Autologous hematopoietic cell transplantation consolidation for first response is associated with longer survival among patients with nodal peripheral T-cell lymphoma.

BACKGROUND: Nodal peripheral T-cell lymphomas (PTCLs) are challenging subsets of non-Hodgkin lymphomas characterized by their heterogeneity and aggressive clinical behavior. Given the mixed outcomes reported in previous studies, the efficacy of autologous hematopoietic cell transplantation (auto-SCT) as a consolidation strategy following initial chemotherapy response remains uncertain. OBJECTIVE: This study aims to evaluate the impact of upfront auto-SCT consolidation on overall survival (OS) and event-free survival (EFS) among patients with nodal PTCL who achieved a complete or partial response to initial chemotherapy. STUDY DESIGN: A retrospective cohort study was conducted at Moffitt Cancer Center, involving 123 patients with nodal PTCL treated between February 2005 and February 2021. Patients were stratified into two groups based on whether they received auto-SCT as part of their initial treatment strategy. Kaplan-Meier method and Cox proportional hazard models were used for statistical analysis to compare OS and EFS between groups. RESULTS: Patients undergoing auto-SCT after first response demonstrated significantly longer median OS (12.3 vs. 4.3 years; P = .035) and EFS (6.2 vs. 2.2 years; P = .003) compared to those who did not. Multivariate analyses indicated that auto-SCT at first response and younger age at diagnosis were favorable prognostic factors. CONCLUSION: The findings suggest that upfront auto-SCT consolidation can significantly improve long-term outcomes in patients with nodal PTCL, supporting the strategy of early auto-SCT consideration and referral following initial chemotherapy response. These results underscore the importance of integrating upfront auto-SCT into the treatment paradigm for nodal PTCL, emphasizing early referral to transplantation services to optimize patient outcomes.

Quality of life in the digital age: young adult hematopoietic stem cell transplantation patients and healthcare providers' views of telehealth.

PURPOSE: The COVID-19 pandemic shifted the healthcare field from in-person clinic visits to virtual-based telehealth appointments. This study explored young adult (YA) hematopoietic stem cell transplantation (HSCT) patient and physician communication preferences and quality of life. METHODS: One researcher conducted semi-structured interviews with n = 10 YA HSCT patients and n = 10 healthcare providers (HPs). HPs included physicians (n = 5) and advanced practice provider (APP) (nurse practitioners and physician assistants) (n = 5). Interviews lasted approximately 10-15 min, were held over Zoom®, and were audio-recorded. Interviews were professionally transcribed verbatim, and two independent researchers conducted a thematic analysis using Dedoose®. RESULTS: Common themes included the following: (1) convenience, (2) improved communication, (3) technology issues, and (4) quality of life for patients and physicians. In general, most patients (n = 7; 70%) preferred in-person visits over telehealth for initial appointments, stating they chose the "social connection" and "engagement" associated with in-person visits. For "check-ins" and follow-up appointments (n = 5; 50%), patients preferred hybrid appointments. Physicians (n = 4; 80%) preferred telehealth stating it was "convenient," "timesaving," and improved "compliance." In contrast, all APP staff (n = 5; 100%) preferred in-person visits, stating in-person improved "relationships" with patients and was more "convenient" than using electronic devices for telehealth. CONCLUSION: Providers differed in preference. APP personnel preferred in-person visits and HSCT physicians preferred telehealth appointments. YA HSCT patients preferred in-person for initial appointments and hybrid clinic visits for follow-up appointments.

Hypomethylating Agents and Venetoclax for Acute Myeloid Leukemia Relapsed After Hematopoietic Stem Cell Transplant.

BACKGROUND: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment. PATIENTS AND METHODS: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi. RESULTS: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle. CONCLUSION: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity.

A US Multicenter Collaborative Study on Outcomes of Hematopoietic Cell Transplantation in Hepatosplenic T-Cell Lymphoma.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients. Fifty-three patients with HSTCL were included in the study. Thirty-six patients received an allo-HCT and 17 received an auto-HCT. Thirty-five (66%) were males. Median age at diagnosis was 38 (range 2 to 64) years. Median follow-up for survivors was 75 months (range 8 to 204). The median number of prior lines of therapy was 1 (range 1 to 4). Median OS and progression-free survival (PFS) for the entire cohort were 78.5 months (95% CI: 25 to 79) and 54 months (95% CI: 18 to 75), respectively. There were no significant differences in OS (HR: 0.63, 95% CI: 0.28 to 1.45, P = .245) or PFS (HR: 0.7, 95% CI: 0.32 to 1.57, P = .365) between the allo-HCT and auto-HCT groups, respectively. In the allo-HCT group, the 3-year cumulative incidence of relapse was 35% (95% CI: 21 to 57), while 3-year cumulative incidence of NRM was 16% (95% CI: 7 to 35). In the auto-HCT group, the 3-year cumulative incidence of relapse and NRM were 43% (95% CI: 23 to 78) and 14% (95% CI: 4 to 52), respectively. Both Auto-HCT and Allo-HCT are effective consolidative strategies in patients with HSTCL, and patients should be promptly referred for HCT evaluation.

New Approaches for the Treatment of AML beyond the 7+3 Regimen: Current Concepts and New Approaches.

Fifty years have passed since the development of the first chemotherapy regimen for treating acute myelogenous leukemia (AML), with the approval in 1973 of the cytarabine daunorubicin (7+3) regimen. Until recently, patients diagnosed with AML had very limited treatment options and depended primarily on chemotherapy in combinations, doses, or schedules of the same drugs. Patients with advanced age, comorbidities, or relapsed or refractory disease were left with no effective options for treatment. New advances in the understanding of the biology and the molecular and genetic changes associated with leukemogenesis, as well as recent advances in drug development, have resulted in the introduction over the last few years of novel therapeutic agents and approaches to the treatment of AML as well as a new classification of the disease. In this article, we will discuss the new classification of AML; the mechanisms, actions, and indications of the new targeted therapies; the chemotherapy combinations; and the potential role of cellular therapies as new treatment options for this terrible disease.

Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.

A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy. SIGNIFICANCE: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.

Sirolimus Is an Acceptable Alternative to Tacrolimus for Graft-versus-Host Disease Prophylaxis after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.

Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor HCT. A phase II study from the Moffitt Cancer Center substituting sirolimus (Siro) for Tac in this prophylactic regimen reported comparable rates of grade II-IV acute GVHD (aGVHD). Many centers have substituted Siro for Tac in this setting based on a preferable side effect profile, although comparative data are limited. In this study, we retrospectively compared outcomes in haplo-HCT with PTCy/Siro/MMF versus haplo-HCT with PTCy/Tac/MMF. The study cohort included all consecutive patients receiving haploidentical donor T cell-replete peripheral blood stem cell (PBSC) HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. A total of 423 patients were included, of whom 84 (20%) received PTCy/Siro/MMF and 339 (80%) received PTCy/Tac/MMF. The median age for the entire cohort was 54 years (range, 18 to 78 years), and the median follow-up was 30 months. The Siro group had a higher proportion of patients age ≥60 years (58% versus 34%; P < .01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV aGVHD (45% versus 47%; P = .6) at day +100 or chronic GVHD (cGVHD) (47% versus 54%; P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better in the Tac group (odds ratio, .30; 95% confidence interval, .1 to .83; P = .02), with a median time to engraftment of 17 days versus 18 days in the Siro group, but platelet engraftment was similar in the 2 groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on aGVHD or cGVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease-free survival, or overall survival after PBSC haplo-HCT. These findings suggest that Siro is a comparable alternative to Tac in combination with PTCy/MMF for GVHD prophylaxis, with overall similar clinical outcomes despite delayed engraftment after peripheral blood stem cell haplo-HCT. Although Tac remains the standard of care, Siro may be substituted based on the side effect profile of these medications, with consideration of patient medical comorbidities at HCT.

Nutritional status and body mass index before hematopoietic stem cell transplantation (HSCT) and associated outcomes: a rapid review.

PURPOSE: Hematopoietic stem cell transplantation (HSCT) recipients experience several post-HSCT complications affecting nutritional status, body mass index (BMI), and mortality that can potentially be mitigated by nutritional management. This rapid review examines the relationship between pre-HSCT nutritional status and BMI and post-HSCT survival. METHODS: Articles were identified from PubMed, Scopus, and Embase. Two researchers independently completed the title, abstract, and full-text review. Inclusion criteria included the following: (1) randomized clinical trials or observational studies; (2) human subjects diagnosed with cancer and undergoing HSCT; (3) reported pre-HSCT nutritional status (e.g., diet recall, nutritional survey, dietitian session) or BMI; and (4) reported treatment related mortality and/or survival. RESULTS: The initial search found 3036 articles, 28 were included in full-text review, and 18 met inclusion criteria. Articles had quasi-experimental (n = 2) and observational (n = 16) study designs. Of the studies, n = 5 reported nutritional intake decreased post-HSCT, and n = 2 reported nutrition intervention (i.e., controlled feeding) post-HSCT improved survival. Four studies reported having a BMI classified as underweight improved survival, while n = 5 reported having a BMI classified as overweight or obese improved survival. CONCLUSION: Current research exploring the relationship between nutritional status and BMI with HSCT survival is mixed. Further research is needed to determine how nutritional status and BMI are associated withsurvival post-HSCT to inform future intervention work.

Feasibility and Toxicity of Full-Body Volumetric Modulated Arc Therapy Technique for High-Dose Total Body Irradiation.

Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CAR-T) approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Currently, the incidence of cardiac events associated with ide-cel remains unclear. This was a retrospective single-center observational study of patients treated with ide-cel for RRMM. We included all consecutive patients who received standard-of-care ide-cel treatment at least 1-month follow-up. Baseline clinical risk factors, safety profile, and responses were examined based on the development of a cardiac event. A total of 78 patients were treated with ide-cel, and 11 patients (14.1%) developed cardiac events: heart failure (5.1%), atrial fibrillation (10.3%), nonsustained ventricular tachycardia (3.8%), and cardiovascular death (1.3%). Only 11 of the 78 patients had repeat echocardiogram. Baseline risk factors associated with the development of cardiac events included being female sex and having poor performance status, λ light-chain disease, and advanced Revised International Staging System stage. Baseline cardiac characteristics were not associated with cardiac events. During index hospitalization after CAR-T, higher-grade (≥grade 2) cytokine release syndrome (CRS) and immune cell-associated neurologic syndrome were associated with cardiac events. In multivariable analyses, the hazard ratio for the association of the presence of cardiac events with overall survival (OS) was 2.66 and progression-free survival (PFS) was 1.98. Ide-cel CAR-T for RRMM was associated with similar cardiac events as other types of CAR-T. Worse baseline performance status and higher-grade CRS and neurotoxicity were associated with cardiac events after BCMA-directed CAR-T-cell therapy. Our results suggest that the presence of cardiac events may confer worse PFS or OS; although because of the small sample size, the power to detect an association was limited.

Belumosudil Impacts Immunosuppression Pharmacokinetics in Patients with Chronic Graft-versus-Host Disease.

Belumosudil (BEL) is a novel Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor approved for the treatment of chronic graft-versus-host disease (cGVHD) in patients who have failed 2 or more prior lines of systemic therapy. Although the pharmacokinetic effects of BEL on other immunosuppressive (IS) agents have not been clinically evaluated, in vitro data indicate that BEL may have possible interactions with drugs with a narrow therapeutic index used to treat cGVHD, such as tacrolimus, sirolimus, and cyclosporine, through cytochrome P450 (CYP3A) and p-glycoprotein interactions. Further evaluation of these potential interactions is warranted to optimize the safety and effectiveness of these medications when combined with BEL. In this study, we investigated the potential effects of BEL on sirolimus and tacrolimus levels when used concurrently by assessing changes in IS levels after the addition of BEL. This retrospective single-center study of patients who started BEL while on tacrolimus and/or sirolimus between February 1, 2019, to February 1, 2023, included patients who had IS levels measured at baseline prior to starting BEL and at least 1 subsequent IS measurement to assess changes over time. The primary endpoint was the concentration-dose (C/D) ratio analyzed before and after the addition of BEL. Secondary endpoints included the incidence of IS levels outside of the therapeutic range (subtherapeutic or supratherapeutic) and mean dosage changes over time. Thirty-seven patients met our eligibility criteria and were included in this analysis. Patients taking sirolimus (n = 30) or tacrolimus (n = 16) concurrently with BEL had a statistically significant increase in the C/D ratio (sirolimus recipients, 160% [P < .001]; tacrolimus recipients, 113% [P = .013]) between the pre-BEL and final post-BEL assessments. The C/D ratios for both tacrolimus and sirolimus recipients continued to increase at several time points after initiation of BEL, indicating that multiple drug dosage adjustments may be required. After BEL initiation, 19% of tacrolimus levels and 57% of sirolimus levels were supratherapeutic. Despite dosage adjustments, 27% of tacrolimus levels were supratherapeutic at both the second and third assessments after starting BEL, and 28% and 30% of sirolimus levels were supratherapeutic at these 2 time points, respectively. All 12 of the patients who discontinued BEL during the study period (100%) showed a return to their baseline C/D ratio, confirming that the C/D ratio change can be attributed to BEL. The impact of BEL on IS levels is clinically significant, warranting dosage adjustments of concurrent medications. A significant number of patients taking sirolimus with BEL had levels >15 ng/mL during the study period, indicating a potential risk for toxicity if this interaction is unmonitored. We recommend empiric dose reductions of 25% for tacrolimus and 25% to 50% for sirolimus when adding BEL, as well as close monitoring of IS levels during the initial weeks of BEL therapy. Future studies are warranted to better describe the impact of BEL on patients taking CYP3A inhibitors.

Cardiac and inflammatory biomarker differences in adverse cardiac events after chimeric antigen receptor T-Cell therapy: an exploratory study.

BACKGROUND: Chimeric antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough treatment for various hematological malignancies. However, cardiotoxicities such as new-onset heart failure, arrhythmia, acute coronary syndrome and cardiovascular death occur in 10-15% of patients treated with CAR-T. This study aims to investigate the changes in cardiac and inflammatory biomarkers in CAR-T therapy to determine the role of pro-inflammatory cytokines. METHODS: In this observational study, ninety consecutive patients treated with CAR-T underwent baseline cardiac investigation with electrocardiogram (ECG), transthoracic echocardiogram (TTE), troponin-I, and B-type natriuretic peptide (BNP). Follow-up ECG, troponin-I and BNP were obtained five days post- CAR-T. In a subset of patients (N = 53), serum inflammatory cytokines interleukin (IL)-2, IL-6, IL-15, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and angiopoietin 1 & 2 were tested serially, including baseline and daily during hospitalization. Adverse cardiac events were defined as new-onset cardiomyopathy/heart failure, acute coronary syndrome, arrhythmia and cardiovascular death. RESULTS: Eleven patients (12%) had adverse cardiac events (one with new-onset cardiomyopathy and ten with new-onset atrial fibrillation). Adverse cardiac events appear to have occurred among patients with advanced age (77 vs. 66 years; p = 0.002), higher baseline creatinine (0.9 vs. 0.7 mg/dL; 0.007) and higher left atrial volume index (23.9 vs. 16.9mL/m2; p = 0.042). Day 5 BNP levels (125 vs. 63pg/mL; p = 0.019), but not troponin-I, were higher in patients with adverse cardiac events, compared to those without. The maximum levels of IL-6 (3855.0 vs. 254.0 pg/mL; p = 0.021), IFN-γ (474.0 vs. 48.8pg/mL; p = 0.006) and IL-15 (70.2 vs. 39.2pg/mL; p = 0.026) were also higher in the adverse cardiac events group. However, cardiac and inflammatory biomarker levels were not associated with cardiac events. Patients who developed cardiac events did not exhibit worse survival compared to patients without cardiac events (Log-rank p = 0.200). CONCLUSION: Adverse cardiac events, predominantly atrial fibrillation, occur commonly after CAR-T (12%). The changes in serial inflammatory cytokine after CAR-T in the setting of adverse cardiac events suggests pro-inflammation as a pathophysiology and require further investigation for their role in adverse cardiac events. TWEET BRIEF HANDLE: CAR-T related Cardiotoxicity has elevated cardiac and inflammatory biomarkers. #CARTCell #CardioOnc #CardioImmunology.

Outcomes of CD19-Directed Chimeric Antigen Receptor T Cell Therapy for Transformed Nonfollicular Lymphoma.

CD19-directed chimeric antigen receptor (CAR) T cell (CAR-T) therapy with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) are approved for the treatment of relapsed or refractory large B cell lymphoma (LBCL), including de novo diffuse LBCL (DLBCL), primary mediastinal B cell lymphoma (PMBCL), and transformed follicular lymphoma (tFL). Transformed nonfollicular lymphomas (tNFLs), including transformed marginal zone lymphoma (tMZL) and transformed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) were not included in their respective pivotal studies. This study was conducted to evaluate the outcomes of axi-cel and tisa-cel in tNFL patients, including those who received ibrutinib concomitantly through apheresis, lymphodepletion, and CAR-T infusion. This single-center retrospective study included all patients with tCLL/SLL, tMZL, tFL, and DLBCL/PMBCL treated with CAR-T therapy outside of a clinical trial setting from November 2017 to May 2021 at Moffitt Cancer Center, Tampa, Florida. We analyzed and compared outcomes in patients with tCLL/SLL or tMZL and patients with DLBCL/tFL. The study included 134 patients who received a total of 136 CAR-T treatments (111 with axi-cel and 25 with tisa-cel). Ninety patients had de novo DLBCL/PMBCL, 23 had tFL, and 21 had tNFL (12 with tMZL and 9 with tCLL/SLL). The overall response and complete response rates were 66.7% and 55.6%, respectively, for tCLL/SLL and 92.9% and 71.4% for tMZL. The overall response and complete response rates were not different between tNFL and DLBCL/tFL (P = .92 and .81, respectively). At a median follow-up of 21.3 months, the median progression-free survival (PFS) for tCLL/SLL was 5.4 months (95% confidence interval [CI], .8 month to not assessable [NA]); for tMZL, the median PFS was not reached (NR) (95% CI, 2.3 months to NA); and for DLBCL/tFL, the median PFS was 14.3 months (95% CI, 5.6 months to NA) (P = .58). The estimated 1-year PFS rate was 29.6% (95% CI, 5.2% to 60.7%) for tCLL/SLL, 50.0% (95% CI, 22.9% to 72.2%) for tMZL, 42.7% (95% CI, 22.4% to 61.6%) for tNFL, and 53.0% (95% CI, 42.3% to 62.5%) for DLBCL/tFL. The median overall survival was NR (95% CI, 9.2 months to NA) for tCLL/SLL, 27.1 months (95% CI, 8.5 months to NA) for tMZL, and NR (95% CI, 17.4 months to NA) for DLBCL/tFL (P = .79). Compared to the DLBCL/tFL cohort, tNFL patients were more likely to develop immune effector cell-associated neurologic syndrome (ICANS) and to receive tocilizumab (P = .04 and .01, respectively, after controlling for CAR-T product) and with a possibly higher incidence of grade ≥3 cytokine release syndrome (CRS) (P = .07). Two patients in the tNFL cohort died of treatment-related toxicity after receiving axi-cel. Six tNFL patients received ibrutinib concurrently with tisa-cel, with 1 case of grade ≥3 CRS/ICANS that rapidly resolved and no other severe toxicities. Our case series supports the use of CD19 CAR-T therapy in relapsed/refractory tCLL/SLL and tMZL. The concurrent use of ibrutinib and tisa-cel in tNFL was associated with manageable toxicity in tNFL.

Three-Year Outcomes in Recipients of Mismatched Unrelated Bone Marrow Donor Transplants Using Post-Transplantation Cyclophosphamide: Follow-Up from a National Marrow Donor Program-Sponsored Prospective Clinical Trial.

The use of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has resulted in reductions in GVHD and improved outcomes in allogeneic hematopoietic cell transplantation (HCT) using HLA-mismatched related donors. We report the 3-year outcomes of the first multicenter prospective clinical trial using PTCy in the setting of mismatched unrelated donor (MMUD) bone marrow HCT. The study enrolled 80 patients, treated with either myeloablative conditioning (MAC; n = 40) or reduced-intensity conditioning (RIC; n = 40), with the primary endpoint of 1-year overall survival (OS). The median follow-up for this study was 34 months (range, 12 to 46 months) in the RIC group and 36 months (range, 18 to 49 months) in the MAC group. Three-year OS and nonrelapse mortality were 70% and 15%, respectively, in the RIC group and 62% and 10% in the MAC group. No GVHD was reported after 1 year. The incidence of relapse was 29% in the RIC group and 51% in the MAC group. OS did not differ based on HLA match grade (63% in the 7/8 strata and 71% in the 4 to 6/8 strata). These encouraging outcomes, which were sustained for 3 years post-HCT, support the continued exploration of MMUD HCT using a PTCy platform. Important future areas to address include relapse reduction and furthering our understanding of optimal donor selection based on HLA and non-HLA factors.

Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis.

Patients with renal impairment (RI) are typically excluded from trials evaluating chimeric antigen receptor (CAR) T cell therapies. We evaluated the outcomes of patients with RI receiving standard of care (SOC) CAR T cell therapy for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this retrospective, single-center cohort study of patients with R/R DLBCL treated with SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) after 2 or more prior lines of therapy, renal and survival outcomes were compared based on RI and fludarabine dose reduction (DR) status. RI was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 as determined by the Modification of Diet in Renal Disease equation using day -5 creatinine (Cr) values. Acute kidney injury (AKI) was identified and graded using standard Kidney Disease: Improving Global Outcomes criteria. Renal recovery was considered to occur if Cr was within .2 mg/mL of baseline by day +30. Fludarabine was considered DR if given at <90% of the recommended Food and Drug Administration label dose. Among 166 patients treated with CAR T cell therapy were 17 patients (10.2%) with baseline RI and 149 (89.8%) without RI. After CAR T cell infusion, the incidence of any grade AKI was not significantly different between patients with baseline RI and those without RI (42% versus 21%; P = .08). Similarly, severe grade 2/3 AKI was seen in 1 of 17 patients (5.8%) with baseline RI and in 11 of 149 patients (7.3%) without RI (P = 1). Decreased renal perfusion (28 of 39; 72%) was the most common cause of AKI, with cytokine release syndrome (CRS) contributing to 17 of 39 AKIs (44%). Progression-free survival (PFS) and overall survival (OS) did not differ between patients with RI and those without RI or between those who received standard-dose fludarabine and those who received reduced-dose fludarabine. In contrast, patients with AKI had worse clinical outcomes than those without AKI (multivariable PFS: hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2 to 3.7; OS: HR, 3.9; 95% CI, 2.1 to 7.4). Notably, peak inflammatory cytokine levels were higher in patients who experienced AKI. Finally, we describe 2 patients with end-stage renal disease (ESRD) on dialysis who received lymphodepletion and CAR T cell therapy. Baseline renal function did not affect renal or efficacy outcomes after CAR T cell therapy in DLBCL. On the other hand, patients with AKI went on to experience worse clinical outcomes. AKI was commonly related to CRS and high peak inflammatory cytokine levels. CAR T cell therapy is feasible in patients with ESRD and requires careful planning of lymphodepletion.

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data were censored at day 100. Grade ≥ 3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥ 3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 and 100 were 50% bacterial and 42% viral; only 13% were grade ≥ 3. On univariate analysis, high pre-CAR-T marrow myeloma burden (≥ 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥ 3 anemia at pre-LD were associated with grade ≥ 3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.

Mindfulness in Adolescent and Young Adult (AYA) Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT): A Qualitative Study.

Previous adolescent and young adult (AYA) research suggests patients undergoing hematopoietic stem cell transplantation (HSCT) experience severe physiological stress. The goal of this study was to identify unmet needs, interests, and preferences for mindfulness to inform the development of a mindfulness-based stress reduction intervention. Semi-structured interviews were conducted at three time points: prior to (n = 20), immediately after (n = 13), and three months post HSCT (n = 16) in the same AYA patients. Interviews assessed stress reduction strategies used, interest in mindfulness, and current quality of life. Three major thematic categories emerged from interview data across all time points: Concerns, Coping Strategies, and Mindfulness Activities. Prior to HSCT, two additional themes emerged including: Hope for the Future and Getting the Body Moving-Physical Activity. Most participants were not familiar with the term "mindfulness" prior to HSCT; but after being provided the definition of mindfulness, participants expressed interest in an online mindfulness-based intervention (e.g., ZOOM), stating: "I think it's necessary" and "It would definitely be useful". Participants suggested an intervention immediately following HSCT may decrease isolation concerns stating: "[in the hospital] You kind of feel like a hamster in a cage" and "you obviously have a lot of time to just be sitting by yourself in a hospital room". The results suggest that a mindfulness-based online intervention is of interest to AYA HSCT patients and may be beneficial in decreasing physiological stress and improving quality of life.