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PURPOSE Epcoritamab is a subcutaneously administered CD3xCD20 T-cell–engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes. PATIENTS AND METHODS In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037 ), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee. RESULTS As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20‐83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell–associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event. CONCLUSION Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P = .001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P = .01), and chronic GI GvHD (21% versus 31%, P = .006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGcHD rate after Haplo/PTCY was also lower (hazard ratio [HR] = .4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR = .6, P = .01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR = .6, P = .04). Mortality rate was higher (HR = 1.6, P = .03) within, but not after (HR = .9, P = .6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.

Introduction: Immune checkpoint blockade of programmed death-1 (PD-1) receptor and its ligand (PD-L1) has contributed to efficacy in many tumor types, with clinical responses observed in a proportion of patients (pts) with Hodgkin lymphoma and rare non-Hodgkin lymphoma subtypes. A recent study demonstrated that combination treatment with anti-PD-L1 and anti-CD38 agents contributed to a stronger anti-tumor immune response compared with anti-PD-L1 monotherapy. Isatuximab, an anti-CD38 monoclonal antibody, is approved for use in multiple myeloma. Cemiplimab, an anti-PD-1 monoclonal antibody, is approved for use in cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer. Methods: This Phase 1/2 open-label study (NCT03769181) was designed to assess the safety, tolerability, and efficacy of isatuximab in combination with cemiplimab (Isa+Cemi) in pts with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). The primary objectives of Phase 1 were to characterize the safety and tolerability of Isa+Cemi and to confirm the recommended Phase 2 dose. Phase 2 used a Simon's 2-stage design to assess the complete response rate in Cohort A1 (anti-PD-1/PD-L1 naïve cHL; n=18; median age, 36 years; 55.6% male; ≥2 prior regimens, 100%) and to assess the objective response rate in Cohorts A2 (cHL progressing after PD-1/PD-L1 therapy; n=12; median age, 33 years; 58.3% male; ≥2 prior regimens, 100%), B (DLBCL; n=17; median age, 64 years; 70.6% male; ≥2 prior regimens, 100%), and C (PTCL; n=11; median age, 69 years; 63.6% male; ≥2 prior regimens, 9.1%). Pts received Isa+Cemi for up to 96 weeks. In Phase 1, the isatuximab dose was 10 mg/kg every week (Cycle 1), every 2 weeks (Cycle 2-6), or every 3 weeks (Cycle 7+). The cemiplimab dose was 250 mg every 2 weeks (Cycle 1-6) or 350 mg every 3 weeks (Cycle 7+). An interim analysis was performed when the last pt in Phase 2 was followed up for 24 weeks. The efficacy evaluation was based on Simon's 2-stage design with 85% power at a 5% 1-sided alpha level for each cohort. At least 8 (44.4%) and 3 (30.0%) responses were required in Cohorts B and C, respectively, in Phase 2 Stage 1 to advance to Phase 2 Stage 2. Results: Isa+Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed, confirming the recommended Phase 2 dose. Treatment-emergent adverse events (TEAEs) were reported in 83.3% (Cohort A1) and 100% (Cohorts A2, B, C) of pts. Grade ≥3 TEAEs occurred in 5.6%, 8.3%, 70.6%, and 81.8% of pts in Cohorts A1, A2, B, and C, respectively. There were no pts in Cohorts A1 or A2 who reported TEAEs leading to definitive discontinuation; 5.9% and 27.3% of pts in Cohorts B and C experienced TEAEs leading to definitive discontinuation. No Grade 5 TEAEs with fatal outcome were reported in Cohorts A1 or A2. There were 4 deaths reported during the on-treatment period in Cohort B (progressive disease, n=2; intestinal perforation, n=1; urinary tract infection, n=1) and 2 in Cohort C (unknown, n=1; progressive disease, n=1). Infusion reactions were reported in 38.9%, 75.0%, 52.9%, and 72.7% of pts in Cohorts A1, A2, B, and C, respectively; there was 1 (9.1%) Grade ≥3 infusion reaction reported in Cohort C. Pharmacokinetics (PK) analyses suggested no effect of cemiplimab on isatuximab PK, and vice versa. Based on Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of pts in the all-treated population achieved a complete or partial response. Median progression-free survival was 8.38 months (95% CI: 2.72-not calculable [NC]), 8.28 months (95% CI: 2.6-NC), 2.37 months (95% CI: 0.46-2.69), and 2.66 months (95% CI: 0.43-2.99) in Cohorts A1, A2, B, and C, respectively. Conclusion: In this study, Isa+Cemi had a manageable safety profile. Clinical efficacy was observed in pts with cHL, with increased responses observed in pts who had not previously received anti-PD-1/PD-L1 therapy compared with those who progressed on anti-PD-1/PD-L1 therapy. For Cohorts B (DLBCL) and C (PTCL), results of the interim efficacy analysis did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Most pts with DLBCL were primary refractory/bulky and discontinued rapidly, which may have contributed to the lack of activity with this combination. Disclosures Carlo-Stella: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Research Funding. Zinzani: TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sureda: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Casasnovas: TAKEDA: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy; ROCHE: Consultancy, Research Funding. Carpio: Regeneron, TAKEDA, Celgene, Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travels and accommodation. Bouabdallah: Abbvie: Honoraria; Sandoz: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Kim: Celltrion: Research Funding; Dong-A Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Sanofi: Research Funding; IGM Biosciences: Research Funding; Eisai: Research Funding; Johnson & Johnson: Research Funding; Roche: Research Funding. Cordoba: Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADCTherapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Koh: Pfizer: Consultancy; Jassen: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria; GSK: Honoraria; Roche: Honoraria; Takeda: Honoraria. Alves: Janssen, Cilag, Gilead, Takeda, Astrazeneca, Roche, Abbvie: Consultancy, Honoraria. Chamuleau: Gilead: Research Funding; Genmab: Research Funding; Celgene: Research Funding. Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Van Der Poel: Roche, Janssen, Abbvie: Honoraria. Abbadessa: Sanofi: Current Employment. Meng: Sanofi: Current Employment. Ji: Sanofi: Current Employment. Lepine: Sanofi: Other: Contractual relationship. Saleem: Sanofi: Current Employment. Ribrag: PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Epizyme: Honoraria, Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Based on the Phase III ICARIA-MM study, isatuximab (Sarclisa) is approved in a number of countries in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Based on the Phase III IKEMA study, isatuximab in combination with carfilzomib and dexamethasone is approved in the United States for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy, and in the European Union for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Cemiplimab (Libtayo) is an anti-PD-1 antibody approved for the treatment of the following: 1) patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation; 2) patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate; and 3) patients with NSCLC and high tumor PD-L1 expression as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations, and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic.

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65–80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1–24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1–6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69–91%) vs. 59% (45–72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl).

Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

Importance Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. Objective To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. Design, Setting, and Participants This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. Interventions/Exposures Allo-HCT from an older MSD (donor age ���50 years) or a younger MUD (donor age ���35 years). Main Outcomes and Measures The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. Results Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P���=���.02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P���=���.07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P���

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus

Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of

Background There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. Objective The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. Methods Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). Results Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. Conclusions Return of individual PRO results seems to meet patients’ wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice. Trial Registration Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790 International Registered Report Identifier (IRRID) RR2-10.1186/s13063-017-1943-2

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age >= 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose

Context: Treatment options that are more tolerable, readily available, and capable of inducing deep and durable responses are needed in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Epcoritamab is a novel, subcutaneous (SC) CD3xCD20 bispecific antibody with preliminary potent antitumor activity. Objective: Report primary results from the LBCL expansion cohort in the phase 2 study of SC epcoritamab in patients with R/R B-cell NHL (EPCORE NHL-1; NCT03625037). Patients: Adults with R/R CD20+ LBCL were included. Patients had DLBCL (including double/triple-hit and transformed), high-grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), or follicular lymphoma (FL) grade (G) 3B. As of January 31, 2022, 157 patients were treated. Interventions: Patients received epcoritamab (priming and intermediate doses followed by 48 mg) as 1-mL SC injections (QW, cycle [C] 1–3; Q2W, C4–9; Q4W, C≥10) until disease progression or unacceptable toxicity. Results: The 157 patients had a median of 3 (range, 2–11) prior lines of therapy (LOT), 61 (38.9%) received prior CAR T, 61% had primary refractory disease, and 83% were refractory to the last LOT. With a median follow-up of 10.7 mo, the overall response rate (ORR) by IRC (Lugano/PET-CT) was 63% with 39% complete response (CR). ORR/CR rates were 69%/42% for CAR T–naive patients and 54%/34% for CAR T–exposed patients. Median duration of response was 12 mo overall and not reached among complete responders. ORR was similar across prespecified subgroups of age, prior LOT, and de novo or transformed disease. The most common treatment-emergent AEs were CRS (49.7%; 31.8% G1, 15.3% G2, 2.5% G3), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), and diarrhea (20.4%). Ten patients (6.4%) experienced ICANS; all but one event was G1–2, and the G5 ICANS was the only treatment-related death. Conclusions: Epcoritamab is a convenient, SC, off-the-shelf therapy that demonstrated clinically meaningful, compelling efficacy including deep and durable responses in a challenging-to-treat, highly refractory LBCL population. Efficacy was observed in both CAR T–exposed and CAR T–naive patients. The safety profile was manageable and consistent with previous findings. Funding: This study was funded by Genmab A/S and AbbVie.

INTRODUCTION: There is a lack of evidence about how Health-related Quality of Life (HRQoL), including psychosocial factors, might affect donation-related experiences and clinical markers in the context of hematopoietic stem cell (HSC) donation. The broader literature suggests that psychological factors, including anxiety and depression, are associated with higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. In this study, we aimed to evaluate whether pre-donation HRQoL markers predict toxicity profile and stem cell yield following PBSC donation in healthy donors. METHODS: The study population comprised adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) enrolled in the related donor safety study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HRQoL was assessed using the Short-Form-12 (SF-12) in RDSafe and SF-8 questionnaire in BMT CTN 0201 (higher score is better). The aims of this study were to (a) determine the impact of pre-donation HRQoL on peri-collection pain and acute toxicities experienced and (b) to investigate the pre-procedural HRQoL indicators on stem cells yield. RESULTS: URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more of apheresis (44% vs 21%). More RD collections were lower volume procedures (

In 2017, the European Medicines Agency approved rituximab biosimilars (R-biosimilars) for treatment of diffuse large B-cell lymphoma (DLBCL). Thereafter, the Netherlands was one of the first countries to implement R-biosimilars, given lower costs compared with rituximab originator (R-originator). This study’s objective was to investigate whether overall survival (OS) of patients with DLBCL receiving R-biosimilars is similar to patients treated with R-originator. DLBCL patients ≥18 years, diagnosed between 2014 and 2018, who received at least 1 cycle of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were identified in the Netherlands Cancer Registry. Patients were categorized into R-originator or R-biosimilars groups based on data from a central repository of the Dutch medicinal drug market. The primary end point was 3-year OS, defined as the time between diagnosis and all-cause death. By the end of 2018, 91% of purchased rituximab were biosimilars. In total, 4429 patients were identified with 876 in the R-biosimilars group and 3553 in the R-originator group. Patients in the R-biosimilars group less frequently received >6 cycles of R-CHOP compared with patients treated with R-originator (24% vs 30%, P = .003). The 3-year OS did not differ between patients treated with R-originator or R-biosimilars (73% vs 73%, P = .855). This was confirmed with a multivariable Cox regression analysis accounting for sex, age, International Prognostic Index score, and number of R-CHOP cycles. In conclusion, the 3-year OS is similar for patients treated with CHOP in combination with R-originator or R-biosimilars and, therefore, favors the use of R-biosimilars in DLBCL treatment management.

Use of ustekinumab in Crohn’s disease was approved in 2016, and consequently data regarding its real-world safety are still limited. We here present a 29-year-old woman with severe therapy-refractory Crohn’s disease, who developed an anaplastic large cell T cell lymphoma during treatment with ustekinumab.

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with tAML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

e19584 Background: This open-label, multicenter, phase 1b study evaluated the safety and efficacy of blinatumomab and pembrolizumab combination therapy in patients (pts) with R/R DLBCL (NCT03340766). Methods: Key inclusion criteria included adults with ECOG performance status ≤2 and life expectancy ≥12 weeks. In cycle 1, pts received a continuous intravenous (cIV) infusion of blinatumomab followed by step dosing to the target dose (TD; Table). After a 28-day treatment-free interval, cIV infusion of blinatumomab was administered for 28 days in cycle 2 with the same dose escalations as in cycle 1. Pembrolizumab 200 mg IV was administered once every 21 days starting on day 15 in cohort 1a, and on day 19 in cohorts 2a and 3a. Pts were premedicated with dexamethasone. Dose-limiting toxicities (DLT) were the primary endpoint. The maximum tolerated dose (MTD) was the highest dose level at which ≤1 of 6 or ≤2 of 10 pts experienced a DLT. Results: As of June 10, 2021, 31 pts were enrolled in cohorts 1a, 2a, and 3a (Table). DLTs occurred in 1 (10%) pt in cohort 1a (neutropenia) and 2 (40%) pts in cohort 3a (cognitive impairment, and elevated AST, ALP, and GGT levels). Treatment-emergent (TE) adverse events (AEs) were observed in 31 (100%) pts; grade ≥3 AEs occurred in 29 (94%) pts. The most frequent grade ≥3 TEAE attributed to blinatumomab was nervous system disorders (11 [35%]) and that attributed to pembrolizumab was blood and lymphatic system disorders (5 [16%]). Serious blinatumomab-related and pembrolizumab-related AEs were observed in 15 (48%) and 2 (6%) pts, respectively. Fourteen (45%) deaths occurred; none were treatment-related. Cohort 2a dose was determined as the MTD (Table). In cohort 2a, the objective response rate within 12 weeks of blinatumomab treatment was 30%; the median duration of response in responders (n = 8) was 176.5 (range: 28–680) days. Exposures of blinatumomab and pembrolizumab in this combination study were consistent with historical data for the individual agents. Conclusions: The cohort 2a dosing schedule with TD of 56 μg/day of blinatumomab was established as the MTD. The study was terminated after dose finding because the MTD of blinatumomab in combination with pembrolizumab was lower than the MTD of blinatumomab monotherapy, with no apparent efficacy gain. Clinical trial information: NCT03340766. [Table: see text]

Background In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival. Methods All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis. Results Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment. Conclusions Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.

BACKGROUND There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. OBJECTIVE The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. METHODS Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). RESULTS Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. CONCLUSIONS Return of individual PRO results seems to meet patients’ wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice. CLINICALTRIAL Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790 INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-017-1943-2

Simple Summary Treatment results of acute myeloid leukemia (AML) in elderly patients are unsatisfactory. We investigated in an open label randomized phase II study whether addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy would improve outcome in this population. 231 AML patients > 65 years of age were randomly assigned to receive standard chemotherapy with or without tosedostat for two cycles. We found that complete bone marrow leukemia clearance was not significantly different between both arms. After two years, survival was 33% for the standard arm versus 18% for the tosedostat arm. More patients died due to infectious complications in the tosedostat arm than after standard treatment. Also, a cardiac rhythm abnormality called atrial fibrillation was more often seen in the tosedostat arm. We conclude that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly patients with acute myeloid leukemia. Abstract Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) 90 or chemosensitive disease.

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85.

We assessed the impact of a prior malignancy diagnosis (PMD) – as a potential proxy for genetic cancer susceptibility – on the development of a second primary malignancy (SPM) and mortality in follicular lymphoma (FL) patients. From the nationwide Netherlands Cancer Registry, we selected all adult FL patients diagnosed in 1994-2012 (n = 8028) and PMDs and SPMs relative to FL, with follow-up until 2017. We constructed two Fine and Gray models – with death as a competing risk – to assess the association between a PMD and SPM incidence. A PMD was associated with an increased incidence of SPMs (subdistribution hazard ratio [SHR], 1.30; 95% confidence interval [CI], 1.03-1.64) – especially carcinomas of the respiratory tract (SHR, 1.83; 95% CI, 1.10-3.05) and cutaneous squamous cell carcinomas (SHR, 1.58; 95% CI, 1.01-2.45) – and a higher risk of mortality in a multivariable model (HR, 1.43; 95% CI, 1.19-1.71). However, when additionally adjusted for the receipt of systemic therapy and/or radiotherapy before FL diagnosis, only patients who received such therapies had an increased incidence of SPMs (SHR, 1.40; 95% CI, 1.02-1.93). In conclusion, patients with a PMD had a higher rate of SPMs and mortality than those without a PMD, which might have resulted from therapy-related carcinogenesis.

Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P

Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with hematologic malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P

Introduction Patients with high grade B cell lymphoma that harbor a MYC rearrangement with concomitant BCL2 and/or BCL6 rearrangements (double hit and triple hit (HGBL-DH/TH)) face a poor prognosis upon standard treatment with R-CHOP [Rosenwald, JCO 2019]. DA-EPOCH-R might yield higher complete metabolic remission (CMR) rates and longer disease free survival (DFS) as compared to R-CHOP, but improvement of overall survival (OS) has not been demonstrated [Dunleavy, Lancet Haematol 2018]. Tumors with MYC overexpression may be susceptible for immune checkpoint inhibition (CI) [Casey, Science 2016], providing a rationale for CI after reaching CMR to improve tumor immune surveillance for minimal residual disease (MRD) positive disease. Here, we present data of the planned interim analysis of 33/97 patients included in the HOVON-152 trial (NCT03620578). Methods HOVON-152 is a prospective, multi-center, single arm phase II trial. Inclusion criteria are newly diagnosed HGBL-DH/TH; age ≥ 18 year; WHO performance status 0-3; Ann Arbor stage II-IV. During the screening period for rearrangements patients receive 1 cycle of R-CHOP followed by 5 cycles of DA-EPOCH-R induction treatment. All patients receive intrathecal prophylaxis. All diagnostic lymphoma samples are centrally reviewed. PET-CT scans are performed at diagnosis, midterm and end-of-induction. Patients in CMR after induction treatment (Deauville 1-3 or a negative lymphoma biopsy in case of Deauville 4) proceed with Nivolumab consolidation (480 mg iv every 4 weeks) for one year. The primary objective is to improve 12 months DFS with Nivolumab consolidation from 70% to 85% in patients in CMR after induction treatment. Secondary objectives include evaluation of CMR rates, OS and safety. Exploratory side studies investigate blood-based biomarkers for response prediction by immune profiling using multicolor flow cytometry after 1 cycle of R-CHOP and molecular circulating tumor DNA (ctDNA) analyses using ClonoSEQ (Adaptive Biotechnologies, Seattle) after 1 cycle of R-CHOP and at midterm. Results From August 2018 to June 2021, 69 of planned 97 patients have been enrolled. Baseline characteristics of the first 33 patients included in the interim analysis are shown in Table 1. Dose adjustments of EPOCH (according to protocol) resulted in 48% of patients receiving dose level ≤1 and 52% dose level ≥ 2 at the last cycle. After induction, 20/33 patients (61%; 95% CI 42%-77%) reached CMR. 11/33 patients (33%) did not reach CMR and 2/33 (6%) patients went off protocol (due to progression). During DA-EPOCH-R, one patient (3%) experienced grade 5 AE (sepsis), 9 patients (27%) experienced a grade 4 AE, and 9 (27%) patients grade 3. Neurotoxicity led to dose adjustments or discontinuation of vincristine in 52% of the patients. In an amendment the vincristine dose was capped at 2 mg/cycle. Twenty patients received 6 cycles of Nivolumab consolidation. One patient had a grade 4 AE (neutropenia); 2 patients had a grade 3 AE (one lung infection and one colitis (reason for going off protocol)). The Data Safety Monitoring Board recommended to continue the trial. Exploratory biomarker analyses show that patients achieving CMR after DA-EPOCH-R (data available for 19/20 patients) have higher percentages of T cells (p=0.04) after 1 cycle of R-CHOP than patients that do not achieve CMR (data available for 12/13 patients). ctDNA analysis was possible in 16/28 patients (in 12/28 patients no clone could be detected for monitoring). 10/16 patients achieved CMR, of which 9/10 were negative for minimal residual disease (MRD) at midterm. The patient that was MRD positive at midterm relapsed shortly after CMR. 4/5 patients that did not achieve CMR were MRD positive at midterm. Conclusions Interim analysis of the HOVON-152 trial demonstrates that 61% (95% CI 42%-77%) of the patients with HGBL-DH/TH achieve CMR after induction with DA-EPOCH-R. Toxicity of DA-EPOCH-R consists mainly of neurotoxicity leading to a protocol amendment (dose cap of vincristine). Nivolumab consolidation is safe with only one patient going off protocol due to colitis. Biomarkers for CMR after induction with DA-EPOCH-R point out to ctDNA-based MRD negativity at midterm and to higher T percentages after 1 cycle of R-CHOP, supporting the hypothesis of contributive immune surveillance for response in patients with HGBL-DH/TH. The trial is ongoing. Figure 1 Figure 1. Disclosures Nijland: Roche: Research Funding; Nordic Nanovector: Research Funding; Takeda: Research Funding. Van Der Poel: Roche, Janssen, Abbvie: Honoraria. Klerk: Van Lanschot Kempen: Other: I have an investment porfolio which is managed by Van Lanschot Kempen as a portfolio manager (vermogensbeheerder). Van Lanschot Kempen invests on my behalf, and takes investment decisions on a discretionary basis. I am not involved in the investment decis. Pegtel: Exbiome BV: Current holder of individual stocks in a privately-held company; Takeda: Other: Travel compensation. Mutis: Novartis: Research Funding; ONK Therapeutics: Research Funding; Janssen: Honoraria; Takeda: Research Funding; Genmab: Research Funding. Zijlstra: Takeda: Research Funding. Kersten: BMS/Celgene: Consultancy; Kite/Gilead: Consultancy, Honoraria, Research Funding; Milteny Biotech: Consultancy; Novartis: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy. Chamuleau: Gilead: Research Funding; Genmab: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Nivolumab as immune checkpoint inhibitor (inhibiting PD-1) in consolidation phase for the treatment of DH/TH-HGBL patients.

Introduction: Peripheral T-cell lymphomas (PTCL) comprise a heterogenous group of mature T-cell neoplasms with generally an unfavorable prognosis. Presentation of PTCL with stage I(E) disease, according to the Ann Arbor classification, is uncommon. Clinical trials in diffuse large B-cell lymphoma (DLBCL) support the use of an abbreviated treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone combined with radiotherapy (combined modality therapy (CMT)) in case of stage I(E) disease. CMT in stage I(E) PTCL has been adapted in daily practice, but clinical trials are lacking. A recent population-based study conducted in Scandinavia indicated that the outcome in patients with limited stage PTCL is as poor as in patients with extensive disease. However, the outcomes of different treatment modalities were not analyzed. Aim: The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL in comparison to advanced stage PTCL. Methods: All newly diagnosed patients ≥ 18 years with stage I(E) PTCL who were diagnosed in 1989-2018 were identified in the Netherlands Cancer Registry (NCR). Survival follow-up was available through February 1, 2021. The PTCL subgroups analyzed included anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma (EATL) and peripheral T-cell lymphoma NOS (PTCL NOS). Patients were categorized according to treatment regimen, i.e. chemotherapy, chemotherapy followed by autologous stem cell transplantation (ASCT), radiotherapy, CMT, and no/other therapy. Calendar period analyses (1989-1999 and 2000-2018) were conducted to assess trends in primary therapy and overall survival (OS) over time. The calendar periods were defined according to the implementation of CMT in patients with limited stage DLBCL from approximately 2000 onward in the Netherlands. The primary endpoint was OS, defined as all-cause-death post-diagnosis. Results: From 1989 to 2018, 854 patients with a median age of 62 years were diagnosed with stage I(E) PTCL, accounting for 19% of all PTCL diagnoses. In stage I(E), the predominant PTCL subtype was PTCL NOS (40%, n=343). Furthermore, 26% (n=222) of patients were diagnosed with ALCL, 3% (n=28) with AITL, 11% (n=93) with EATL and 20% (n=168) with other histological subtypes. In contrast, for patients with advanced stage disease, 42% was diagnosed with PTCL NOS, 23% with ALCL, 24% with AITL, 6% with EATL and 5% with other histological subtypes . To evaluate treatment and survival outcome in patients with stage I(E) PTCL, patients with ALCL, AITL, PTCL NOS and EATL were included for further analyses (n=686). Patients with ALCL, AITL and PTCL NOS were most commonly treated with CMT (n=164; 28%) or chemotherapy only (n=154; 26%). Only 10 patients (1%) received chemotherapy followed by ASCT. The remaining patients were treated with either radiotherapy only (n=116; 20%) or received other/no therapy (n=149; 25%). More patients were treated with CMT in 2000-2018 as compared to 1989-1999 (36% versus 17%, p Overall, 5-year OS for all stage I(E) PTCL was 52%. There was no significant difference in outcome between the two time periods (53% vs. 52%, p=0.92). EATL had a worse prognosis when compared to ALCL, AITL and PTCL NOS (5-year OS 15% vs. 58%, respectively; p Conclusions: For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 58%. This compares favorably to the reported outcomes in advanced stage disease. EATL, even when presenting with limited stage disease, is associated with a very poor prognosis. CMT is associated with superior OS when compared to either chemotherapy or radiotherapy alone. Disclosures Van Der Poel: Roche, Janssen, Abbvie: Honoraria. Kersten: Kite/Gilead: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy; Miltenyi Biotech: Consultancy; Novartis: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy. Mutsaers: BMS: Consultancy; AstraZeneca: Research Funding. Woei-a-Jin: University Hospitals Leuven, Belgium: Current Employment; Recordati: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Kyowa Kirin: Research Funding.

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

TO THE EDITOR: We read with interest the article by [Giri et al][1][1][2] on overall survival (OS) among very elderly (age ≥80 years) patients with diffuse large B-cell lymphoma (DLBCL) diagnosed in the United States between 1983 and 2013. The authors concluded that the OS of these patients had

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a treatment option for patients with hematopoietic malignancies that is hampered by treatment-related morbidity and mortality, in part the result of opportunistic infections, a direct consequence of delayed T-cell recovery. Thymic output can be improved by facilitation of thymic immigration, known to require precommitment of CD34+ cells. We demonstrate that Delta-like ligand-mediated predifferentiation of mobilized CD34+ cells in vitro results in a population of thymocyte-like cells arrested at a T/natural killer (NK)–cell progenitor stage. On intrahepatic transfer to Rag2−/−γc−/− mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor–αβ+ mature T cells considerably faster than animals transplanted with noncultured CD34+ cells. This finding creates the opportunity to develop an early T-cell reconstitution therapy to combine with HSCT.