Management of Canadian Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) in the Real-World

Background: Nearly 35-40% of pts with DLBCL have R/R disease after first-line (1L) treatment (tx). Recommended 2L tx is salvage chemotherapy with or without autologous stem cell transplant (ASCT) in eligible pts. Pts who fail to respond to salvage therapy or are ASCT-ineligible have poor prognosis. Few tx have been recently approved for R/R DLBCL, including CD19 chimeric antigen receptor T-cell (CAR-T) therapy, polatuzumab vedotin plus bendamustine and rituximab (POLA-BR), and tafasitamab plus lenalidomide (TAFA+LEN). Understanding currently used regimens may help identify optimal tx options for R/R DLBCL.

RE-MIND2 (NCT04697160; Nowakowski et al. CCR. 2022) was designed to capture pt-level data for pts with R/R DLBCL to match the L-MIND study (NCT02399085) of TAFA+LEN, creating a synthetic control arm to this single-arm registration trial. As real-world data (RWD) on management of pts with R/R DLBCL are very limited in Canada, the purpose of this descriptive, post hoc subanalysis was to better understand the disease landscape, real-world pt characteristics, and current management of Canadian pts enrolled in the RE-MIND2 study.

Methods: Two major Canadian academic centers (Cross Cancer Institute, AB; Hôpital Maisonneuve Rosemont, QC) participated in RE-MIND2. Data were retrospectively collected on pts diagnosed between 2010 and 2020 from health records. Eligible pts were ≥18 y with histologically confirmed DLBCL, who had received ≥2 systemic therapies (including ≥1 anti-CD20 therapy) administered according to NCCN/ESMO guidelines. Descriptive statistics were used to analyze baseline characteristics, tx initiated, and duration of tx by line of therapy.

Results: Data from 109 Canadian R/R DLBCL pts who met RE-MIND2 study criteria, out of 118 screened, were included in this analysis. Pts were grouped by eligibility criteria met for therapy line (2L: 97 [89.0%], 3L: 41 [37.6%], 4L: 17 [15.6%]). Pt demographics and disease characteristics are shown in Table 1. Age at index date ranged from 26-86 y; 76 pts (69.7%) were men. At initial diagnosis, 52 pts (47.7%) had germinal center B-cell (GCB) DLBCL, 31 (28.4%) had non-GCB, and 26 (23.9%) had missing data; 20 (18.3%) had transformed DLBCL. One pt had triple-hit and 6 had double-hit lymphoma, representing ~6% of this cohort.

Sixty-four pts (58.7%) had primary refractory DLBCL due to primary progressive disease while on their 1L of tx (33 [30.3%]) or early relapse ≤6 mo following the end of their 1L of tx (31 [28.4%]). The number of pts eligible for ASCT at the start of current tx line were 2L: 72 (74.2%), 3L: 7 (17.1%), 4L: 1 (5.9%). Of those ASCT-ineligible (2L: 24 [24.7%], 3L: 34 [82.9%], 4L: 16 [94.1%]), most common reasons were chemorefractoriness (2L: 9 [37.5%], 3L: 18 [52.9%], 4L: 9 [56.3%]) and advanced age (2L: 10 [41.7%], 3L: 6 [17.6%], 4L: 2 [12.5%]).

Most commonly prescribed (>10%) tx were 2L-ASCT (45.4%) and gemcitabine plus dexamethasone, cisplatin, and rituximab (R±GDP; 32.0%) mostly used as salvage therapy but without proceeding to transplant; 3L-Others (39.0%), CAR-T (24.4%), and rituximab plus ifosfamide, carboplatin, and etoposide (R±ICE; 9.8%); 4L-Others (29.4%), CAR-T (29.4%), and bendamustine (17.6%) (Table 2). In 2L, of the 72 ASCT-eligible pts, 29 (~40%) did not proceed to transplantation and received available systemic therapies. In 3L, "Others" were most frequently used therapies (47.1%) in ASCT-ineligible pts. CAR-T therapy was second most common (26.5%) in this cohort, likely owing to commercial access available from 2019 in Canada. Four of the 15 pts who received a CAR-T therapy were infused through clinical trials. Median duration of tx exposure for pts not receiving ASCT ranged from 0.43-3.48 mo in 2L, 0.49-2.0 in 3L, and 0.03-1.41 in 4L (Table 2).

Conclusion: Understanding country-specific patterns of care and outcomes is important for planning future studies and clinical decisions. Tx patterns in Canadian pts with R/R DLBCL demonstrate that although ASCT is the 2L standard of care (SoC) for eligible pts, there is no SoC in ASCT-ineligible pts or in those who do not receive a transplant. Following 1L tx, different approved therapies were used for 2L and beyond. RWD acquired before approval of the latest agents suggests there is a need for novel, safe, and effective therapeutic options to improve duration of tx and outcomes for pts with R/R DLBCL. Further retrospective DLBCL Canadian registry analyses are needed to confirm these findings.

Peters:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nowakowski:Bantam Pharmaceutical: Consultancy; Blueprint Medicines Corporation: Consultancy; Celgene Corporation/Bristol Myers Squibb: Consultancy, Research Funding; Curis, Inc.: Consultancy; Daiichi Sankyo Inc: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Genentech, Inc: Consultancy, Research Funding; Incyte: Consultancy; Karyopharm: Consultancy; Kite Pharma Inc.: Consultancy; Kymera Therapeutics: Consultancy; MorphoSys US Inc: Consultancy; NanoString: Research Funding; Ryvu Therapeutics: Consultancy; Selvita: Consultancy; TG Therapeutics: Consultancy; Zai Lab: Consultancy. Dabas:Incyte: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Amoloja:Incyte: Current Employment, Current equity holder in publicly-traded company. Xue:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Koch:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Waltl:MorphoSys: Current Employment. Fleury:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Grant during the conduct of the study , Research Funding, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.