted that their data do not reflect MD Anderson’s current management of extranodal FL patients. “Because of the data showing excellent outcomes for these patients, we currently typically use a more minimal approach, such as observation or low-dose radiation therapy,” they wrote. “Our findings are in agreement with the overall management of nodal FL for which patient’s treatment strategy does not affect the OS, especially in early stage disease. That made it acceptable to deliver local radiation with minimal toxicity and reserve systemic therapy for when disease relapse occurs in a distant location.”


Andraos T, Ayoub Z, Nastoupil L, et al. Early Stage Extranodal Follicular Lymphoma:Characteristics, Management, and Outcomes. Clin Lymphoma Myeloma Leuk. 19(2)doi: 10.1016/j.clml.2019.02.011[Epub ahead of print].