Pattern of Single Agent Rituximab Usage in Indolent Lymphoma and CLL beyond GELF and NCI Criteria.
Authors: Cohler Cheryl , Brick-Turin Yael , Hamlin Paul , Portlock Carol , Zelenetz Andrew D. , Noy Ariela 
Published: October 2019

Abstract
The GELF criteria and NCI guidelines are accepted for treatment initiation for indolent lymphomas and CLL. However, the lower toxicity of single agent rituximab (SAR) compared with chemotherapy may affect treatment initiation. We sought to evaluate what criteria hematologists (n=12) in our institution used when treating indolent lymphoma and CLL with SAR.
Methods: A complete data set of all patients(pts)receiving rituximab (R) at MSKCC from 05/02 through 05/07 was compiled. Pts were eligible for this study if they received SAR for indolent lymphoma or CLL without prior R for at least 6 months. A second treatment cycle given ≥6 months later after progression of disease (POD) was included. In contrast, in the absence of POD, subsequent courses of R maintenance to consolidate or maintain a prior response were excluded. Pts with previously transformed lymphoma were ≥five years from any aggressive lymphoma. The presence or absence of GELF criteria, FLIPI score, IPI score, Rai stage and NCI guidelines for the treatment of SLL/CLL was assessed.
Results: SAR was given 285 times in 240 pts. 92 (32%) were treatment naive. Histologies included follicular lymphomas (FL) grades 1 and 2 (n=107), FL grade 3 or not otherwise specified (n=31), SLL/CLL (n=59), marginal zone (=54) and other indolent lymphomas (n=34). The pts ranged in age from 22 to 90, with a median age of 66. IPI scores: low risk in 159 (56%); FLIPI scores: low risk in 66 (58%). Additionally, among SLL/CLL patients, 42 out of 59 (71%) were classified as having Rai Low Risk disease. At treatment initiation 167/285 (59%) met no GELF criteria. Within histologic subsets the prevalence of GELF treatment indications did not differ substantially with respect to prior therapy, although NCI treatment guidelines were more prevalent among treatment naive patients with SLL/CLL than in relapsed pts.
GELF and NCI Criteria by Histologic Subset and Prior Treatment Prior Prior RX No GELF GELF No NCI SLL/CLLIndication NCI SLL/CLLIndication FL (n=138) No (n=50) 31 (62%) 19 (38%) Yes (n=88) 52 (59%) 37 (41%) Non-FLL/SLL/CLL(n=88) No (n=43) 29 (67%) 14 (33%) Yes (n=45) 28 (62%) 17 (38%) SLL/CLL (n=59) No (n=30) 8 (27%) 22 (73%) 12 (40%) 18 (60%) Yes (n=29) 11 (38%) 18 (62%) 15 (52%) 14 (48%)
For the subset of SLL/CLL pts, the presence of newer, adverse prognostic factors was determined including high ZAP-70, high CD38+, and unmutated VH gene. VH gene mutation status was not evaluated in any patient before immunotherapy. CD38 levels were checked in 28/59: 19 high positive, 2 low positive, and 7 negative. ZAP-70 was evaluated in 13/59 cases: 6 high positive, 3 low positive, and 4 negative. Physicians often stated more than one indication for therapy. The most common stated impetus for treatment was progression (63%). The justification for therapy involved symptoms in 6% of cases, threatened end-organ function in 16%, cytopenias in 10%, bulky disease in 5%, patient preference in 4%, histologic transformation in 1%, and other reasoning in 19%.
Conclusions: At our institution, expert hematologists treating indolent lymphomas and CLL used criteria beyond GELF and NCI indications to justify therapy with SAR in more than half the patients receiving such therapy. This likely reflects the drug’s low toxicity and, possibly, a desire to spare patients from future chemotherapy. This finding has significant implications for resource allocation. Future studies may demonstrate whether relatively early use of SAR results in diminished chemotherapy usage over a patient’s lifetime.