Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study

Abstract

The SCHOLAR-5 study examines treatment patterns and outcomes of real-world follicular lymphoma (FL) patients on 3rd line of treatment (LoT) or higher, for whom existing data are limited. SCHOLAR-5 is a retrospective cohort study using data from adults (≥ 18 years) with grade 1-3a FL, initiating ≥3rd LoT after June 2014 at major lymphoma centers in the US and Europe. Objective response rate (ORR), complete response (CR), progression-free survival (PFS) and overall survival (OS) were analyzed by LoT. Time-to-event outcomes were assessed using Kaplan-Meier methods. Of 128 patients, 87 initiated 3rd LoT, 63 initiated 4th LoT, and 47 initiated 5th LoT. At 1st eligible LoT, 31% progressed within 24-months of 1st LoT anti-CD20 combination therapy, 28% had prior autologous stem cell transplantation, and 31% were refractory to the previous LoT. The most common regimen in each LoT was chemoimmunotherapy; however, experimental drugs were increasingly used at later LoT. In the US, anti-CD20 monotherapy was more common at ≥3rd LoT compared to Europe, where stem cell transplants were more common. ORR at 3rd LoT was 68% (CR 44%), but decreased after each LoT to 37% (CR 22%) in ≥5 LoT. Median OS and PFS at 3rd LoT were 68 and 11 months, respectively, and reduced to 43 and 4 months at ≥5 LoT. Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved CR in later LoT, and duration of response and survival diminished with each subsequent line.

Figure 1.

Flowchart of patient selection at Memorial Sloan Ket-tering Cancer Center. ^†Eligibility criteria were patients aged ≥18 years; with histologically confirmed diagnosis of indolent non-Hodgkin lymphoma (iNHL), with histological subtype limited to follicular lymphoma (FL) grade 1, grade 2, or grade 3a based on criteria established by the World Health Organization 2016 classification; with relapsed/refractory (r/r) disease (i.e., r/r iNHL). Patients with transfomed FL, FL histological grade 3b, prior anti-CD19 CAR T-cell therapy or other genetically modified T-cell therapy were excluded. Patient were only included if eligible within 12 months before the last updated version of the sites database.

Figure 2.

Flowchart of patient and line-of-therapy exclusion by continent. Sixty patients contributed multiple lines of therapy (LoT) to the analysis set, with these patients contributing a median of 2 LoT (range, 2-6). FL: follicular lymphoma. MZL: marginal zone lymphoma.

Figure 3.

Treatment paterns. Experimental category does not include recently accepted treatments (PI3K-δ inhibitors, R, and EZH2i), even if they were not approved at the time of the study. (A) Treatments received by eligible patients, by line of therapy (LoT). The percentage values represent the proportion of patients who contribute to each LoT. (B) Eligible 3^rd LoT by continent. (C) Eligible 4^th LoT by continent. Note that (A) includes treatments received prior to the approval of idelalisib, whereas (B and C) include only treatments received after 23^rd July 2014. Benda: bendamustine; CD20: anti-CD20 monoclonal antibodies; Chemo: chemotherapy; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP: cyclophosphamide, vincristine, prednisolone; EZH2i: enhancer of zeste homolog 2 specific inhibitors, ImiDs: immunomodulatory drugs; R: rituximab and lenalidomide; SCT: stem cell transplant; PI3Ki: phosphoinositide 3-kinase inhibitor.

Figure 4.

Survival curves by line of therapy. (A) Overall survival and (B) progression-free survival by line of therapy (LoT). Blue: 3^rd LoT; green: 4^th LoT; yellow: 5^th LoT; red: 6^th LoT. (C) Time to next treatment.