High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study.

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.

Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions.

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes.

Patient Characteristics and Outcomes of Outpatient Tisagenlecleucel Recipients for B Cell Non-Hodgkin Lymphoma.

Tisagenlecleucel (tisa-cel) is an approved CD19-directed chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory B cell malignancies. Given potentially life-threatening toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, inpatient tisa-cel infusion and toxicity monitoring are often considered; however, the toxicity profile of tisa-cel may be conducive to outpatient administration. Here we review the characteristics and outcomes of tisa-cel recipients treated in the outpatient setting. Patients age ≥18 years with B cell non-Hodgkin lymphoma who received tisa-cel between June 25, 2018, and January 22, 2021, at 9 US academic medical centers were included in a retrospective analysis. Six of the 9 representative centers (75%) had an outpatient program in place. A total of 157 patients were evaluable, including 93 (57%) in the outpatient treatment group and 64 (43%) in the inpatient treatment group. Baseline characteristics, toxicity and efficacy, and resource utilization were summarized. The most common lymphodepletion (LD) regimen was bendamustine in the outpatient group (65%) and fludarabine/cyclophosphamide (91%) in the inpatient group. The outpatient group had more patients with a Charlson Comorbidity Index of 0 (51% versus 15%; P < .001), fewer patients with an elevated lactate dehydrogenase (LDH) level above the normal range at the time of LD (32% versus 57%, P = .003) compared to the inpatient group, and a lower Endothelial Activation and Stress Index score (.57 versus 1.4; P < .001). Any-grade CRS and ICANS were lower in the outpatient group (29% versus 56% [P < .001] and 10% versus 16% [P = .051], respectively). Forty-two outpatient tisa-cel recipients (45%) required an unplanned admission, with a median length of stay of 5 days (range, 1 to 27 days), compared to 13 days (range, 4 to 38 days) in the inpatient group. The median number of tocilizumab doses administered was similar in the 2 groups as were the rate of intensive care unit (ICU) transfer (5% versus 8%; P = .5) and median length of ICU stay (6 days versus 5 days; P = .7). There were no toxicity-related deaths in the 30 days post-CAR-T infusion in either group. Progression-free survival and overall survival were similar in the 2 groups. With careful patient selection, outpatient tisa-cel administration is feasible and associated with similar efficacy outcomes as inpatient treatment. Outpatient toxicity monitoring and management may help optimize healthcare resource utilization.

Sarcopenia Predicts Inferior Progression-Free Survival in Lymphoma Patients Treated with Autologous Hematopoietic Stem Cell Transplantation.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival for patients with chemotherapy-sensitive lymphoma. Validated scoring systems are used in the clinical setting to predict treatment toxicity and survival; however, complications related to disease and treatment still occur, highlighting challenges in optimal patient selection and the need for novel predictors. Analysis of body composition and muscle mass can provide an objective assessment to identify vulnerable populations, as sarcopenia and frailty have been reported to predict outcomes in other tumor types. In this retrospective cohort study of patients undergoing ASCT for lymphoma, we investigated associations of sarcopenia with clinically significant outcomes, including overall survival (OS) and progression-free survival (PFS). Computed tomography (CT) images of 78 patients obtained routinely pretransplantation were used to assess skeletal muscle mass and are reported as skeletal muscle index (SMI). OS, PFS, and clinical outcomes of interest were compared between groups. Twenty-seven patients (34.6%) in the cohort met the criteria for sarcopenia. Patients with sarcopenia had a significantly shorter 3-year PFS (59% [95% confidence interval (CI), 38% to 75%] versus 84% [95% CI, 71% to 92%]; P = .02) after 3 years of follow up, whereas there was no difference in OS between patients with and those without sarcopenia (78% [95% CI, 57% to 89%] versus 88% [95% CI, 76% to 95%]; P = .25). Interestingly, no difference in survival was found with stratification based on the Karnofsky Performance Scale or Hematopoietic Cell Transplantation-Specific Comorbidity Index. There also were no significant between-group differences in length of hospital stay and the incidences of other clinical outcomes of interest, including febrile neutropenia, mucositis, total parenteral nutrition requirement, acute kidney injury, rate of readmission, or intensive care unit admission. This is the first study to our knowledge to correlate sarcopenia with disease control and PFS after ASCT in lymphoma. Possible explanations include a higher rate of chemotherapy-related toxicity, leading to disruptions of treatment as well as dysfunction of antitumor immunity secondary to impaired regulations from myokines from the loss of muscle mass or an unknown cause that is yet to be elucidated. Physical therapy programs and personalized regimens for treatment based on the analysis of body composition indices can be further studied and implemented to mitigate treatment-related toxicity and to optimize survival in patients with sarcopenia.

Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival.

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [CI]: 2.9-6.0). None developed extra-pulmonary disease. Part 3: 5-year survival: 94% (95% CI: 84%-98%) for LCH-SSL, 78% (95% CI: 59%-90%) for LCH-MSL, and 75% (95% CI: 53%-89%) for LCH-MSNL. LCH patients presenting with isolated pulmonary signs or symptoms rarely have extra-pulmonary involvement at the time of diagnosis and generally do not develop extra-pulmonary progression. LCH-SSL has the best overall survival, while LCH-MSL and LCH-MSNL have similar clinical outcomes.