Page 165 - Haematologica Vol. 109 - July 2024

ARTICLE - MAIC in 3L+ FL
M.J. Maurer et al.
included an anti-CD20-directed therapy and an alkylating agent. Seventy-three patients (17%) were excluded due to presence of variables that did not meet the inclusion / exclusion criteria based on the GO29781 clinical trial (On- line Supplementary Table S1), and 157 patients (36%) were excluded due to missing data on one or more variables from inclusion / exclusion criteria and inability to confirm all GO29781 eligibility criteria, yielding 211 patients for the application of the MAIC analysis. An additional 9 patients were missing one or more of the matching variables, result- ing in 202 LEO CReWE patients for the primary analysis. Full details on the 202 LEO CreWE patients prior to weighting can be found in Online Supplementary Table S2. The index therapy utilized in the primary analysis was 3rd line for 116 patients (57%), 4th line for 48 patients (24%), and 5th line or later for 38 patients (19%). Median age at index therapy was 60 years (IQR: 53-68), and 118 patients (58%) were male. Most patients (N=157, 78%) had stage III/IV disease at in- dex therapy; 59 patients (29%) had elevated LDH at index therapy and 31 (15%) had bulky disease (>7 cm). Eighty-six patients (43%) experienced POD24 following first-line IC, 63 patients (31%) had disease progression after 24 months to front-line IC, and 53 patients (26%) did not receive first- line IC. One hundred and twenty-three patients (61%) had received prior anthracycline, and 26 patients (13%) had re- ceived a prior autologous stem cell transplant. One hundred and forty-one patients (70%) had FL refractory to previous CD20 antibody therapy, with 38% refractory to alkylating agents, and 69% refractory to their most recent prior line of therapy. The median time from diagnosis to index line was 62 months (IQR 41-93), and the median time from start of prior therapy to start of index line was 11 months (IQR 4-15). The most common class of therapy at index line was CD20 antibody-based IC (N=57, 28%). Additional therapy class included novel therapies with or without CD20 anti- body (N=47, 23%), CD20 antibody and lenalidomide-based therapy (N=28, 14%), platinum-based salvage chemotherapy (N=23, 11%), and CD20 antibody monotherapy (N=18, 9%) (Online Supplementary Table S3). Twenty-eight patients (14%) received a stem cell transplant as index therapy (N=18 au- tologous and N=10 allogeneic), 7 received chimeric antigen receptor (CAR) T-cell therapy, and 4 received a bi-specific antibody; 80 patients (40%) received index therapy on a clinical trial (Online Supplementary Table S4). Most patients (N=171, 85%) received their index therapy at one of the eight LEO institutions. Response assessment on index therapy was positron emission tomography (PET)- or PET/computed tomography (CT)-based in 109 patients (54%), CT-based in 73 patients (36%), and clinical or unspecified in 20 patients (10%). At a median follow-up of 58.0 months from start of index therapy (range 0.03-252), 107 patients (53%) had had a PFS event after index therapy, and 47 patients (23%) had died. The unweighted CR and ORR in the 202 patients were 58% (95% CI: 51-65) and 78% (95% CI: 71-83), respectively; the unweighted 12-month PFS was 65% (95% CI: 59-72).
GO29781 trial
Details on the GO29781 trial have been previously reported.8 Most relevant to this analysis, median age at study entry in the 90 patients enrolled was 60 years (IQR 53-67), and 61% were male. LDH was elevated in 39% at study entry. Median number of previous lines of therapy was 3 (IQR 2-4), with 38% receiving 2 previous lines, 31% receiving 3 previous lines, and 31% receiving more than 3 previous lines. Thirty-eight patients (42%) had POD24 to front-line immunochemotherapy, and 48 (53%) had double-refractory disease to previous anti-CD20 and alkylator therapies.
Primary comparison of LEO CReWE to GO29781 by matching-adjusted indirect comparison weighted analysis
Prior to weighting, significant differences were observed in the clinical characteristics of the primary analysis cohort selected from the LEO CReWE (N=202) and the GO29781 trial (Table 1). LEO CReWE patients were less heavily pre-treat- ed and had fewer cases of double refractory disease. LEO CReWE patients also had a longer time from previous treatment to their index therapy. Application of the MAIC utilizing the 5 matching variables resulted in an effective sample size (ESS; the number of independent non-weight- ed individuals that would be required to give an estimate with the same precision as the weighted sample estimate) of 127.3 and a weighted N of 167; the distribution of the weights is shown in Online Supplementary Figure S1. MAIC weighting rebalanced the distributions of all 5 matching variables, including number of prior lines of therapy. Oth- er key clinical variables were also better aligned between the LEO CReWE and GO29781 studies after application of weights (Table 1). ORR observed in the weighted LEO CReWE cohort (73%, 95% CI: 65-80%) was lower than the ORR (80%, 95% CI: 70-88%) reported on the GO29781 trial (Table 2). Similarly, CR in the weighted LEO CReWE cohort (53%, 95% CI: 45-61%) was lower than the GO29781 trial (60%, 95% CI: 49-70%). PFS at 12 months was similar in the LEO CReWE cohort (12-month PFS 60%, 95% CI: 51- 69%) and the GO29781 trial (12-month PFS 58%, 95% CI: 47-68%) (Figure 2).
Sensitivity analyses
We performed a series of pre-specified sensitivity analyses to determine the impact of inclusion/exclusion criteria, matching variables, and index therapy selection on the outcomes in the study (Table 3). Application of GO29781- based trial criteria and the requirement of non-missing data in the LEO CReWE cohort resulted in exclusion of over half of potential patients (230 out of 441 potential patients, 52%) from the primary analysis. Utilizing an alternative set of clinical trial inclusion / exclusion criteria had little impact on sample size or study results compared to the primary analysis. Ignoring the clinical trial eligibility criteria would have greatly increased the overall (N=357) and ef-
Haematologica | 109 July 2024
2179