Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity.

ABSTRACT: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell-associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.

Autologous transplant vs chimeric antigen receptor T-cell therapy for relapsed DLBCL in partial remission.

The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.

Autologous stem cell transplant in fit patients with refractory or early relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy.

Chimeric antigen receptor T-cell therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (e.g., lack of resources for chimeric antigen receptor T-cell therapy, chemosensitive relapses). We retrospectively studied 230 patients with refractory or early relapsed DLBCL who underwent ST and ASCT. The median line of ST was one (range, 1-3). Best response before ASCT was complete response in 106 (46%) and partial response in 124 (54%) patients. The median follow-up after ASCT was 89.4 months. The median progression-free (PFS) and overall survival (OS) were 16.1 and 43.3 months, respectively. Patients relapsing between 6 to 12 months after frontline therapy had a numerically better median PFS (29.6 months) and OS (88.5 months). Patients who required one line of ST, compared to those requiring more than one line, had a better median PFS (37.9 vs. 3.9 months; P=0.0005) and OS (68.3 vs. 12.0 months; P=0.0005). Patients who achieved complete response had a better median PFS (71.1 vs. 6.3 months; P<0.0001) and OS (110.3 vs. 18.9 months; P<0.0001) than those in partial response. Patients who achieved complete response after one line of ST had the most favorable median PFS (88.5 months) and OS (117.2 months). Post-ASCT survival outcomes of patients with refractory or early relapsed DLBCL appeared reasonable and were particularly favorable in those who required only one line of ST to achieve complete response before ASCT, highlighting the role of this procedure in select patients with chemosensitive disease.

Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.

Allogeneic haematopoietic cell transplant in patients with relapsed/refractory anaplastic large cell lymphoma.

The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.8; p < 0.001) and refractory disease at allo-HCT (HR 3.2, 95% CI 1.6-6.2; p < 0.001) were predictive of inferior OS. Similarly, African-American race (HR 2.1, 95% CI 1.3-3.4; p = 0.003), other minority race (HR 2.5, 95% CI 1.2-5.3; p = 0.02) and refractory disease (HR 2.2, 95% CI 1.2-4.3; p = 0.01) were predictive of inferior PFS. These data, demonstrate that allo-HCT can result in durable disease control in a sizable proportion of patients with R/R ALCL. Refractory disease and racial minority status predicted inferior allo-HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL after allo-HCT are driven by differences in disease biology or disparities in post allo-HCT care, or both, requires further investigation.

Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies.

Several CD19-targeting CAR-T cells are used to treat leukemias and lymphomas; however, relapsed and/or refractory (R/R) disease is still observed in a significant number of patients. Additionally, the success of CD19-CAR-T cell therapies is not uniform across hematological malignancies, particularly in chronic lymphocytic leukemia (CLL). In this study, we present the development of a novel CAR-T cell therapy targeting B-cell activating factor receptor (BAFF-R), a key regulator of B-cell proliferation and maturation. A new monoclonal antibody against BAFF-R was generated from a hybridoma clone and used to create a novel MC10029 CAR construct. Through a series of in vitro and in vivo models using the Nalm-6 cell line for leukemia and the Z138 cell line for lymphoma, we demonstrated the antigen-specific cytotoxicity of MC10029 CAR-T cells against tumor cells. Additionally, MC10029 CAR-T cells exhibited potent antitumor effects against CD19 knockout tumor cells, mimicking CD19-negative R/R disease. MC10029 CAR-T cells were specifically targeted to CLL, in which BAFF-R is nearly always expressed. The cytotoxicity of MC10029 CAR-T cells was first shown in the MEC-1 CLL cell line, before we turned our efforts to subject-derived samples. Using healthy donor-engineered MC10029 CAR-T cells against enriched primary tumor cells, followed by subject-derived MC10029 CAR-T cells against autologous tumor cells, we showed the efficacy of MC10029 CAR-T cells against CLL subject samples. With these robust data, we have advanced to the production of MC10029 CAR-T cells, using GMP lentivirus, and obtained an IND approval in preparation for a Phase 1 clinical trial.

Consolidative radiotherapy for residual fluorodeoxyglucose activity on day +30 post CAR T-cell therapy in non-Hodgkin lymphoma.

Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.

Allogeneic transplant following CAR T-cell therapy for large B-cell lymphoma.

Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT in LBCL patients following CAR T failure. Eighty-eight patients with relapsed, refractory LBCL received an alloHCT following anti-CD19 CAR T failure. The median number of lines of therapy between CAR T infusion and alloHCT was one (range, 0-7). Low intensity conditioning was used in 77% (n=68) and peripheral blood was the most common graft source (86%, n=76). The most common donor types were matched unrelated donor (39%), followed by haploidentical (30%) and matched related donor (26%). Median follow-up of survivors was 15 months (range, 1-72). One-year overall survival, progression-free survival, and graft-versus-host disease-free relapse-free survival were 59%, 45%, and 39% respectively. One-year non-relapse mortality and progression/relapse were 22% and 33% respectively. On multivariate analysis, <2 lines of intervening therapy between CAR T and alloHCT and complete response at time of alloHCT were associated with better outcomes. In conclusion, alloHCT after CAR T failure can provide durable remissions in a subset of patients.

Impact of conditioning regimen intensity on the outcomes of peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma patients undergoing allogeneic transplant.

There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18-65 years), undergoing allo-HCT between 2008-2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79-1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61-1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98-1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92-1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3-4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46-0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.

Comparative study of therapy-related and de novo adult b-cell acute lymphoblastic leukaemia.

We report a comparative analysis of patients with therapy-related acute lymphoblastic leukaemia (tr-ALL) vs de novo ALL. We identified 331 patients with B-ALL; 69 (21%) were classified as tr-ALL. The most common prior malignancies were breast (23·2%) and plasma cell disorders (20·3%). Patients with tr-ALL were older (median 63·2 vs. 46·2 years, P < 0.001), more often female (66·7% vs. 43·5%, P < 0·001), and more likely to have hypodiploid cytogenetics (18·8% vs. 5·0%, P < 0·001). In multivariable analysis, patients with tr-ALL were less likely to achieve complete remission [odds ratio (OR) = 0·16, P < 0·001] and more likely to be minimal residual disease-positive (OR = 4·86, P = 0·01) but had similar OS after diagnosis and allo-haematopoietic cell transplantation.

Post-relapse survival in Waldenstrom macroglobulinemia patients experiencing therapy failure following autologous transplantation.

Waldenström macroglobulinemia (WM) is a rare B-cell lymphoproliferative malignancy. Autologous hematopoietic cell transplantation (auto-HCT) is considered in a subset of WM patients with relapsed disease. While registry data has shown a benefit for auto-HCT in relapsed WM, there is a paucity of data on outcomes of patients relapsing after auto-HCT. Eligibility criteria included adult patients with relapsed/refractory WM who underwent auto-HCT between 2007 and 2017. The primary endpoint was post-relapse overall survival (PR-OS). Secondary endpoints were to identify factors prognostic of PR-OS. Of the 48 patients with WM who underwent auto-HCT, 22 (46%) experienced relapse following auto-HCT. Median PR-OS of relapsed WM patients after auto-HCT (n = 22) was not reached (NR) (95% confidence interval [CI]: 17.5 months-NR). Among patients who relapsed <1 year versus ≥1 year from auto-HCT, the median PR-OS was 18.4 months (95%CI: 0.8-NR) months and NR (95%CI: 17.5-NR), respectively (p = 0.06). Of note, disease status at the time of transplant, CR/VGPR versus partial remission did not appear to impact PR-OS. The median PR-OS was significantly longer in patients who received ibrutinib in the post-transplant setting compared to those who did not (NR vs. 18.4 months, 95%CI: 9.1-NR, p = 0.02). On univariable analysis, the presence of complex karyotype (RR = 4.87, 95% CI = 1.22-19.53) and a higher number of prior lines of therapy (RR = 1.81, 95% CI = 1.23-2.67) were associated with a significantly higher risk of relapse. This is the only study to date that evaluated outcomes of WM patients who relapsed following auto-HCT and provides a benchmark for future trials evaluating survival following auto-HCT relapse.

Clinical characteristics, prognostic indicators, and survival outcomes in intravascular lymphoma: Mayo Clinic experience (2003-2018).

Intravascular lymphoma (IVL) is a rare extranodal non-Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003-2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS-IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non-CNS-IVL patients with abnormal FDG-PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS-IVL and 63.5% (35/55) had non-CNS-IVL. CNS-IVL group consists of clinically isolated CNS involvement (CNS-only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M-IVL) (14.5%; 8/55). Non-CNS-IVL group consists of clinically isolated skin involvement (skin-only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P-IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B-cell IVL. Rituximab + high-dose methotrexate-based regimen were used in 75% (12/16) of CNS-IVL patients and RCHOP in 60% (17/28) of non-CNS-IVL patients. Estimated 5-year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin-only IVL was associated with excellent survival. Platelet count <150x109 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

Follicular lymphoma grade 3: a comprehensive review.

Follicular lymphoma (FL) is a heterogeneous entity with disparate outcomes based on clinical and pathologic characteristics. An increasingly detailed understanding of high-grade FL (grade 3) has led to the identification of separate categories of FL3A and FL3B. Recently, genomic studies have made much progress in delineating the genetic differences between FL3A and FL3B. Although a general consensus exists that FL3B follows an aggressive course matching that of diffuse large B-cell lymphoma, there is less certainty regarding the course of FL3A. Uncertainty also exists regarding the management of high-grade FL. Given that a majority of the prospective landmark trials in FL have excluded patients with high-grade FL, most of the available evidence is retrospective. This review summarizes the recent advances in the management of high-grade FL.

Impact of Benzodiazepine Use on Length of Stay and 30-Day ED Visits among Hospitalized Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: This study assesses the impact of benzodiazepine (BNZ) use on length of stay (LOS) and 30-day emergency department (ED) visits after hematopoietic stem cell transplant (HSCT). METHODS: Adult patients (18 years and older) who underwent an allogeneic or an autologous HSCT from 2015 to 2018 at the study site were included. Five multivariable models were used for both allogeneic and autologous HSCT: BNZ-naïve status, diazepam equivalent daily dosage (DEDD; 0 vs any), DEDD (excluding 0), ED visits, and LOS. RESULTS: BNZ-naïve autologous HSCT recipients were less likely to use any BNZs in the hospital (odds ratio [OR] 0.07, P < 0.001). If prescribed BNZs, then they used a lesser amount (incidence rate ratio 0.39, P < 0.001). BNZ-naïve autologous HSCT recipients were less likely to experience a 30-day ED visit (OR 0.17, P = 0.009). BNZ-naïve allogeneic HSCT recipients were also less likely to use any BNZ than previous users (OR 0.11, P = 0.014). Patient characteristics influenced BNZ naïvety, DEDD usage, LOS for autologous patients, and BNZ naïvety and DEDD for allogeneic patients. CONCLUSIONS: BNZ use resulted in increased 30-day ED visits after autologous HSCT. BNZ-naïve recipients were less likely to use BNZs during hospital stays; if they required BNZs, then it was in lower dosages.

African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States.

BACKGROUND: Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. METHODS: This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). RESULTS: African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. CONCLUSIONS: Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.

Second allogeneic haematopoietic cell transplantation using HLA-matched unrelated versus T-cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia.

Optimal donor choice for a second allogeneic haematopoietic cell transplant (allo-HCT) in relapsed acute myeloid leukaemia (AML) remains unknown. We compared overall survival (OS) using registry data from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) involving 455 adults who received a second allo-HCT from a human leucocyte antigen (HLA)-matched unrelated (MUD) (n = 320) or a haploidentical (n = 135) donor. Eligibility criteria required adults aged ≥18 years who received a second allo-HCT for treating AML relapse between 2005 and 2019. The primary end-point was OS. There was no statistically significant difference in the median (interquartile range) age between the groups, MUD 46 (35-58) versus haploidentical 44 (33-53) years (P = 0·07). The median OS was not different between the MUD and the haploidentical groups (10 vs. 11 months, P = 0·57). Similarly, the 2-year OS was 31% for the MUD and 29% for the haploidentical donor groups. The OS was worse if the procedure was performed with active AML [hazard ratio (HR) 1·42, 95% confidence interval (CI) 1·07-1·89; P = 0·02]. Conversely, a longer time from first allo-HCT to relapse (>13·2 months) was associated with better OS (HR 0·50, 95% CI 0·37-0·69; P < 0·0001). The results of the present analysis limit the ability to recommend one donor type over another when considering a second allo-HCT for relapsed AML. Our findings highlight that best OS is achieved when receiving the second allo-HCT in complete remission.

Ruxolitinib resistance or intolerance in steroid-refractory acute graft-versus-host disease - a real-world outcomes analysis.

Ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. Ruxolitinib-resistant aGVHD was identified in 48/307 patients. Among patients receiving additional therapy, the overall response rate to next therapy was 36%. Median survival was 21 days. Ruxolitinib intolerance led to treatment discontinuation in 16/307 patients. Ten intolerant patients received additional therapy with 50% experiencing continued improvement of aGVHD. Median survival was 50 days in these patients. These data serve as a baseline for future SR-aGVHD studies.

Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation.

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

Efficacy of proteasome inhibitor-based maintenance following autologous transplantation in multiple myeloma: A systematic review and meta-analysis.

INTRODUCTION: Lenalidomide maintenance, commonly prescribed in the postautologous transplantation (AHCT) setting for multiple myeloma (MM), is associated with development of secondary primary malignancies (SPM). Proteasome inhibitor maintenance (PIM) has also been evaluated in MM. We conduct a systematic review/meta-analysis to assess the efficacy of PIM in MM. METHODS: Performing a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019, we extracted data on clinical outcomes related to benefits (OS, PFS, and depth of hematologic response [DOHR]) and harms (SPM and adverse events). 2144 references were identified; three studies were eligible for inclusion. RESULTS: A total of 1760 patients were included in the analysis; 507 patients received bortezomib and 395 received ixazomib maintenance. Control arms were either placebo (n = 261) or thalidomide (n = 358). PIM did not improve OS (HR 0.88, 95% CI 0.73-1.05, P = .15) but improved PFS (HR 0.77, 95% CI 0.69-0.86, P ≤ .00001) and DOHR (HR 0.88, 95% CI 0.79-0.98, P = .02) compared with control. There were no significant differences between PIM and control regarding SPM (p = NS) and ≥grade 3 peripheral neuropathy (PN) (p = NS). CONCLUSIONS: PIM following AHCT in MM improves PFS and DOHR without an increase in development of SPM or severe PN compared with placebo/thalidomide.

Impact of hypoalbuminemia on the prognosis of relapsed/refractory B-cell lymphoma treated with axicabtagene ciloleucel.

INTRODUCTION: Hypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi-cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B-cell lymphoma. METHODS: We conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi-cel. RESULTS: This analysis included 81 patients. Two patients had no available SA levels preceding axi-cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1-year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups. CONCLUSION: Notwithstanding the limitations related to the relatively small sample size, axi-cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.