Radiotherapy in younger patients with advanced aggressive B-cell lymphoma-long-term results from the phase 3 R-MegaCHOEP trial.

The role of consolidative radiotherapy (RT) for patients with aggressive B-cell lymphoma has not been fully elucidated. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantations compared to conventional immunochemotherapy (R-CHOEP) for high-risk patients up to 60 years. The study protocol included RT for patients with bulky (maximum diameter ≥7.5 cm) or extranodal disease. Two-hundred sixty-one patients were analyzed, 120 of whom underwent RT. The most frequently irradiated regions were mediastinum (n = 50) and paraaortic (n = 27). Median RT dose was 36 Gray in median fractions of 1.8 Gray. Acute toxicities were mostly mild to moderate, with only 24 and 8 grade 3 and 4 toxicities reported during RT. Patients with bulky disease who received RT showed significantly better 10-year EFS, PFS and OS (EFS: 64% vs. 35%; p < 0.001; PFS 68% vs. 47%; p = 0.003; OS: 72% vs. 59%; p = 0.011). There was no significant increase in secondary malignancies with the use of RT. RT administered for consolidation of bulky disease after immunochemotherapy improved the prognosis of young high-risk patients with aggressive B-cell lymphoma and should be considered part of first-line therapy. The trial was registered with ClinicalTrials.gov, number NCT00129090.

Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma.

BACKGROUND AIMS: The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown. METHODS: In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively. RESULTS: The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders). CONCLUSIONS: For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.

Impact of TP53 Genomic Alterations in Large B-Cell Lymphoma Treated With CD19-Chimeric Antigen Receptor T-Cell Therapy.

PURPOSE: Tumor-intrinsic features may render large B-cell lymphoma (LBCL) insensitive to CD19-directed chimeric antigen receptor T cells (CAR-T). We hypothesized that TP53 genomic alterations are detrimental to response outcomes in LBCL treated with CD19-CAR-T. MATERIALS AND METHODS: Patients with LBCL treated with CD19-CAR-T were included. Targeted next-generation sequencing was performed on pre-CAR-T tumor samples in a subset of patients. Response and survival rates by histologic, cytogenetic, and molecular features were assessed. Within a cohort of newly diagnosed LBCL with genomic and transcriptomic profiling, we studied interactions between cellular pathways and TP53 status. RESULTS: We included 153 adults with relapsed or refractory LBCL treated with CD19-CAR-T (axicabtagene ciloleucel [50%], tisagenlecleucel [32%], and lisocabtagene maraleucel [18%]). Outcomes echoed pivotal trials: complete response (CR) rate 54%, median overall survival (OS) 21.1 months (95% CI, 14.8 to not reached), and progression-free survival 6 months (3.4 to 9.7). Histologic and cytogenetic LBCL features were not predictive of CR. In a subset of 82 patients with next-generation sequencing profiling, CR and OS rates were comparable with the unsequenced cohort. TP53 alterations (mutations and/or copy number alterations) were common (37%) and associated with inferior CR and OS rates in univariable and multivariable regression models; the 1-year OS in TP53-altered LBCL was 44% (95% CI, 29 to 67) versus 76% (65 to 89) in wild-type (P = .012). Transcriptomic profiling from a separate cohort of patients with newly diagnosed lymphoma (n = 562) demonstrated that TP53 alterations are associated with dysregulation of pathways related to CAR-T-cell cytotoxicity, including interferon and death receptor signaling pathway and reduced CD8 T-cell tumor infiltration. CONCLUSION: TP53 is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with LBCL treated with CD19-CAR-T. The role of TP53 should be further validated in independent cohorts.

Superior outcomes with paediatric protocols in adolescents and young adults with aggressive B-cell non-Hodgkin lymphoma.

Survival disparities by locus of care (LOC; paediatric versus adult) among adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) are well documented. Whether similar disparities exist among AYA with aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is unknown. We identified all Ontario, Canada AYA aged 15-21 years at diagnosis of B-NHL between 1992 and 2012. Demographic, disease, treatment and outcome data were chart abstracted. The impact of LOC on event-free (EFS) and overall survival (OS) were determined, adjusted for patient and disease covariates. Among 176 AYA with B-NHL, 62 (35·2%) received therapy at paediatric centres. The 5-year EFS and OS [± standard error (SE)] for the overall cohort were 72·2 [3·4]% and 76·1 [3·2]% respectively. Both EFS and OS were superior among paediatric centre AYA [EFS (± SE) 82·2 (4·9)% vs. 66·7 (4·4)%, P = 0·02; OS 85·5 (4·5)% vs. 71·1 (4·3)%, P = 0·03]. Adjusted for histology, stage and time period, adult centre AYA had inferior EFS [hazard ratio (HR) 2·4, 95% confidence interval (CI) 1·1-4·9, P = 0·02] and OS (HR 2·5, 95% CI 1·1-5·7, P = 0·03). Sensitivity analyses restricted to the latest time period, when most adult centre AYA received rituximab, demonstrated similar disparities. Similar to AYA with ALL, AYA with B-NHL may benefit from being treated with paediatric protocols. Studies prospectively validating these results are warranted.

End of treatment FDG-PET in primary mediastinal B-cell lymphoma treated with R-chemotherapy: Prognostic indicator and implications for consolidation radiotherapy.

The ideal therapeutic regimen in primary mediastinal B-cell lymphoma (PMBCL) is controversial and may include consolidation radiotherapy (RT). An adequate strategy is essential in a population where long-term effects of RT are significant. We evaluated the prognostic value of end-of-treatment (EOT) FDG-PET in 50 patients receiving rituximab and anthracycline-containing chemotherapy and its implications for consolidative RT. Thirty patients (60%) obtained complete metabolic response (CMR), five received consolidation RT. The remaining patients had partial response (14) and progression (6). Of these, 12 received mediastinal RT, six salvage chemotherapy, and two no further treatment. Five-year progression free survival was 100% and 48% (95% CI 30%-77%) in patients with negative and positive EOT FDG-PET, respectively (P < .001). Five-year overall survival for negative and positive EOT FDG-PET was 100% and 67% (95% CI 48%-93%) respectively (P = .001). Within positive EOT FDG-PET cases, an association was found between Deauville score and survival. The negative predictive value (NPV) of EOT FDG-PET for disease relapse/progression was 100% (95% CI 0.88-1.00); the positive predictive value was 47% (95% CI 0.24-0.71). This study demonstrates the importance of metabolic assessment in PMBCL and is relevant for its high NPV. Our data favor the use of EOT FDG-PET for decisions concerning RT.

Prognostic Significance of Cytokine Release Syndrome in B Cell Hematological Malignancies Patients After Chimeric Antigen Receptor T Cell Therapy.

Cytokine release syndrome (CRS) is the most common on-target toxicity of chimeric antigen receptor (CAR) T cell therapy. However, the prognostic significance of CRS has not been well elucidated. The aim of our study was to evaluate the association between CRS and efficacy after anti-CD19 CAR-T therapy in a retrospective cohort of 22 patients with relapsed/refractory B cell hematological malignancies. The complete remission (CR) rates after CAR-T therapy were 68%, and median value for progression-free survival (PFS) was 6.8 months. Eight of 22 (36.4%) patients showed ≥ grade 2 CRS. Statistical analysis found that patients with ≥ grade 2 CRS had higher CR rates and longer PFS than those with < grade 2 CRS. Moreover, bridging hematopoietic stem cell transplantation was another independent predictor for PFS. These data suggested that appropriate CRS may be beneficial to the efficacy of CAR-T therapy. The Clinical Trial Registration number is NCT03110640, NCT03302403.

The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis.

Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0-163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34+ cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.

Novel Biological Insights and New Developments in Management of Burkitt Lymphoma and High-Grade B-Cell Lymphoma.

OPINION STATEMENT: Burkitt lymphoma (BL) is highly curable, and prompt institution of therapy is critical to achieving optimal outcomes. Although current "standard" approaches are very effective in disease eradication, treatment-related toxicity makes optimal delivery of curative therapy a challenge, especially in older and immunocompromised individuals. Reduced intensity approaches with fewer toxic complications have been the focus of some recent studies. A critical question is if they can replace "standard" approaches by maintaining high curability with improved tolerability. Additionally, new molecular insights in BL biology suggest that in the future, "targeted therapy" approaches may be feasible using small molecule inhibitors and novel strategies. Recently, a new category of aggressive lymphoma named "high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 translocations" has been recognized. This category overlaps clinically and biologically with BL and has an inferior prognosis compared to most B-cell lymphomas, and the optimal approach to its management remains, as yet, undefined. In this review, we discuss the current landscape of BL treatment including recent results with low-intensity regimens and also consider current approaches to HGBL. We also explore how recently elucidated novel biological insights in BL biology may shape future therapeutic directions including the use of novel cellular therapy approaches.

The value of complete remission according to positron emission tomography prior to autologous stem cell transplantation in lymphoma: a population-based study showing improved outcome.

BACKGROUND: Chimeric antigen-receptor T-cell and bispecific antibody therapies will likely necessitate a reconsideration of the role of autologous stem-cell transplantation (ASCT) in lymphoma. Patients who are likely to profit from ASCT need to be better identified. METHODS: Here, we investigated the value of positron emission tomography/computerized tomography (PET/CT) before ASCT. All 521 patients transplanted for lymphoma 1994-2019 at Karolinska (497 conditioned with BEAM) were included. RESULTS: Outcome improved over three calendar periods 1994-2004, 2005-2014, 2015-2019 (2-year overall survival [OS]: 66, 73, 83%; P = 0.018). Non-relapse mortality (NRM) at 100 days over the three periods were 9.8, 3.9, 2.9%, respectively. The OS improvement between 1994 and 2004 and 2005-2014 was due to lower NRM (P = 0.027), but the large OS advance from 2015 was not accompanied by a significant reduction in NRM (P = 0.6). The fraction of PET/CT as pre-ASCT assessment also increased over time: 1994-2004, 2%; 2005-2014, 24%; 2015-2019, 60% (P < 0.00005). Complete responses (PET/CT-CR) were observed in 77% and metabolically active partial responses (PET/CT-PR) in 23%. PET/CT-CR was a predictor for survival in the entire population (P = 0.0003), also in the subpopulations of aggressive B-cell (P = 0.004) and peripheral T-cell (P = 0.024) lymphomas. Two-year OS and progression-free survival (OS/PFS) for patients in PET/CT-CR were in relapsed/refractory aggressive B-cell lymphoma 87%/75% and peripheral T-cell lymphoma 91%/78%. The corresponding figures in PET/CT-PR were 43%/44 and 33%/33%. Patients with solitary PET/CT-positive lesions showed acceptable outcome with ASCT followed by local irradiation (2-year OS/PFS 80%/60%). CT was less discriminative: 2-year OS/PFS: CT-CR, 76%/66%; CT-PR, 62%/51%. Outcome was inferior after BEAC compared with BEAM conditioning. CONCLUSIONS: We conclude that the improved outcome reflects better, PET/CT-informed, identification of patients who should proceed to ASCT. The excellent survival of patients in PET/CT-CR indicates that ASCT should remain part of standard therapy for lymphoma.

Perspectives on outpatient administration of CAR-T cell therapy in aggressive B-cell lymphoma and acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T-cell therapies that specifically target the CD19 antigen have emerged as a highly effective treatment option in patients with refractory B-cell hematological malignancies. Safety and efficacy outcomes from the pivotal prospective clinical trials of axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel and the retrospective, postmarketing, real-world analyses have confirmed high response rates and durable remissions in patients who had failed multiple lines of therapy and had no meaningful treatment options. Although initially administered in the inpatient setting, there has been a growing interest in delivering CAR-T cell therapy in the outpatient setting; however, this has not been adopted as standard clinical practice for multiple reasons, including logistic and reimbursement issues. CAR-T cell therapy requires a multidisciplinary approach and coordination, particularly if given in an outpatient setting. The ability to monitor patients closely is necessary and proper protocols must be established to respond to clinical changes to ensure efficient, effective and rapid evaluation either in the clinic or emergency department for management decisions regarding fever, sepsis, cytokine release syndrome and neurological events, specifically immune effector cell-associated neurotoxicity syndrome. This review presents the authors' institutional experience with the preparation and delivery of outpatient CD19-directed CAR-T cell therapy.

Clinical characteristics of patients with B-cell lymphoma enrolled in clinical trials for aggressive lymphoma in Japan: Japan Clinical Oncology Group - Lymphoma Study Group study - JCOG0108A.

The clinical characteristics of B-cell lymphoma (BCL) were studied through the combined analysis of six clinical trials conducted by the Japan Clinical Oncology Group - Lymphoma Study Group (JCOG-LSG) for aggressive lymphoma in the 1990s, before the introduction of rituximab. Through a central pathological review, 829 patients were diagnosed with BCL according to the World Health Organization classification and treated with doxorubicin-containing combination chemotherapies. Of these patients, 642, 104, 30, and 24 patients were diagnosed with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL), respectively. The overall survival (OS) of FL and MZL patients was higher than that of patients with DLBCL and MCL. The OS of the MCL patients was higher than that of DLBCL patients in the first 5 years, but MCL had the lowest survival after 5 years. The OS of DLBCL patients was clearly stratified by the international prognostic index and showed data compatible with that of aggressive lymphoma in the pre-rituximab era. These results established the clinical aspects of BCL in a large number of patients treated in prospective studies during the pre-rituximab era in Japan.

The standardized uptake value calculated from 111In-ibritumomab tiuxetan single-photon emission computed tomography/computed tomography is a useful predictor of the clinical response in patients treated by 90Y- ibritumomab tiuxetan therapy.

90Y-Ibritumomab tiuxetan (IT) therapy is a radioimmunotherapy for indolent B-cell lymphoma. Several predictors of insufficient therapeutic effects have been reported. We performed a retrospective study at a single institute to investigate whether 111In SPECT/CT can predict the therapeutic effects and grade of cytopenia due to 90Y-IT therapy. We enrolled 16 consecutive patients who underwent 90Y-IT therapy, including 15 who underwent 111In-IT SPECT/CT. After 90Y-IT therapy, there were 4 patients in complete remission in whom the lesion SUVmax on 111In-IT SPECT/CT and soluble IL-2 receptor were significantly lower than those of the other patients (P<0.05 and P<0.05, respectively). Based on the log-rank test of factors associated with the progression-free survival (PFS), ≥2 previous treatment regimens was significantly associated with a poor prognosis (P<0.05). The SUV on 111In-IT SPECT/CT may be a good predictor of the clinical response to 90Y-IT therapy.

Real-life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B-cell lymphomas.

Transplant-ineligible relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) patients represent an unmet medical need. Polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADG), with bendamustine- rituximab(BR) has recently gained approval for these patients, both in the USA and Europe, based on the GO29365 phase IIb trial. Real-life data with Pola are extremely limited. We report the outcomes of 61 Greek patients, who received Pola-(B)R mainly within a compassionate use program. Treatment was given for up to six 21-day cycles. Bendamustine was omitted in three cases due to previous short-lived responses. Fourty-nine rrDLBCL(efficacy cohort-EC) and 58 rr aggressive B-NHL (safety cohort-SC) patients received at least 1 Pola-BR cycle. Twenty-one (43%) patients of the EC responded with 12/49 (25%) CR and 9/49 (18%) PR as best response. Median progression-free survival, overall survival and duration of response were 4.0, 8.5, and 8.5 months respectively, while 55% of patients experienced a grade ≥3 adverse event, mainly hematologic. Treatment discontinuations and death during treatment were mainly due to disease progression. Twenty-two (41%) patients received further treatment; 11/22 are still alive, including one after CAR-T cells, and two after stem cell transplantation. Our data confirm that Pola-BR is a promising treatment for rrDLBCL patients, inducing an adequate response rate with acceptable toxicity. Pola-BR could be used as bridging therapy before further consolidative treatments.

Targeting miR-21 with NL101 blocks c-Myc/Mxd1 loop and inhibits the growth of B cell lymphoma.

Background: NL101 has shown activities against multiple myeloma and acute myeloid leukemia, but its anti-lymphoma activity remains unknown. The transcription factor c-Myc is frequently dysregulated in aggressive B cell lymphomas such as double-hit lymphoma, for which the standard of care is still lacking. A novel approach to target c-Myc needs to be explored. Although the role of oncogenic microRNA-21 (miR-21) was well established in an inducible mice model of B cell lymphoma, whether targeting miR-21 could inhibit the growth of B cell lymphoma and its underlying mechanisms is unclear. Methods: We used MTT assay and flow cytometry to determine the inhibitory effect of NL101 on the cell proliferation of B cell lymphoma in vitro. The lymphoma xenograft mice models were generated to evaluate the anti-lymphoma function in vivo. Western blot and qPCR were applied to measure the expression levels of protein and microRNA, respectively. To investigate the mechanisms of action in NL101, we used genechip to profile differentially-expressed genes upon NL101 induction. Luciferase reporter system and chromatin immunoprecipitation were used for the validation of target gene or miRNA. Results: Nl101 significantly inhibited B cell lymphoma proliferation through induction of cell cycle arrest and apoptosis. NL101 suppressed the growth of B cell lymphoma in vivo and prolonged the survival of lymphoma xenograft models. Gene expression profiling revealed that miR-21 was significantly decreased upon the induction of NL101 in B cell lymphoma. The miR-21 level was associated with the sensitivity of NL101. miR-21 inhibited Mxd1 expression via directly combining to Mxd1 3'-UTR; c-Myc activated miR-21 expression by directly binding to the miR-21 promoter. Conclusion: NL101 significantly inhibited the growth of B cell lymphoma in vitro and in vivo. The novel c-Myc/miR-21/Mxd1 positive-feedback loop is critical for the maintenance of B cell lymphoma survival. Targeting miR-21 to block c-Myc/miR-21/Mxd1 loop represents a novel potential strategy of c-Myc-directed therapy.

Attenuated cytarabine, etoposide, dexamethasone plus rituximab (R-Mini-CYVE) regimen for patients with relapsed or refractory B-cell non-Hodgkin's lymphoma not eligible for intensive chemotherapy.

OBJECTIVES: To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R-mini-CYVE) in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). METHODS: We included pretreated adult patients with B-cell NHL who were ineligible for high-dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty. Up to 8 cycles were administered. RESULTS: Between 2013 and 2019, 56 patients with diffuse large B-cell lymphoma (n = 45, 80%) and indolent B-cell lymphoma (n = 11, 20%) were included. Median age was 75 (range: 36-88). Nineteen patients (35%) had a performance status ≥2. Patients received a median of 4 cycles of R-mini-CYVE. The objective response and the complete response rates were 50% and 33%, respectively. Median progression-free survival and overall survival times were 5.7 (95% CI: 0.5-10.9) and 14.7 (95% CI: 3.5-25.9) months, respectively. Grade ≥3 anaemia, thrombocytopenia and neutropenia occurred in 44%, 55% and 60% of the patients, respectively. The most frequent non-haematological grade ≥3 adverse events were sepsis (21%), fatigue (13%) and cytarabine-related neurotoxicity (5%). CONCLUSION: R-mini-CYVE demonstrated a meaningful antitumour efficacy and an acceptable safety profile in patients with relapsed/refractory B-cell NHL who were ineligible for HDT.

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis.

INTRODUCTION: Polatuzumab vedotin is approved therapy in the United States for relapsed/refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab (Pola+BR). However, the safety and efficacy of Pola+BR outside of a clinical trial setting is unknown. PATIENTS AND METHODS: We analyzed use of pola-based therapy at 5 centers in the United States, including dose, response rates, progression-free survival (PFS), survival, and toxicity. RESULTS: Sixty-nine patients with aggressive B-cell lymphoma, including 66 with diffuse large B-cell lymphoma/high-grade B-cell lymphoma and 84% refractory to prior therapy, were treated. Responses occurred in of 50%, including 24% complete response. Median duration of response was 5.1 months, PFS was 2.0 months, and survival was 5.3 months, at 4 months median follow-up. Inferior PFS was associated with prior refractory disease (median, 57 days vs. not reached; P = .003) and lack of response to Pola+BR (PFS, 27 days vs. 152 days; P < .001). Discontinuation owing to planned cellular therapy was seen in 36% and owing to toxicity occurred in 12%; unplanned hospitalizations occurred in 36%. CONCLUSIONS: We conclude that commercial Pola is applied to highly refractory lymphomas at our centers, often with intent to bridge to subsequent therapy. Although some clinical benefit was observed, efficacy was inferior to clinical trial data, especially among those with refractory disease.