Publications

Treatment patterns and outcomes post-CAR T failure in LBCL: the "what comes next" question

Flatiron Health — Wed, 04 Nov 2026 14:00:06 GMT

Overview

While chimeric antigen receptor T-cell (CAR T) therapy has advanced care for relapsed or refractory large B-cell lymphoma (LBCL), over half of patients eventually experience disease relapse. This real-world study evaluated demographics, treatment patterns, and outcomes among 815 patients in the US Flatiron Health Research Database with LBCL who initiated a subsequent line of therapy following CAR T failure.

The most common post-CAR T treatment classes were chemoimmunotherapy (26.6%) and bispecific antibodies (20.1%). Treatment patterns reflected an era shift: chemoimmunotherapy was predominant in earlier years (35.1%), whereas bispecific antibodies became the most common salvage choice in the modern era across both second-line (39.3%) and third-line or later (30.5%) settings. Overall median real-world progression-free survival was 3.8 months and median real-world overall survival was 9.8 months. Outcomes varied by relapse timing, with late relapses (>6 months post-CAR T) exhibiting longer real-world overall survival (21.4 months) compared to primary refractory disease (6.8 months) or early relapses (11.3 months).

Real-world comparison of biologic features, treatment patterns, and clinical outcomes between younger (≤55 years) and older (>55 years) patients with CLL receiving frontline targeted therapy

Flatiron Health — Wed, 04 Nov 2026 14:00:05 GMT

Overview

Patients aged ≤55 years represent a small minority of individuals with chronic lymphocytic leukemia (CLL). This study compared biological features, frontline treatment patterns, and real-world outcomes between younger (≤55 years, n=520) and older (>55 years, n=6,294) patients initiating first-line BTK inhibitor or BCL2 inhibitor therapy in the US Flatiron Health Research Database between 2019 and 2026.

Younger patients presented with higher Rai stages (44.5% vs 31.2% stage II–IV), higher Black representation (15% vs 8.2%), and higher rates of unmutated IGHV (59% vs 54%) and del(11q) (21% vs 17%), but lower rates of TP53 mutation (8.1% vs 17%) and del(17p) (8.5% vs 12%) among patients with available testing. On multivariable analysis, younger age was independently associated with longer time to next treatment (5-year rate: 52% vs 43%) and longer overall survival (5-year rate: 92% vs 69%).

When MRD matters: clinical interpretation and treatment decision-making after measurable residual disease testing in multiple myeloma

Flatiron Health — Wed, 04 Nov 2026 14:00:05 GMT

Overview

Measurable residual disease (MRD) testing detects small amounts of cancer remaining after treatment and is increasingly used to assess treatment response in multiple myeloma, a cancer of plasma cells. However, less is known about how clinicians interpret MRD results and use them to guide treatment decisions.

Using electronic health record data from the Flatiron Health Research Database, researchers analyzed 5,686 MRD tests from 2,442 patients. A large language model (LLM)-enabled approach was used to examine clinical notes and characterize physicians' interpretations, treatment rationale, and subsequent management decisions.

The proportion of tests using molecular methods increased from 14% in 2015–2019 to 52% in 2025 or later. MRD was identified as a primary driver of treatment decisions in approximately 25% of evaluable assessments, but more commonly served as supporting information rather than the deciding factor.

Within 90 days of MRD testing, treatment escalation, including consolidation, occurred following 38% of assessments, while treatment discontinuation occurred following 6%. Escalation was more common after positive MRD results, whereas discontinuation was more common after negative results. However, these treatment changes were not necessarily driven by MRD findings.

Association of lymphopenia with outcomes in diffuse large B cell lymphoma in the era of T-cell directed therapies

Flatiron Health — Wed, 04 Nov 2026 14:00:03 GMT

Overview

Absolute lymphocyte count (ALC) is a marker of immune status, but its prognostic role in diffuse large B-cell lymphoma (DLBCL) in the era of T-cell-directed therapies remains understudied. This retrospective study evaluated 8,777 adults with DLBCL in the US Flatiron Health Research Database to assess associations between lymphopenia (ALC < 1.0 × 10^9/L) and clinical outcomes.

At diagnosis, 34.3% of patients had lymphopenia. Baseline lymphopenia was independently associated with poorer outcomes, including shorter median real-world overall survival (82 vs 101 months) and shorter time to next treatment (26 vs 63 months). Patients with baseline lymphopenia were also more likely to eventually receive T-cell-directed therapy. Among 559 patients who received CAR T or bispecific antibody therapy, severe pre-treatment lymphopenia (ALC < 0.5 × 10^9/L measured within 90 days prior to therapy) was independently associated with shorter overall survival (median 13.6 vs 54 months).

Frontline treatment and consolidation strategies and associated outcomes in primary central nervous system lymphoma: a large US real-world study

Flatiron Health — Wed, 04 Nov 2026 14:00:03 GMT

Overview

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive subtype of extranodal B-cell lymphoma with no standardized care pathway. This study characterized clinical characteristics, treatment patterns, and outcomes among 2,792 patients diagnosed with PCNSL in the US Flatiron Health Research Database, comprising over 82,000 patients with large B-cell lymphoma, between 2011 and 2026.

High-dose methotrexate (HD-MTX)-based regimens were the predominant first-line induction approach, received by 41% of patients as HD-MTX ± rituximab. Documented consolidation was infrequent overall (15% radiation, 9.4% stem cell transplant [HCT], 7.9% high-dose cytarabine). Median real-world progression-free survival and overall survival were 25.4 months and 60.5 months, respectively. Intensive induction and consolidative HCT were associated with longer survival outcomes, though these strategies were more commonly utilized among younger patients and within academic medical centers.

Treatment patterns across lines of therapy among patients with newly diagnosed multiple myeloma in the United States

Flatiron Health — Wed, 04 Nov 2026 14:00:02 GMT

Overview

The treatment landscape for newly diagnosed multiple myeloma (NDMM) has evolved rapidly with the introduction of anti-CD38 monoclonal antibodies (aCD38), but contemporary treatment patterns remain poorly understood. This longitudinal study evaluated treatment patterns, temporal trends, and patient drop-off across lines of therapy among 7,364 patients with MM in the US Flatiron Health Research Database initiating first-line (1L) therapy between 2020 and 2025.

By 2025, 1L aCD38-containing regimen use reached 94.7%, up from 13.3% in 2020, among stem cell transplant (SCT) recipients and 78.0%, up from 10.6% in 2020, among non-SCT recipients. In subsequent settings, aCD38-containing regimens remained common, received by 69.1% of patients in second-line and 54.2% in third-line care between 2020 and 2026. T-cell-redirecting therapies (CAR T and bispecific antibodies) were used infrequently until later lines (up to 32.9% in fifth-line care). Substantial attrition occurred between lines, with over half of patients failing to advance to a subsequent line.

Real-world treatment patterns of novel immune-based therapy utilization in relapsed/refractory multiple myeloma: evidence from a contemporary cross-sectional analysis

Flatiron Health — Wed, 04 Nov 2026 14:00:02 GMT

Overview

Recent guideline updates supporting the use of BCMA- and GPRC5D-directed (novel) therapies in earlier lines of therapy have expanded treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, real-world uptake of novel therapies following these updates remains poorly understood. This cross-sectional study evaluated contemporary real-world treatment patterns among 1,936 patients initiating a new line of therapy for RRMM in the US Flatiron Health Research Database between January 2025 and April 2026.

Non-BCMA/GPRC5D doublet and triplet regimens remained the primary therapies across lines, accounting for 77% of treatments in second/third line (2L/3L), 69% in fourth line (4L), and 53% in fifth line or higher (5L+). Utilization of novel BCMA- or GPRC5D-directed therapies was 8% in 2L/3L and reached 24% in 4L, with higher uptake in academic (34% in 4L) compared to community settings (16% in 4L). Patient numbers decreased significantly across successive lines (1,016 in 2L vs 357 in 4L).

The CAR-T funnel: AI-assisted mapping of patient attrition and barriers across the second-line CAR-T pathway in relapsed/refractory diffuse large B-cell lymphoma

Flatiron Health — Wed, 04 Nov 2026 14:00:01 GMT

Overview

Although second-line (2L) CAR T-cell therapy is approved for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), real-world uptake remains limited. This retrospective study used an LLM to extract documented discussions and reasons for non-receipt across the 2L CAR T care pathway for 577 patients in the US Flatiron Health Research Database who experienced first-line treatment failure.

While 62.7% of patients had a documented CAR T discussion, sequential drop-off occurred along the care pathway: 49.4% were referred, 39.0% underwent evaluation, 23.2% completed apheresis, and 20.6% received CAR T infusion in 2L. Among non-infused patients with a documented discussion, primary barriers to receipt included comorbidities (22.4%), patient preference (19.1%), poor performance status (17.8%), rapid disease progression (14.5%), and financial considerations (9.9%).

Real-world safety and effectiveness of elranatamab in multiple myeloma, including in late-line and BCMA-exposed patients

Flatiron Health — Wed, 04 Nov 2026 14:00:01 GMT

Overview

Elranatamab, a BCMA-directed bispecific antibody, requires step-up dosing (SUD) to mitigate cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This retrospective study evaluated real-world outcomes and safety across care settings among 119 triple-class exposed patients with relapsed/refractory multiple myeloma in the Flatiron Health Research Database.

Most patients initiated step-up dosing in the inpatient setting (71%), while 16% received step-up dosing in the outpatient setting. Patients had a median of 5 prior lines of therapy (38% prior BCMA-exposed). Median real-world overall survival was 19.1 months and median progression-free survival was 12.4 months. CRS and ICANS incidence were 31% and 14% overall, respectively, and were predominantly Grade 1–2 with similar rates across inpatient and outpatient settings. No CRS, ICANS, or infection events resulted in treatment discontinuation or death.

Real-world treatment patterns and outcomes over time of patients with high-grade B-cell lymphoma in a large US oncology network

Flatiron Health — Wed, 04 Nov 2026 14:00:01 GMT

Overview

High-grade B-cell lymphoma (HGBCL) is an aggressive malignancy with no established standard frontline or salvage regimen. This study used the US Flatiron Health Research Database, comprising over 82,000 patients with large B-cell lymphoma, to describe real-world treatment trends and survival among 3,964 patients diagnosed across two time periods: Early-era (2016–2021, n=2,199) and Late-era (2022–2026, n=1,765).

Frontline therapy selection remained consistent across eras, most commonly R-CHOP (~29%) and R-EPOCH variants (~35%). In second-line and subsequent settings, treatment patterns shifted away from hematopoietic cell transplantation (5.1% in Early-era vs 1.4% in Late-era) toward CAR T therapy (7.1% vs 14%) and bispecific antibodies (1.0% vs 11%). In descriptive Kaplan-Meier analyses, median 1L real-world overall survival (51.1 months overall) and progression-free survival (20.1 months overall) appeared similar between eras.