Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Corrigendum: Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

Clinical Outcomes of Patients with Multiple Myeloma after Daratumumab Failure.

Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments.

Impact of SCHOLAR-1 Criteria on Chimeric Antigen Receptor T Cell Therapy Efficacy in Aggressive B Lymphoma: A Real-World GELTAMO/GETH Study.

In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real-world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we analyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diagnosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable disease as the best response to ≥4 cycles of first-line therapy or ≥2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognostic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non-SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era.

Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease.

PURPOSE: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. METHODS: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio-MRD method with PET/CT in detecting MRD at follow-up. RESULTS: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio-MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio-MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). CONCLUSION: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance.

Low-risk HPLLs/ABC score patients with splenic marginal zone lymphoma can be safely managed without treatment: Results from a prospective Spanish study.

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.

Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.

Role of allogeneic hematopoietic cell transplant for relapsed/refractory aggressive B-cell lymphomas in the CART era.

Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. In the multivariate analysis, CART was confirmed to be similar to alloHCT for the primary study endpoint (progression-free survival) (hazard ratio [HR] 0.92, CI95%:0.56-1.51, p = 0.75). Furthermore, when the analysis was limited to only patients with chemo-sensitive diseases (complete and partial response) at infusion (CART = 26, alloHCT=93), no differences were reported (progression-free survival at month +18: 65% versus 55%, p = 0.59). However, CART had lower non-relapse mortality (HR 0.34, 95% CI: 0.13-0.85, p = 0.02). Given the lower toxicity and similar survival outcomes, these results suggest the use of CART before alloHCT.

Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT.

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we used an ultra-deep sequencing approach with 2 · 10-4 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients. Positive LiqBio-MRD at first-line therapy correlated with a higher risk of progression both at the interim evaluation (HRINT 11.0, 95% CI 2.10-57.7, p = 0.005) and at the end of treatment (HREOT, HR 19.1, 95% CI 4.10-89.4, p < 0.001). Similar results were observed by PET/CT Deauville score, with a median PFS of 19 months vs. NR (p < 0.001) at the interim and 13 months vs. NR (p < 0.001) at EOT. LiqBio-MRD and PET/CT combined identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future response-adapted clinical trials.

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP).

INTRODUCTION: Belantamab mafodotin (BM) is a new anti-BCMA antibody-drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). METHODS: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Thirty-three patients were included with a median of 70 years of age (range, 46-79 years). Median time from diagnosis was 71 months (range, 10-858 months). Median prior lines was 5 (range, 3-8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1-16 doses), with a median follow-up of 11 months (6-15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92-5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10-0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107-740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). CONCLUSIONS: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study.

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.

Safety and tolerability of a 90-minute rapid infusion of Sandoz biosimilar rituximab in B-cell lymphoproliferative disorders in a real-world setting.

Although rituximab is generally well-tolerated, infusion-related reactions (IRRs) are common with the initial dose when administered intravenously according to standard recommendations. To prevent IRRs, premedication and low-speed infusion rates have been recommended. Consequently, intravenous (i.v.) infusion of rituximab can become a labor-intensive process. Rapid i.v. rituximab infusion over 90 min has demonstrated a favorable safety profile for the second and subsequent infusions during the course of therapy. The aim of this study was to investigate the safety and tolerability of 90-min rapid infusion of Sandoz rituximab biosimilar (SDZ-RTX) for patients with CD20+ lymphoma or chronic lymphocytic leukemia (CLL). We retrospectively reviewed all patients with CD20+ lymphoma or CLL who received SDZ-RTX infusions in 90 min from July 2019 to July 2021 at seven Spanish hospitals. The primary end point was the incidence of IRRs. We identified 124 patients and 576 rapid administrations of SDZ-RTX, with an average of five rapid infusions per patient. Most rapid infusions of SDZ-RTX were in combination with CHOP/CHOP-like therapy (48.4%), followed by SDZ-RTX alone (15.1%), in combination with bendamustine (14.5%), or with other regimens (22%). The 90-min SDZ-RTX infusion schedule was well-tolerated with no grade 3/4 IRRs. The incidence of any grade IRR during the first rapid infusion was 1% (5 grade 1 IRRs and 1 grade 2 IRR). In conclusion, rapid 90-min i.v. administration of SDZ-RTX for the second and subsequent infusions during the course of therapy is well-tolerated in patients with CD20+ lymphoma or CLL.

Early progression in follicular lymphoma in the absence of histological transformation or high-risk Follicular Lymphoma International Prognostic Index still has a favourable outcome.

Although follicular lymphoma (FL) patients relapsing within 24 months after first-line treatment (POD24) have a poor prognosis, some cases show notable survival after first relapse (SF1R). We aimed to characterize the POD24 FL population and to identify the main prognostic factors at progression. We selected 162 POD24 patients (80F; median age at first relapse 59 years) from a cohort of 1067 grades 1-3a FL-treated patients. The remaining 905 patients treated with first-line immunochemotherapy and diagnosed during the same period were used to compare outcomes in terms of survival. After a median follow-up of 11.0 years, 96 patients died (10y-SF1R of 40%). Age over 60 years (p < 0.001), high lactate dehydrogenase (LDH) (p < 0.001), haemoglobin (Hb) less than 120 g/L (p < 0.001), advanced stage (p < 0.001), high-risk Follicular Lymphoma International Prognostic Index (FLIPI) (p < 0.001), histological transformation (HT) (p < 0.001) and reaching less than complete response (CR) after salvage therapy (p < 0.001), predicted poor SF1R at relapse. In multivariate analysis only high-risk FLIPI and HT maintained prognostic significance for SF1R. POD24 patients not transformed and with low/intermediate FLIPI at relapse behaved better than the remaining cases. POD24 patients showed an excess mortality of 38% compared to the general population. Although outcome of POD24 FL patients is poor, a considerable group of them (low/intermediate FLIPI and not transformed at first relapse) behave better.

Corrigendum: Personalized monitoring of circulating tumor DNA with a specific signature of trackable mutations after chimeric antigen receptor T-cell therapy in follicular lymphoma patients.

[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

Usability Evaluation of a Noninvasive Neutropenia Screening Device (PointCheck) for Patients Undergoing Cancer Chemotherapy: Mixed Methods Observational Study.

BACKGROUND: Patients with cancer undergoing cytotoxic chemotherapy face an elevated risk of developing serious infection as a consequence of their treatment, which lowers their white blood cell count and, more specifically, their absolute neutrophil count. This condition is known as neutropenia. Neutropenia accompanied by a fever is referred to as febrile neutropenia, a common side effect of chemotherapy with a high mortality rate. The timely detection of severe neutropenia (<500 absolute neutrophil count/µL) is critical in detecting and managing febrile neutropenia. Current methods rely on blood draws, which limit them to clinical settings and do not allow frequent or portable monitoring. In this study, we demonstrated the usability of PointCheck, a noninvasive device for neutropenia screening, in a simulated home environment without clinical supervision. PointCheck automatically performs microscopy through the skin of the finger to image the blood flowing through superficial microcapillaries and enables the remote monitoring of neutropenia status, without requiring venipuncture. OBJECTIVE: This study aimed to evaluate the usability of PointCheck, a noninvasive optical technology for screening severe neutropenia, with the goal of identifying potential user interface, functionality, and design issues from the perspective of untrained users. METHODS: We conducted a multicenter study using quantitative and qualitative approaches to evaluate the usability of PointCheck across 154 untrained participants. We used a mixed method approach to gather usability data through user testing observations, a short-answer qualitative questionnaire, and a standardized quantitative System Usability Scale (SUS) survey to assess perceived usability and satisfaction. RESULTS: Of the 154 participants, we found that 108 (70.1%) scored above 80.8 on the SUS across all sites, with a mean SUS score of 86.1 across all sites. Furthermore, the SUS results indicated that, out of the 151 users who completed the SUS survey, 145 (96%) found that they learned how to use PointCheck very quickly, and 141 (93.4%) felt very confident when using the device. CONCLUSIONS: We have shown that PointCheck, a novel technology for noninvasive, home-based neutropenia detection, can be safely and effectively operated by first-time users. In a simulated home environment, these users found it easy to use, with a mean SUS score of 86.1, indicating an excellent perception of usability and placing this device within the top tenth percentile of systems evaluated for usability by the SUS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04448314; https://clinicaltrials.gov/ct2/show/NCT04448314 (Hospital Universitario 12 de Octubre registration) and NCT04448301; https://clinicaltrials.gov/ct2/show/NCT04448301 (Boston Medical Center registration).

Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma.

The ELARA trial indicates tisagenlecleucel (tisa-cel) is an effective anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory follicular lymphoma (r/r FL). As ELARA is a single-arm trial, this study compares tisa-cel outcomes from the ELARA trial with usual care from a real-world cohort. ELARA enrolled 98 patients as of 29 March 2021 (median follow-up: 15 months from enrollment). Usual care data were obtained from ReCORD-FL, a global retrospective study of patients with r/r FL, who met similar eligibility criteria to ELARA. With a data cutoff date of 31 December 2020, 187 patients with ≥2 preceding treatment lines were included in the ReCORD-FL (median follow-up: 57 months from third-line) study. An indirect treatment comparison was performed for 97 patients from the ELARA trial and 143 patients from the ReCORD-FL study with no missing data on baseline factors. The line of therapy for which outcomes were assessed was selected or matched between cohorts using propensity score modeling. After baseline factor adjustment via weighting by odds, complete response rate (CRR; 95% confidence interval) was 69.1% (59.8%-78.3%) for tisa-cel vs. 37.3% (26.4%-48.3%) for usual care; overall response rate was 85.6% (78.7%-92.5%) vs. 63.6% (52.5%-74.7%). Kaplan-Meier probability of being progression/event-free at 12 months was 70.5% (61.4%-79.7%) for tisa-cel vs. 51.9% (40.6%-63.3%) for usual care, with hazard ratio (HR)=0.60 (0.34-0.86); 12-month overall survival was 96.6% (92.9%-100%) vs. 71.7% (61.2%-82.2%), with HR=0.2 (0.02-0.38). In conclusion, tisa-cel was associated with a 1.9-fold higher complete response rate and a 1.4-fold higher rate of being progression or event free at 12 months vs usual care, as well as a death risk reduction of 80%. The findings provide additional evidence on the benefit of tisa-cel in patients with r/r FL after ≥2 treatment lines. This trial was registered at www.clinicaltrials.gov as NCT03568461.