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Objective The purpose of this study was to investigate the efficacy and safety of NEPA for the prevention of CINV for HCT patients receiving BEAM therapy. Study Design This phase II, prospective, intention-to-treat, single-center, single arm study involved 43 adult patients who received NEPA and dexamethasone for prevention of CINV due to BEAM conditioning chemotherapy. An interim analysis, performed after 13 patients, determined utility versus futility and supported continuation to full enrollment. Descriptive statistics were used to report complete response (CR), complete protection (CP), incidence of emesis, and administration of rescue agents. A Kaplan-Meier curve depicted time to first emesis and first rescue medication. Patients self-reported levels of daily nausea descriptively via a CINV Questionnaire. Results By study end, 13 of 43 patients achieved a CR with an average of 10.6 emesis free days (SD 0.95) over the 11-day observation period, with no emetic events in any patient during the acute/chemotherapy phase. Nausea was well controlled throughout the acute therapy phase (Days 1–6) and increased during the delayed phase (Day 7–11) with a peak mean level of 2.79/10 at Day 10. Aside from lower grade (≤ 2) headaches, constipation and diarrhea were the most widely reported adverse effects. Conclusion The combination of NEPA and dexamethasone is safe and effective for the prevention of CINV in patients receiving BEAM conditioning therapy prior to HCT. The regimen demonstrated greater effectiveness in the acute phase versus the delayed phase, with low levels of nausea throughout the study period and complete emesis prevention during chemotherapy. NCT03097588 registered March 31, 2017.

Objective: The purpose of this study was to investigate the efficacy and safety of netupitant/palonosetron (NEPA) for the prevention of chemotherapy-induced nausea and vomiting (CINV) for hematopoietic cell transplantation (HCT) patients receiving BEAM therapy. Study Design: This phase II, prospective, intention-to-treat, single-center, single-arm study involved 43 adult patients who received NEPA and dexamethasone for the prevention of CINV due to BEAM conditioning chemotherapy. An interim analysis, performed after 13 patients, determined utility versus futility, and supported continuation to full enrollment. Descriptive statistics were used to report complete response (CR), complete protection, incidence of emesis, and administration of rescue agents. A Kaplan–Meier curve depicted time to first emesis and first rescue medication. Patients self-reported levels of daily nausea descriptively via a CINV Questionnaire. Results: By study end, 13 of 43 patients achieved a CR with an average of 10.6 emesis-free days (SD 0.95) over the 11-day observation period, with no emetic events in any patient during the acute/chemotherapy phase. Nausea was well-controlled throughout the acute therapy phase (Day 1–6) and increased during the delayed phase (Day 7–11) with a peak mean level of 2.79/10 at Day 10. Aside from lower grade (≤2), headaches, constipation, and diarrhea were the most widely reported adverse effects. Conclusion: The combination of NEPA and dexamethasone is safe and effective for the prevention of CINV in patients receiving BEAM conditioning therapy prior to HCT. The regimen demonstrated greater effectiveness in the acute phase versus the delayed phase, with low levels of nausea throughout the study period and complete emesis prevention during chemotherapy.

Follicular lymphoma (FL) is generally considered an indolent disease, although patients with relapsing FL experience progressively shorter durations of response to second or later lines of therapy. The ongoing ELARA trial in adult patients with relapsed/refractory (r/r) FL treated with tisagenlecleucel demonstrated an overall response rate of 86.2% and a complete response rate of 69.1%, with no treatment-related deaths. Tisagenlecleucel was administered in the outpatient setting in 18% of patients in ELARA; however, there is limited knowledge concerning the impact of inpatient versus outpatient tisagenlecleucel administration on healthcare resource utilization (HCRU) among patients with r/r FL. Here, we present the first HCRU analysis among patients with r/r FL who received tisagenlecleucel in the Phase II, single-arm, multicenter ELARA trial. HCRU was characterized using hospitalization data from day 1 to month 2 after tisagenlecleucel infusion. Information on length of stay, facility use, and discharge was assessed in patients who received tisagenlecleucel in the outpatient or inpatient setting. All costs were inflated to 2020 US dollars. As of August 3, 2021 (20-month median follow-up), 17/97 (18%) r/r FL patients were infused in an outpatient setting. Patients infused in the outpatient setting generally had favorable Eastern Cooperative Oncology Group performance status and Follicular Lymphoma International Prognostic Index scores, and less bulky disease at baseline. However, the outpatients had higher proportions of patients with grade 3A FL, primary refractory disease, and5 lines of prior therapy compared with inpatients. Forty-one percent of patients treated in the outpatient setting did not require hospitalization within 30 days after infusion, and outpatients who did require hospitalization had a shorter average length of stay compared with inpatients (5 versus 13 days). No outpatients required intensive care unit (ICU) admission, whereas 9% of inpatients were admitted to the ICU. The mean postinfusion hospitalization costs were $7477 and $40,054 in the outpatient and inpatient settings, respectively. Efficacy between both groups was similar. Tisagenlecleucel can be safely administered to some patients in the outpatient setting, which may reduce HCRU for patients with r/r FL.

INTRODUCTION AND OBJECTIVE:An estimated 25% of inpatients require urethral catheterization during their hospital stay. Complications from iatrogenic traumatic urethral catheterization (TUC) are not...

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IMPORTANCE: Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. OBJECTIVE: To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. INTERVENTIONS: Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. RESULTS: Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P

Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8–20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8–78.3) and ORR 86.2% (95% confidence interval, 77.5–92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients., The study was sponsored and designed by Novartis Pharmaceuticals Corporation and was approved by the IRB at each participating institution.

Background: Single-agent polatuzumab vedotin (pola) and obinutuzumab (G) demonstrated safety/clinical activity in separate B-cell non-Hodgkin lymphoma (B-NHL) trials. Methods: Open-label, non-randomised, phase 1b/2 study (ROMULUS) of patients with relapsed/refractory (R/R) B-NHL evaluating safety/efficacy of pola 1·8 mg/kg + G 1000 mg in 21-day cycles, up to eight cycles. Primary objectives were safety/tolerability and anti-tumour response. Findings: Eighty-eight patients were enrolled and received ≥1 dose of any study drug; 43 patients with R/R follicular lymphoma (FL) and 45 with R/R diffuse large B-cell lymphoma (DLBCL). Grade 3–4 AEs occurred in 48·5% (n=48/88) of patients, most commonly, neutropenia (18·6%; n=18). In R/R FL, the most frequent any-grade adverse event (AE) was fatigue (n=23/43; 53·5%) and in R/R DLBCL diarrhoea (n=16/45; 35·6%). In R/R FL, the complete response (CR) rate (by independent review committee) was 36·1% (n=13/36; 90% confidence interval [CI]: 22·9–51·2) with an objective response rate (ORR) of 66·7% (n=24/36; 90% CI: 51·7–79·5). The ORR in R/R DLBCL was 19·4% (n=6/31; 90% CI: 8·8–34·7; no CRs). In R/R FL, investigator-assessed median duration of response was 8·5 months (interquartile range [IQR]: 6×3–9×7) and in R/R DLBCL was 3·7 months (IQR: 3×3–not estimable [NE]); median progression-free survival was 11·5 months (IQR: 7×8-12×4) and 2·8 months (IQR: 1×5-6×3); and median overall survival was not reached and 10·7 months, respectively. Interpretation: While the anti-tumour activity of pola (1.8 mg/kg)-G in R/R DLBCL was modest, pola-G warrants further investigation as a treatment for R/R FL. Trial Registration: www.clinicaltrials.gov (NCT01691898). Funding Statement: F. Hoffmann-La Roche. Declaration of Interests: T.P. has received research support from AbbVie and Pharmacyclics, and reports advisory board participation for Genentech, Inc., Bayer, Gilead, Pharmacyclics, Incyte, and Seattle Genetics. M.B. has no disclosures; the clinical and intellectual work on this paper was performed prior to employment with the Cigna Corporation and does not reflect the opinions or support of the Cigna Corporation. A.I.C. has acted as a consultant and has received research funding from Genentech, Inc. J.E. has nothing to disclose. A.C. reports advisory board participation for Celgene, Janssen, and iQone, and has received lecture fees from Celgene, Janssen, F. Hoffman-La Roche Ltd, and Servier. C.D. has served as a consultant/advisory board participant for Bristol-Myers Squibb, Celgene, Merck, Genentech, Inc./F. Hoffman-La Roche Ltd, and Seattle Genetics, and has received research support from Seattle Genetics, Bristol-Myers Squibb, Merck, Genentech, Inc., Incyte, LAM Therapeutics, Millennium/Takeda, MEI Pharma, and Trillium. J.C. is an employee of F. Hoffmann-La Roche Ltd. D.R. was a consultant to Genentech, Inc. at the time the study was carried out. J.H. is an employee of Genentech, Inc. F.M. has participated in advisory boards for Celgene, F. Hoffman-La Roche Ltd, Gilead, Bristol-Myers Squibb, Epizyme, and Bayer, and reports receiving lecture fees from Celgene, Janssen, F. Hoffman-La Roche Ltd, and Novartis, and research support from AbbVie, Pharmacyclics, and advisory board fees from Genentech, Inc., Bayer, Gilead, Pharmacyclics, Incyte, and Seattle Genetics. I.W.F. has acted as a consultant for AbbVie, Seattle Genetics, TG Therapeutics, and Verastem Oncology, and has received research funding from Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Inc., Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karo Pharma, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals, F. Hoffman-La Roche Ltd, TG Therapeutics, Trillium Therapeutics, AbbVie, ArQule, BeiGene, Curis Inc., FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem Oncology, Gilead Sciences, Astra Zeneca, Juno Therapeutics, Unum Therapeutics, and MorphoSys AG. Ethics Approval Statement: Institutional review boards/ethics committees approved the protocol. The study was conducted in accordance with the principles of the Declaration of Helsinki, the International Council for Harmonisation guidelines for Good Clinical Practice, and country-specific laws and regulations. All patients provided written informed consent.

Hematopoietic cell transplantation (HCT) is a key treatment modality in the management of advanced Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Autologous HCT (autoHCT) can be curative for relapsed or refractory HL and diffuse large B-cell lymphoma. In low-grade lymphoma, autoHCT also improves outcomes, and allogeneic HCT (alloHCT) can be curative in multiply relapsed disease. HCT is also effective in less common lymphomas like peripheral T-cell lymphoma and primary central nervous system (CNS) lymphoma. Maintenance therapy after transplant improves outcomes in HL, follicular lymphoma, and mantle cell lymphoma.

The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression after autologous hematopoietic stem-cell transplantation (auto-HSCT). Results showed that BV significantly improved progression-free survival (PFS) vs placebo plus best supportive care alone. At 5-year follow-up, BV continued to provide patients with sustained PFS benefit; 5-year PFS was 59% (95% confidence interval [CI], 51-66) with BV vs 41% (95% CI, 33-49) with placebo (hazard ratio [HR], 0.521; 95% CI, 0.379-0.717). Similarly, patients with ≥2 risk factors in the BV arm experienced significantly higher PFS at 5 years than patients in the placebo arm (HR, 0.424; 95% CI, 0.302-0.596). Upfront consolidation with BV significantly delayed time to second subsequent therapy, an indicator of ongoing disease control, vs placebo. Peripheral neuropathy, the most common adverse event in patients receiving BV, continued to improve and/or resolve in 90% of patients. In summary, consolidation with BV in adult patients with cHL at high risk of relapse or progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. Physicians should consider each patient's HL risk factor profile when making treatment decisions. This trial was registered at www.clinicaltrials.gov as #NCT01100502.

Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF.

Background: Follicular lymphoma (FL) is the second most frequently diagnosed Non-Hodgkin lymphoma subtype in Western countries. Patients often undergo multiple lines of therapy over many years throughout the course of their disease with worse survival after each successive line of therapy. Recent findings from the ELARA trial showed that tisagenlecleucel, a chimeric antigen receptor (CAR)-T cell therapy, had durable complete response rate of 66.0%, with a probability of 79% (95% CI, 66%-87%) to remain in response ≥6 months (overall response rate 86.2%) in patients with relapsed or refractory (r/r) FL. Prior evidence in patients with r/r diffuse large B-cell lymphoma demonstrated that tisagenlecleucel can be safely infused in an outpatient setting and may reduce healthcare resource utilization (HCRU) (Lyman et al, 2020). we present the first HCRU among patients with r/r FL who received tisagenlecleucel in the ELARA trial. Methods: ELARA is a Phase II, single-arm, multicenter study of tisagenlecleucel in adult patients with r/r FL. All patients underwent lymphodepleting chemotherapy with fludarabine and cyclophosphamide or bendamustine, before receiving a single IV infusion of tisagenlecleucel (0.6-6×10 8 CAR-positive viable T cells) that was administered at the investigator's discretion in either the inpatient or outpatient setting. Patients were followed for a median of 11 months, and HCRU was characterized using hospitalization data collected from the first day of infusion up to the second month after treatment, the time period wherein occurrence of CAR-T cell-related adverse events (AEs) such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are most frequent. Information on the length of stay (dates of admission), hospital facilities used, and discharge information were assessed. Healthcare costs associated with hospitalizations and intensive care unit (ICU) admissions were estimated by applying unit costs obtained from published literature. All costs were from healthcare system perspective and were inflated to 2020 US Dollars. Results: Among 97 patients with r/r FL who received tisagenlecleucel infusion, 17 patients (18%) were infused in an outpatient setting and 80 patients (82%) were admitted for inpatient infusion and monitoring. Of the 30 clinical trial sites, 4 sites in US and 1 site in Australia used outpatient administration; at these sites, 68% (17 of 25) of the patients were treated in an outpatient setting. Patients treated in the outpatient setting were more likely to have ECOG performance status of 0 and a more favorable FLIPI score, but more frequently had grade 3A FL, primary refractory disease, and >5 lines of prior antineoplastic therapy than in the inpatient setting (Table). In the outpatient setting, 6 of 17 patients (35%) did not require any hospitalization during the first 2 months post-infusion, whereas 11 of 17 patients (65%) were hospitalized for AEs at a median of 3 days (range 1-25) post-infusion. Patients treated in the inpatient setting had longer total hospitalization days (mean ± SD: 14.3 ± 8.42 vs 5.0 ± 2.16 days) and longer average length of stay (mean ± SD: 13.8 ± 8.54 vs 4.3 ± 1.4 days) compared with the outpatient group. None of the outpatients required ICU admission during the 2 months post-infusion, whereas 7 patients (9%) in the inpatient setting were admitted to the ICU, for a total mean ± SD duration of 5.6 ± 4.47 days (Table). Mean overall hospitalization costs for inpatients were $40,054 per patient, which included $36,351 for inpatient stays and $3,703 for ICU, and $7,477 per patient for outpatients, which are only for inpatient stays as there were no ICU stays. Conclusions: In the ELARA trial, hospitalization and ICU patterns varied substantially between inpatient and outpatient settings and favored HCRU in the outpatient setting. Among patients treated in the outpatient setting, one third of patients did not require hospitalization during the post-infusion period; those who did had a lower average length of stay than the patients infused in an inpatient setting. The mean hospitalization costs in the post-infusion period were substantially lower in the outpatient versus inpatient setting due to the lack of ICU admissions. These data suggest that tisagenlecleucel can be safely administered in the outpatient setting, which may reduce HCRU for patients with r/r FL. Clinical trial information: NCT03568461 Figure 1 Figure 1. Disclosures Fowler: BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company; Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dickinson: Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Chen: Mesolbast: Honoraria; Morphosys: Honoraria. Andreadis: GenMAB: Research Funding; Epizyme: Honoraria; Atara: Consultancy, Honoraria; Crispr Therapeutics: Research Funding; Novartis: Research Funding; BMS/Celgene: Research Funding; Karyopharm: Honoraria; Incyte: Honoraria; Kite: Honoraria; Merck: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; TG Therapeutics: Honoraria. Tiwari: Novartis Healthcare private limited: Current Employment. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Ramos: Novartis: Current Employment, Current equity holder in publicly-traded company. Bollu: Novartis: Current Employment, Current equity holder in publicly-traded company. Jousseaume: Novartis: Current Employment, Current equity holder in publicly-traded company. Thieblemont: Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Dreyling: BeiGene: Consultancy; Astra Zeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Abbvie: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Genmab: Consultancy; Incyte: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau. Schuster: Celgene: Consultancy, Honoraria, Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Abbvie: Consultancy, Research Funding; Acerta Pharma/AstraZeneca: Consultancy; Alimera Sciences: Consultancy; BeiGene: Consultancy; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Tessa Theraputics: Consultancy; Genentech/Roche: Consultancy, Research Funding; Pharmaclyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Merck: Research Funding; Incyte: Research Funding; TG Theraputics: Research Funding; DTRM: Research Funding.

Background: Follicular lymphoma is an indolent disease with a continuous relapsing pattern and typically requires multiple lines of therapy. Novel therapies such as tisagenlecleucel are being investigated to improve outcomes. Primary analysis of the single-arm, multicenter, Phase II ELARA trial in r/r FL demonstrated that tisagenlecleucel resulted in high overall (ORR) and complete response rates (CRR), and prolonged progression-free survival (PFS) at a median follow-up of 11 months (mo). Here, we report updated efficacy results from the overall population at a median follow-up of 17 mo, and a subgroup analysis of pts with high-risk disease from the ELARA trial (NCT03568461). Methods: Eligible adult pts had histologically confirmed r/r FL (grades 1-3A) after ≥2 lines of therapy or had relapsed after autologous stem cell transplant. Bridging therapy was allowed and was followed by disease evaluation before tisagenlecleucel infusion. Pts received tisagenlecleucel (0.6-6×10 8 CAR+ viable T cells) after lymphodepleting chemotherapy (fludarabine [25 mg/m 2] + cyclophosphamide [250 mg/m 2] QD for 3 d or bendamustine [90 mg/m 2] QD for 2 d). Endpoints included ORR, CRR, PFS, and duration of response (DOR). Descriptive efficacy subanalyses were performed for 9 high-risk subgroups, including prior hematopoietic stem cell transplant (HSCT), ≥5 prior lines of therapy, progression of disease within 24 mo from first immunochemotherapy (POD24), double-refractory disease, high Follicular Lymphoma International Prognostic Index (FLIPI) at study entry, high lactate dehydrogenase at baseline, high C-reactive protein (CRP) prior to infusion, radiological bulky disease (by GELF criteria), and high total metabolic tumor volume (TMTV; >510 cm 3) at baseline (median 155.32 cm 3; range 0.1-2470.4 cm 3). Descriptive subgroup analysis was supported by multivariate analysis to identify factors predictive of worse outcomes. Results: As of March 29, 2021, 97 pts received tisagenlecleucel and 94 were evaluable for primary efficacy analysis (median follow-up 17 mo). High and durable responses were seen in the overall ELARA population (ORR 86.2%, CRR 69.1%, 9-mo DOR 76.0%, and 12-mo PFS 67.0%). In CR pts at 9 mo, PFS was 85.5% and estimated probability of remaining in response was 86.5%. Safety reflected known tisagenlecleucel profile; 48% of pts had CRS (majority were grade 1/2) and 11.3% had neurological events (3% grade ≥3). In the subgroup analysis, pts were stratified into risk groups. Efficacy (ORR, CRR) and durability of response were well maintained in all high-risk subgroups, except for POD24 (n=35), high TMTV (n=20), and ≥5 prior lines of therapy (n=27). Compared with corresponding low-risk subgroups, there was a numerical reduction in CRR for high-risk subgroups (POD24 59.0% vs 87.9%; high TMTV 40.0% vs 76.4%; ≥5 prior lines of therapy 59.3% vs 73.1%) (Figure). A reduction in 12-mo PFS was also identified for pts in these subgroups: POD24 (60.8% vs 77.9%), high baseline TMTV (54.5% vs 68.5%), and ≥5 prior lines of therapy (59.6% vs 69.7%). Evaluating the disease characteristics of the high TMTV subgroup compared with low TMTV, high TMTV was associated with a higher incidence of bulky disease (58.3% vs 90.0%), high FLIPI (54.2% vs 85.0%), and high CRP (45.8% vs 70.0%). In the multivariate analysis of high-risk factors, only POD24 (hazard ratio [HR] 2.34; 95% CI, 1.02- 5.34) and high TMTV (HR 2.53; 95% CI, 1.14-5.65) were associated with shorter PFS. For pts with both POD24 and high TMTV (n=12), the CRR was 16.7% with a 12-mo PFS of 36.0%. These analyses of high-risk subgroups are exploratory in nature and should be validated in a larger study cohort. Conclusions : With 17-mo median follow-up, tisagenlecleucel produced high ORR and CRR and was associated with durable response and promising 12-mo PFS in pts with r/r FL and 2+ prior lines of therapy. Safety was consistent with known tisagenlecleucel profile. POD24 and high TMTV were independently associated with PFS. These results suggest that tisagenlecleucel can induce high rates of durable response, including most pts in the high-risk disease subgroups, who have poor prognosis with current non-CAR-T cell therapies. Figure 1 Figure 1. Disclosures Thieblemont: Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Dickinson: Amgen: Honoraria; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Martinez-Lopez: Incyte: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau. Kolstad: Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding. Popplewell: Pfizer: Other: Travel; Novartis: Other: Travel; Hoffman La Roche: Other: Food. Chavez: AstraZeneca: Research Funding; Novartis: Consultancy; MorphoSys: Speakers Bureau; Karyopharm Therapeutics: Consultancy; Adaptive: Research Funding; Kite/Gilead: Consultancy; Abbvie: Consultancy; Merck: Research Funding; BeiGene: Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Speakers Bureau; Epizyme: Speakers Bureau. Bachy: Roche: Consultancy; Takeda: Consultancy; Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Incyte: Consultancy. Kato: Kyowa Kirin: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Research Funding; Dainippon-Sumitomo: Honoraria; Daiichi Sankyo: Consultancy, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding; MSD: Honoraria; Mundi: Honoraria; Novartis: Consultancy, Research Funding; Ono: Honoraria, Research Funding. Harigae: Novartis Pharma: Honoraria, Research Funding; Chugai Pharma: Honoraria; Janssen Pharma: Honoraria; Ono pharma: Honoraria, Other: Subsidies or Donations; Astellas Pharma: Other: Subsidies or Donations; Kyowakirin: Other: Subsidies or Donations; Bristol Myers Squibb: Honoraria. Kersten: Kite/Gilead: Honoraria, Research Funding; Novartis: Honoraria; Miltenyi Biotech: Honoraria; BMS/Celgene: Honoraria, Research Funding; Roche: Honoraria; Takeda: Honoraria. Andreadis: GenMAB: Research Funding; Karyopharm: Honoraria; Incyte: Honoraria; BMS/Celgene: Research Funding; Epizyme: Honoraria; Crispr Therapeutics: Research Funding; Atara: Consultancy, Honoraria; Novartis: Research Funding; Kite: Honoraria; Merck: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; TG Therapeutics: Honoraria. Riedell: Kite/Gilead: Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; BeiGene: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calibr: Research Funding. Pérez-Simón: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Chen: Mesolbast: Honoraria; Morphosys: Honoraria. Nastoupil: MorphoSys: Honoraria; Bayer: Honoraria; Genentech: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Novartis: Honoraria, Research Funding; Gilead/Kite: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Epizyme: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Von Tresckow: Pentixafarm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; MSD: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: Congress and travel support; AstraZeneca: Honoraria, Other: Congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: Congress and travel support; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Ferreri: Gilead, Novartis, Juno, PletixaPharm, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, Pfizer: Research Funding. Teshima: Fuji pharma CO.,Ltd: Research Funding; Astellas Pharma Inc.: Research Funding; TEIJIN PHARMA Limited: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Pfizer Inc.: Honoraria; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Janssen Pharmaceutical K.K.: Other; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol Myers Squibb: Honoraria; Sanofi S.A.: Research Funding; Gentium/Jazz Pharmaceuticals: Consultancy. Patten: ASTRA ZENECA: Honoraria; ABBVIE: Honoraria; NOVARTIS: Honoraria; GILEAD SCIENCES: Honoraria, Research Funding; ROCHE: Research Funding; JANSSEN: Honoraria. McGuirk: Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Novartis: Research Funding; Gamida Cell: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astelllas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Pluristem Therapeutics: Research Funding. Petzer: AppVie: Honoraria; Astra Zeneca: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Sandoz: Honoraria. Viardot: University Hospital of Ulm: Current Employment; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zinzani: JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; SANDOZ: Other: Advisory board; MSD: Consultancy, Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; Incyte: Other, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; ADC Therap.: Other; GILEAD: Other: Advisory board, Speakers Bureau; Beigene: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Malladi: Gilead Science: Consultancy; Gilead: Honoraria, Other: Travel support. Lobetti Bodoni: Spouse: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Spouse: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Spouse: Celgene: Honoraria; Spouse: Harlcok Healthcare: Current holder of individual stocks in a privately-held company; Spouse: Takeda: Consultancy, Honoraria, Speakers Bureau; Spouse: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spouse: NHS: Ended employment in the past 24 months; Spouse: F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company; Gilead: Other: Travel sponsorship in June 2019; Novartis: Current Employment, Current equity holder in publicly-traded company. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Schuster: Genentech/Roche: Consultancy, Research Funding; Tessa Theraputics: Consultancy; Loxo Oncology: Consultancy; BeiGene: Consultancy; Juno Theraputics: Consultancy, Research Funding; Alimera Sciences: Consultancy; Merck: Research Funding; Incyte: Research Funding; Acerta Pharma/AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; TG Theraputics: Research Funding; Pharmacyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Nordic Nanovector: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Dreyling: Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; BeiGene: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Genmab: Consultancy; Amgen: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Abbvie: Research Funding.

Background: Autologous T cells engineered to express a chimeric antigen receptor (CAR) targeting the B-cell lineage antigen CD19 (CAR19) in patients with relapsed/refractory (r/r) aggressive B-cell lymphomas (BCL) and pre-B acute lymphoblastic leukemia (B-ALL) have resulted in transformative improvements in clinical outcomes. However, there remain significant limitations concerning autologous CAR19 T cell manufacturing, including dysfunctional starting material, lack of product consistency and purity following genetic engineering, manufacturing timelines that necessitate the administration of bridging therapy in patients with aggressive disease, and insufficient quantities of CAR19 T cells, especially in severely cytopenic patients, to allow for more than single-dose administration routinely. The ability to consistently administer more than a single dose of CAR19 T cells enables dosing schedules that may reduce the risk of potentially life-threatening toxicities such as cytokine release syndrome and neurotoxicity, while maintaining or improving the depth and durability of anti-tumor responses. FT819 is a first-of-kind, off-the-shelf CAR19 T cell product candidate derived from a clonal master engineered induced pluripotent stem cell (iPSC) line, which can be used as a renewable source for the mass production of off-the-shelf CAR T cells for broad patient access. FT819 is engineered with the following features designed to improve the safety and efficacy of CAR T cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T cell effector function without eliciting exhaustion; integration of the CAR transgene directly into the T cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T cell potency; and complete bi-allelic disruption of T cell receptor (TCR) expression for the prevention of graft-versus-host disease (GVHD). FT819 has demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of donor-derived CAR T cells, and persists and maintains tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Mandal et al. 2020). The properties of FT819 and its ability to improve outcomes of patients with B-cell malignancies warrants further clinical investigation. Study Design and Methods: This study is a multicenter, Phase I clinical trial of FT819 in patients with r/r B-cell malignancies, including BCL, chronic lymphocytic leukemia (CLL), and B-ALL. The primary objective of the trial is to determine the recommended Phase II dose of FT819. Key secondary objectives include evaluation of FT819 safety and tolerability, anti-tumor activity, and pharmacokinetics (PK). Exploratory objectives include characterization of FT819 pharmacodynamics as assessed by peripheral blood biomarkers, and by phenotypic and genetic characterization of the tumor microenvironment from paired pre- and post-treatment tumor biopsies. The dose-escalation part of the trial utilizes a 3+3 dose-escalation design to identify the maximum tolerated dose for BCL, CLL, and B-ALL. The dose-expansion part of the trial is designed to further characterize the safety, efficacy, and PK of FT819 in multiple indications. Up to a maximum of 300 patients will be enrolled. The trial will test up to four FT819 dose levels ranging from 30 to 900 million cells. Three FT819 dosing regimens each will be tested for BCL, CLL, and B-ALL: Regimen A, FT819 administered as a single dose; Regimen A1, FT819 administered as a single dose in combination with interleukin (IL)-2; and Regimen B, FT819 administered as fractionated doses on Days 1, 3, and 5. Lympho-conditioning will consist of three consecutive days of fludarabine and cyclophosphamide administered prior to the first dose of FT819. Key inclusion criteria include r/r disease after standard approved therapies, documented CD19 expression, and adequate organ function. Key exclusion criteria include ongoing immunosuppression such as systemic GVHD therapy, prior allograft organ transplant, active central nervous system involvement of disease, and known allergy to FT819 components. The trial is expected to begin patient recruitment in 2020. Disclosures Park: Novartis: Consultancy; Fate Therapeutics: Research Funding; Amgen: Consultancy, Research Funding; Genentech/Roche: Research Funding; Kite: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; GSK: Consultancy; Autolus: Consultancy, Research Funding; Intellia: Consultancy; Minverva: Consultancy; Takeda: Consultancy, Research Funding; AstraZeneca: Consultancy; Servier: Consultancy, Research Funding; Allogene: Consultancy; Juno Therapeutics: Research Funding; Artiva: Membership on an entity's Board of Directors or advisory committees. Jain:Pfizer: Research Funding; ADC Therapeutics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. McGuirk:Bellicum Pharmaceutical: Research Funding; Gamida Cell: Research Funding; Astellas: Research Funding; Pluristem Ltd: Research Funding; Novartis: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Fresenius Biotech: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding. Diaz:Fate Therapeutics, Inc.: Current Employment. Valamehr:Fate Therapeutics, Inc: Current Employment, Current equity holder in publicly-traded company. Chu:Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company; Roche Holding AG: Current equity holder in publicly-traded company. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding. OffLabel Disclosure: Cyclophosphamide and fludarabine will be used as lympho-conditioning therapy prior to FT819 administration. IL-2 will be administered in order to promote the expansion and function of FT819 as a T-cell product.

INTRODUCTION AND OBJECTIVE:Qualitative methods assessing women’s perspectives on living with OAB have traditionally been obtained via focus groups and interviews. Now a plethora of cyber forums hav...

Summary Background Polatuzumab vedotin, an antibody–drug conjugate targeting the CD79b component of the B-cell receptor, has demonstrated activity as a single agent and in combination with rituximab in relapsed or refractory diffuse large B-cell lymphoma. In this study, we evaluated the safety and preliminary activity of polatuzumab vedotin in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, and prednisone (CHP) in patients with previously untreated diffuse large B-cell lymphoma. Methods This was an open-label, non-randomised study composed of a phase 1b dose escalation and a phase 2 dose expansion at 11 hospitals and health centres in the USA and France. Patients aged 18 years or older with B-cell non-Hodgkin lymphoma were eligible. Exclusion criteria included peripheral neuropathy with grade greater than 1, major surgery within 4 weeks before enrolment, known CNS involvement of lymphoma, and uncontrolled heart disease. Phase 1b dose escalation had a three-plus-three design and established the recommended phase 2 dose. Phase 2 expansion evaluated the recommended phase 2 dose of polatuzumab vedotin in patients with newly diagnosed diffuse large B-cell lymphoma with an International Prognostic Index (IPI) of 2–5. Patients received cyclophosphamide 750 mg/m2 on day 1 intravenously, doxorubicin 50 mg/m2 on day 1 intravenously, and prednisone 100 mg once daily on days 1–5 of each 21-day cycle orally (CHP), plus either rituximab 375 mg/m2 intravenously on day 1 of each cycle (R-CHP) or obinutuzumab 1000 mg intravenously on days 1, 8, and 15 of cycle 1 and on day 1 of the following cycles (G-CHP). Polatuzumab vedotin was administered on day 2 of cycles 1 and 2, and on day 1 of the following cycles at 1·0–2·4 mg/kg during the escalation phase and at the recommended phase 2 dose during the expansion phase. Treatment could last six or eight cycles, depending on investigator preference. The primary endpoints of the study were safety and tolerability, and determination of the maximum tolerated dose (or recommended phase 2 dose) of polatuzumab vedotin. All endpoints were analysed per protocol in the safety evaluable population, defined as all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01992653. Findings Between Dec 4, 2013, and July 26, 2016, 85 patients were enrolled. 82 patients were included in the safety and activity evaluable populations, 25 in phase 1b and 57 in phase 2. In light of information from other studies using polatuzumab vedotin reported during this study, in which the safety profile associated with exposure to polatuzumab vedotin at doses higher than 1·8 mg/kg every 3 weeks was not outweighed by any clinical benefit, the recommended phase 2 dose was set to 1·8 mg/kg in the R-CHP cohort and no higher doses were explored in this study. 66 patients with newly diagnosed diffuse large B-cell lymphoma received the polatuzumab vedotin recommended phase 2 dose (45 R-CHP; 21 G-CHP). In 66 patients with diffuse large B-cell lymphoma who received the recommended phase 2 dose, the most common adverse events of grade 3 or worse were neutropenia (20 [30%]), febrile neutropenia (12 [18%]), and thrombocytopenia (six [9%]). Among the 70 patients (any histology) who received the recommended phase 2 dose, 19 (27%) had grade 1 peripheral neuropathy, eight (11%) grade 2, and two (3%) grade 3. Four deaths were reported during follow-up: two treatment-related (one complication of atrial fibrillation and one septic shock) and two due to disease progression. As of the cutoff date of Dec 29, 2017, median follow-up time was 21·5 months (IQR 16·7–24·3) for the untreated diffuse large B-cell lymphoma cohort treated at the polatuzumab vedotin recommended phase 2 dose. 59 (89%) patients achieved an overall response at end of treatment (51 [77%] patients had a complete response, and eight [12%] patients had a partial response). Interpretation The safety of incorporating polatuzumab vedotin to R-CHP or G-CHP was as expected and managable. Preliminary clinical activity in newly diagnosed diffuse large B-cell lymphoma seems promising and encouraged a phase 3 trial comparing polatuzumab vedotin with R-CHP to R-CHOP. Funding F Hoffmann-La Roche/Genentech.

GDC-0853 is a selective, reversible, and non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) that does not require interaction with the Cys481 residue for activity. In this first-in-human phase 1 study we evaluated safety, tolerability, pharmacokinetics, and activity of GDC-0853 in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Twenty-four patients, enrolled into 3 cohorts, including 6 patients who were positive for the C481S mutation, received GDC-0853 at 100, 200, or 400 mg once daily, orally. There were no dose limiting toxicities. GDC-0853 was well tolerated and the maximum tolerated dose (MTD) was not reached due to premature study closure. Common adverse events (AEs) in ≥ 15% of patients regardless of causality included fatigue (37%), nausea (33%), diarrhea (29%), thrombocytopenia (25%), headache (20%), and abdominal pain, cough, and dizziness (16%, each). Nine serious AEs were reported in 5 patients of whom 2 had fatal outcomes (confirmed H1N1 influenza and influenza pneumonia). A third death was due to progressive disease. Eight of 24 patients responded to GDC-0853: 1 complete response, 4 partial responses, and 3 partial responses with lymphocytosis, including 1 patient with the C481S mutation. Two additional C481S mutation patients had a decrease in size of target tumors (–23% and –44%). These data demonstrate GDC-0853 was generally well-tolerated with antitumor activity.

INTRODUCTION AND OBJECTIVES:Pelvic fracture associated urethral injuries (PFUIs) can cause significant patient morbidity. The management of these patients is complex and can result in lifelong cons...

7532 Background: CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells achieve high response rates in patients (pts) with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL), but are limited by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pivotal trial data suggested distinct toxicity risks across CD19 CAR T-cell products, but differences in pt and disease characteristics may have confounded these observations. Thus, we assessed the independent impact of 3 CD19 CAR T-cell products (axicabtagene ciloleucel[axicel], tisagenlecleucel [tisacel], and JCAR014) on CRS and ICANS severity in 136 pts with R/R aggressive NHL. Methods: We retrospectively analyzed aggressive NHL pts treated at our institutions with cyclophosphamide and fludarabine lymphodepletion (LD) followed by CD19 CAR T-cell therapy. Axicel and tisacel pts were treated off trial using commercial products. JCAR014 (defined-composition 4-1BB-costimulated CD19 CAR T cells) was administered in all pts at the dose of 2x106/kg on a phase I/II clinical trial (NCT01865617). CRS and ICANS were graded according to the ASTCT criteria and CTCAE 4.03, respectively. We used multivariable proportional odds logistic regression to model CRS and ICANS grade. Results: The CAR T-cell product was axicel, tisacel, or JCAR014 in 50%, 28%, and 22% of pts, respectively. Compared to axicel pts, we observed higher preLD LDH levels in tisacel and JCAR014 pts, and lower preLD albumin with tisacel (p < 0.001) with comparable age and hematopoietic cell transplantation comorbidity (HCT-CI) indexes across CAR T-cell products. Higher day-28 overall response rate by Lugano criteria was observed after axicel (71%) compared to tisacel (56%) and JCAR014 (53%). Adjusting for age, HCT-CI, preLD LDH, preLD albumin, CAR T-cell product type was associated with CRS severity (tisacel versus [vs] axicel, OR = 0.45, p = 0.05; JCAR014 vs axicel, OR = 0.29, p = 0.005;). Age had limited or no impact on CRS severity (OR 95%CI, 0.97-1.02), while the effect of HCT-CI was undetermined (OR 95%CI, 0.85-1.27). In a multivariable model including the same covariates as above, CAR T-cell product type (tisacel vs axicel, OR =.14, p

Purpose: Pinatuzumab vedotin is an antibody–drug conjugate with the potent antimicrotubule agent monomethyl auristatin E (MMAE) conjugated to an anti-CD22 antibody via a protease-cleavable linker. This phase I study determined its recommended phase II dose (RP2D) and evaluated its safety, tolerability, and antitumor activity alone and with rituximab in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Experimental Design: Patients received escalating doses of pinatuzumab vedotin every 21 days. Clinical activity at the RP2D alone or with rituximab was evaluated in r/r diffuse large B-cell lymphoma (DLBCL) and r/r indolent NHL (iNHL) patients. Results: Seventy-five patients received single-agent pinatuzumab vedotin. The RP2D was 2.4 mg/kg, based on dose-limiting toxicities (DLT) of grade 4 neutropenia >7 days in 1 of 3 patients and grade 4 neutropenia Conclusions: The RP2D of pinatuzumab vedotin alone and with rituximab was 2.4 mg/kg, which was well tolerated, with encouraging clinical activity in r/r NHL. Clin Cancer Res; 23(5); 1167–76. ©2016 AACR.

Summary Brentuximab vedotin (BV) significantly improved progression-free survival in a phase 3 study in patients with relapsed or refractory Hodgkin lymphoma (RR-HL) post-autologous-haematopoietic stem cell transplant (auto-HSCT); we report the impact of BV on quality of life (QOL) from this trial. The European Quality of Life five dimensions questionnaire was administered at the beginning of each cycle, end of treatment, and every 3 months during follow-up; index value scores were calculated using the time trade-off (TTO) method for UK-weighted value sets. Questionnaire adherence during the trial was 87·5% (N = 329). In an intent-to-treat analysis, compared with placebo, TTO scores in the BV arm did not exceed the minimally important difference (MID) of 0·08 except at month 15 (−0·084; 95% confidence interval, −0·143 to −0·025). On-treatment index scores were similar between arms and did not reach the MID at any time point; mixed-effect modelling showed that BV treatment effect was not significant (P = 0·2127). BV-associated peripheral neuropathy did not meaningfully impact QOL. Utility scores for patients who progressed declined compared with those who did not; TTO scores between these patients exceeded the MID beginning at month 15. In conclusion, QOL decreased modestly with BV consolidation treatment in patients with RR-HL at high risk of relapse after auto-HSCT.

Summary Background Antibody–drug conjugates (ADCs) polatuzumab vedotin (pola) and pinatuzumab vedotin (pina) showed clinical activity and tolerability in phase 1 trials. The aim of this multicentre, open-label, phase 2 study was to compare rituximab plus pola (R-pola) or pina (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Methods In this phase 2 randomised study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomisation scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs) every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumour response. The study is registered with ClinicalTrials.gov , number NCT01691898 , and is closed to accrual. Findings 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI 43–74) achieved an objective response and 11 (26%, 95% CI 14–42) achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI 37–70) achieved an objective response, and eight (21%, 95% CI 9–36) achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI 38–82) achieved an objective response, and one (5%, 95% CI 0·1–24) achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI 46–88) achieved an objective response, and nine (45%, 95% CI 23–68) achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3–5 adverse events occurred in 33 (79%) of 42 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [10%]; nine [21%] grade 5 adverse events, five of which were infection-related), and in 30 (77%) of 39 patients receiving R-pola (most common were neutropenia [23%], anaemia [8%] and diarrhoea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3–5 adverse events occurred in 13 (62%) of 21 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [14%]; no grade 5 adverse events) and in ten (50%) of 20 patients receiving R-pola (most common were neutropenia [15%] and diarrhoea [10%]; one grade 5 adverse event). Interpretation R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit–risk favouring R-pola. Funding F Hoffmann-La Roche.

High-dose therapy followed by autologous stem-cell transplantation is standard of care for patients with relapsed or primary refractory Hodgkin's lymphoma. Roughly 50% of patients might be cured after autologous stem-cell transplantation; however, most patients with unfavourable risk factors progress after transplantation. We aimed to assess whether brentuximab vedotin improves progression-free survival when given as early consolidation after autologous stem-cell transplantation.We did this randomised, double-blind, placebo-controlled, phase 3 trial at 78 sites in North America and Europe. Patients with unfavourable-risk relapsed or primary refractory classic Hodgkin's lymphoma who had undergone autologous stem-cell transplantation were randomly assigned, by fixed-block randomisation with a computer-generated random number sequence, to receive 16 cycles of 1·8 mg/kg brentuximab vedotin or placebo intravenously every 3 weeks, starting 30-45 days after transplantation. Randomisation was stratified by best clinical response after completion of salvage chemotherapy (complete response vs partial response vs stable disease) and primary refractory Hodgkin's lymphoma versus relapsed disease less than 12 months after completion of frontline therapy versus relapse 12 months or more after treatment completion. Patients and study investigators were masked to treatment assignment. The primary endpoint was progression-free survival by independent review, defined as the time from randomisation to the first documentation of tumour progression or death. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01100502.Between April 6, 2010, and Sept 21, 2012, we randomly assigned 329 patients to the brentuximab vedotin group (n=165) or the placebo group (n=164). Progression-free survival by independent review was significantly improved in patients in the brentuximab vedotin group compared with those in the placebo group (hazard ratio [HR] 0·57, 95% CI 0·40-0·81; p=0·0013). Median progression-free survival by independent review was 42·9 months (95% CI 30·4-42·9) for patients in the brentuximab vedotin group compared with 24·1 months (11·5-not estimable) for those in the placebo group. We recorded consistent benefit (HR1) of brentuximab vedotin consolidation across subgroups. The most frequent adverse events in the brentuximab vedotin group were peripheral sensory neuropathy (94 [56%] of 167 patients vs 25 [16%] of 160 patients in the placebo group) and neutropenia (58 [35%] vs 19 [12%] patients). At time of analysis, 28 (17%) of 167 patients had died in the brentuximab vedotin group compared with 25 (16%) of 160 patients in the placebo group.Early consolidation with brentuximab vedotin after autologous stem-cell transplantation improved progression-free survival in patients with Hodgkin's lymphoma with risk factors for relapse or progression after transplantation. This treatment provides an important therapeutic option for patients undergoing autologous stem-cell transplantation.Seattle Genetics and Takeda Pharmaceuticals International.

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM).Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P .0001).Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society.

GDC-0853 is a selective, reversible, and non-covalent inhibitor of Bruton's tyrosine kinase (BTK) that does not require interaction with the Cys481 residue for activity. In this first-in-human phase 1 study we evaluated safety, tolerability, pharmacokinetics, and activity of GDC-0853 in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Twenty-four patients, enrolled into 3 cohorts, including 6 patients who were positive for the C481S mutation, received GDC-0853 at 100, 200, or 400 mg once daily, orally. There were no dose limiting toxicities. GDC-0853 was well tolerated and the maximum tolerated dose (MTD) was not reached due to premature study closure. Common adverse events (AEs) in ≥ 15% of patients regardless of causality included fatigue (37%), nausea (33%), diarrhea (29%), thrombocytopenia (25%), headache (20%), and abdominal pain, cough, and dizziness (16%, each). Nine serious AEs were reported in 5 patients of whom 2 had fatal outcomes (confirmed H1N1 influenza and influenza pneumonia). A third death was due to progressive disease. Eight of 24 patients responded to GDC-0853: 1 complete response, 4 partial responses, and 3 partial responses with lymphocytosis, including 1 patient with the C481S mutation. Two additional C481S mutation patients had a decrease in size of target tumors (-23% and -44%). These data demonstrate GDC-0853 was generally well-tolerated with antitumor activity.

Objectives: B-cell prolymphocytic leukemia (B-PLL) remains a controversial entity, and its molecular pathogenesis is largely unknown. Patients are older, typically having marked lymphocytosis and splenomegaly in the absence of lymphadenopathy. It is defined as a mature B-cell leukemia with more than 55% circulating prolymphocytes. Leukemic mantle cell lymphoma and chronic lymphocytic leukemia in prolymphocytic transformation must be excluded. Methods: Case archives were retrospectively reviewed for B-PLL in patients without a previous diagnosis of chronic lymphocytic leukemia or other B-cell neoplasm. Results: We identified six cases of B-PLL with available cytogenetic data, five of which showed evidence of aberrations in MYC . Three cases showed additional signals for the MYC gene by fluorescence in situ hybridization (FISH), and two cases demonstrated t(8;14) MYC/IGH by karyotyping or FISH. High levels of MYC protein expression were detected in all cases tested with MYC aberrations. Conclusions: These results suggest that deregulation of MYC plays an important role in the pathogenesis of B-PLL and expands the spectrum of B-cell neoplasms associated with aberrations of MYC .

Background: Very elderly patients (75 years and older) with diffuse large B-cell lymphoma (DLBCL) will be increasingly considered for cancer treatment as the population ages, but are underrepresented in clinical trials. Here we report outcomes of very elderly DLBCL patients treated in the modern era at the Oregon Health and Science University (OHSU). Methods: We queried the OHSU Tumor Registry for DLBCL cases treated since 2002. A total of 73 patients aged 75 years or older were analyzed under Institutional Review Board approval. Results: With a median follow up of 31 months, cause-specific survival was 58% and overall survival 51% at 3 years. Incorporation of an anthracycline did not influence outcomes. More than one extranodal site or poor-risk disease by Revised International Prognostic Index score were adversely prognostic, but pathologic features studied were not. Conclusions: Very elderly patients with DLBCL require prospective studies, which employ novel risk stratification and therapeutic approaches.

For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30%, 38%, 31% and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS)

Robert Chen,1 Suzanne Allibone,2 Nancy L Bartlett,3 Pauline Brice,4 Andy Chen,5 Katrina Pose,6 Lynn Rich,7 Vijay Bonthapally,8 Phillip M Garfin,9 Michelle Fanale10 1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA; 2The Lymphoma Service of the Christie NHS Foundation Trust, Manchester, UK; 3Department of Medical Oncology, Washington University School of Medicine, St Louis, MO, USA; 4Department of Hemato-Oncology, Hôpital Saint-Louis, Paris, France; 5Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 6Lymphoma and Cancer Survivorship Stanford Comprehensive Cancer Center, Stanford, CA, 7Lymphoma Program, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, 8Millennium Pharmaceuticals Inc., Cambridge, MA, 9Seattle Genetics, Inc., Bothell, WA, 10Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: Patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or R/R systemic anaplastic large-cell lymphoma (sALCL) treated with brentuximab vedotin (BV) experienced high remission rates in two Phase II trials. With increased response rates and survival times, patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are becoming increasingly important and can help inform treatment decisions to enhance care of cancer patients.Objective: The objective was to qualitatively assess HRQoL in long-term survivors treated with BV.Methods: An eight-question survey assessing PRO-related aspects was developed and fielded to a subset of patients with HL or sALCL who remained in long-term follow-up after completing BV treatment in the two pivotal studies.Results: The survey was completed by 25 of 38 patients (12 with HL, 13 with sALCL). The majority of patients reported that their energy level, outlook on life, difficulties with daily activities, ability to participate in physical activities, and overall HRQoL improved compared to those before BV treatment.Limitations: Small sample size and lack of a baseline questionnaire or validated assessment instrument limit broad applicability of these findings to large populations of patients with HL or sALCL.Conclusion: This is the first report of BV PRO data in R/R HL and sALCL. Given the patients’ poor prognostic outcomes before stem cell transplant, these encouraging results warrant formal evaluation of PRO end points in BV trials. Keywords: patient well-being, brentuximab vedotin, health-related quality of life, pilot study, activities of daily living

Single autologous hematopoietic cell transplant (AHCT) with high-dose melphalan prolongs survival in patients with multiple myeloma but is not curative. We conducted a study of intensive single AHCT using tandem chemomobilization with CY and etoposide followed by high-dose conditioning with melphalan 200 mg/m2 plus carmustine 15 mg/kg. One hundred and eighteen patients in first consolidation (CON1) and 58 patients in relapse (REL) were transplanted using this intensified approach. Disease response improved from 32% very good PR (VGPR) + CR pre-mobilization to 76% VGPR + CR post transplant in CON1. With a median follow-up of 4.7 years, the median EFS was 2.8 years, and the median OS was 5.1 years in CON1. OS from time of transplant was significantly shorter for REL (3.4 years) compared with CON1 (5.1 years; P = 0.02). However, OS from time of diagnosis was similar in REL (6.1 years) and CON1 (6.0 years; P = 0.80). The 100-day non-relapse mortality in the CON1 and REL groups was 0% and 7%, respectively. In summary, intensified single AHCT with tandem chemo-mobilization and augmented high-dose therapy is feasible in multiple myeloma and leads to high-quality response rates.

The management of chemotherapy-induced nausea and vomiting (CINV) during preparative regimens for Hematopoietic Stem Cell Transplant (HSCT) continues to be a poorly studied area and an unmet patient need. The primary aim of this study was to assess the efficacy of NEPA to prevent N/V both during and after HSCT conditioning. NEPA is a recently approved combination antiemetic, containing fixed doses of netupitant and palonosetron. Nausea, emesis, and nutritional intake, were evaluated from the start of conditioning through day 4 post-transplant. NEPA was administered Days 1, 3 and 6 of conditioning, dexamethasone (Days 1-6) and BEAM (Carmustine (300 mg/m2 D1), Etoposide/Cytarabine (200/400 mg/m2 D2-5), Melphalan (140 mg/m2 D 6)) preparative regimen (Days 1-6) in 17 patients. Patient nausea and emesis was self-reported using daily assessments and rescue therapy was determined using chart review. Two out of 17 patients experienced emesis (11.7%) after all chemotherapy was completed with no emesis in any patient during chemotherapy. During the observation period, 6 patients did not receive rescue medications (35%) and time to first rescue in other patients was a mean of 188.9 hours from the start of chemotherapy (median 172.4, SD 89 hrs). Responses were classified as either complete (CR) or major (MR), with CR defined as: no emesis, mild-moderate nausea for hours 0-264 (6 days of chemotherapy and 5 days post-chemotherapy), and (MR) defined as: 1-2 emesis on only 1 day with any level nausea or no emesis with severe nausea. Five out of 16 patients reported CR (31%) and 11 reported a major response (69%) at their end of treatment (EOT) visit. One patient did not participate in the EOT visit. The patient population in this study was 47% female, 100% Caucasian, the average age was 62 years old and the following diagnoses were included: Peripheral T-cell Lymphoma (24%), Hodgkin lymphoma (23%), mantle cell lymphoma (29%), and Diffuse large B-cell lymphoma (24%). The following expected adverse events were reported amongst 17 treated patients: anemia (82%); neutropenia (65%); lymphocyte decrease (94%); decreased neutrophils (94%); white blood cell decrease (88%); abdominal pain (59%); constipation (53%); diarrhea (59%); abdominal cramping (35%); nausea (82% all grades); bacteremia (29%); hypophosphatemia (24%); and hypokalemia (29%). Constipation was deemed possibly related to NEPA; additional reported adverse events were not related to study drug. In this interim analysis, NEPA plus dexamethasone was effective in preventing emesis with BEAM conditioning with no increase in adverse events prior to HSCT.