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B-cell maturation antigen (BCMA)–targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADCs), are promising treatments for multiple myeloma (MM), but disease may progress after their use. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel, an anti-BCMA chimeric antigen receptor T therapy, in various myeloma patient populations. Patients in cohort C progressed despite treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and noncellular anti-BCMA immunotherapy. A single cilta-cel infusion was given after lymphodepletion. The primary end point was minimal residual disease (MRD) negativity at 10−5. Overall, 20 patients were treated (13 ADC exposed; 7 BsAb exposed; 1 in the ADC group also had prior BsAb exposure). Sixteen (80%) were refractory to prior anti-BCMA therapy. At a median follow-up of 11.3 months (range, 0.6-16.0), 7 of 20 (35%) patients were MRD negative (7 of 10 [70.0%] in the MRD-evaluable subset). Overall response rate (95% confidence interval [CI]) was 60.0% (36.1-80.9). Median duration of response and progression-free survival (95% CI) were 11.5 (7.9—not estimable) and 9.1 (1.5—not estimable) months, respectively. The most common adverse events were hematologic. Cytokine release syndrome occurred in 12 (60%) patients (all grade 1-2); 4 had immune effector cell-associated neurotoxicity syndrome (2 had grade 3-4); none had parkinsonism. Seven (35%) patients died (3 of progressive disease, 4 of adverse events [1 treatment related, 3 unrelated]). Cilta-cel induced favorable responses in patients with relapsed/refractory MM and prior exposure to anti-BCMA treatment who had exhausted other therapies. This trial was registered at www.clinicaltrials.gov as NCT04133636.

B-cell maturation antigen (BCMA)-targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADC), are promising treatments for multiple myeloma (MM), but disease may progress after their use. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel, an anti-BCMA chimeric antigen receptor T therapy, in various myeloma patient populations. Patients in cohort C progressed despite treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non‑cellular anti-BCMA immunotherapy. A single cilta-cel infusion was given after lymphodepletion. The primary end point was minimal residual disease (MRD) negativity at 10-5. Overall, 20 patients were treated (13 ADC-exposed; 7 BsAb-exposed; 1 in the ADC group also had prior BsAb exposure); 16 (80%) were refractory to prior anti-BCMA therapy. At a median follow-up of 11.3 months (range, 0.6-16.0), 7/20 (35%) patients were MRD-negative (7/10 [70.0%] in the MRD-evaluable subset). Overall response rate (95% CI) was 60.0% (36.1-80.9). Median duration of response and progression-free survival (95% CI) were 11.5 (7.9-not estimable) and 9.1 (1.5-not estimable) months, respectively. The most common adverse events were hematologic. Cytokine release syndrome occurred in 12 (60%) patients (all grade 1/2); 4 had immune effector cell-associated neurotoxicity syndrome (2 grade 3/4); none had parkinsonism. Seven (35%) patients died (3 of progressive disease, 4 of adverse events [1 treatment-related, 3 unrelated]). Cilta-cel induced favorable responses in patients with relapsed/refractory MM and prior exposure to anti-BCMA treatment who have exhausted other therapies. This trial was registered at www.clinicaltrials.gov as #NCT04133636.

Objective Cilta-cel (JNJ-68284528) is a chimeric antigen receptor T cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficacy and safety of cilta-cel in patients with multiple myeloma (MM) in various clinical settings. We describe the mitigation and management strategies implemented to identify and reduce the risk for neurologic adverse events in patients enrolled in Cohort A (progressive MM after 1-3 prior lines of therapy). Method and materials Eligible patients (≥18 years of age) had MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive disease after 1-3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory drug), were lenalidomide refractory, and had not received BCMA-targeting agents. Cilta-cel (0.75 × 106 [range 0.5– 1.0 × 106] CAR+ viable T cells/kg) was given as a single infusion 5–7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). Monitoring and mitigation strategies for neurologic adverse events include providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T related immune effector cellassociated neurotoxicity syndrome (ICANS) using the immune effector cellassociated encephalopathy tool, regular handwriting assessments to detect micrographia, and neuroimaging (brain MRI) and electroencephalogram for patients with prior neurologic disease. Management strategies include evaluating infectious and paraneoplastic etiologies upon observation of ICANS ≥grade 1, administration of tocilizumab (if concurrent with cytokine release syndrome [CRS], all grade of ICANS) and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). ICANS and CRS were graded by American Society for Transplantation and Cellular Therapy criteria; neurotoxicities not classified as ICANS were graded per common terminology criteria for adverse events, v5.0. Results As of 15 Jan 2021 (median follow-up: 5.8 months [range: 2.5–9.8]), 20 patients in Cohort A received cilta-cel. Median age was 60 years (range: 38–75) and 65% were male. Neurotoxicities occurred in 4 patients (20%). Three patients had ICANS (grade 1/2); median time to onset of symptoms was 8 days (range: 7–11) and median duration was 2 days (range: 1–2). Two of the 3 patients received supportive measures to treat ICANS, including levetiracetam and steroids; all 3 had concurrent CRS and all recovered. One patient developed isolated facial paralysis (grade 2) on Day 29 after cilta-cel infusion and recovered 51 days after onset following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported. Discussion Early detection and management of neurologic adverse events can lead to better treatment outcomes. Conclusion Neurologic adverse events were generally manageable in patients with MM following treatment with cilta-cel. With a median of 5.8 months of follow-up, there were no movement or neurocognitive disorders in patients from Cohort A.

Objectives: Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma. Material and methods: Patients enrolled in Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and were naïve to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75 × 106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE; CRS and ICANS by ASTCT). Results: As of the February 2021 data cutoff (median follow-up: 5.8 months [2.5–9.8]), 20 patients (65% male; median age 60 years [38–75]) received cilta-cel; 1 patient was treated in an outpatient setting. Patients (n = 12

8020 Background: Cohort A of the multicohort phase 2 CARTITUDE-2 (NCT04133636) study is evaluating cilta-cel safety and efficacy in pts with MM who received 1–3 prior LOT and were len-refractory – a difficult-to-treat population with poor prognosis. We present updated results. Methods: Pts had progressive MM after 1–3 prior LOT, including a PI and IMiD, were len-refractory, and had no prior exposure to BCMA-targeting agents. A single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) was given post lymphodepletion. Safety and efficacy were assessed, and the primary endpoint was MRD negativity at 10-5. Management strategies were implemented to minimize risk of movement/neurocognitive AEs (MNTs). Pharmacokinetic (PK) analyses (Cmax and Tmax of CAR+ T-cell transgene levels in blood) are being conducted, as well as analyses of levels of CRS-related cytokines (eg, IL-6) over time, peak levels of cytokines by response and CRS, association of cytokine levels with ICANS, and CAR+ T cell CD4/CD8 ratio by response, CRS, and ICANS. Results: As of January 2022 (median follow-up [MFU] 17.1 mo [range 3.3–23.1]), 20 pts (65% male; median age 60 y [range 38–75]) received cilta-cel. Pts received a median of 2 (range 1–3) prior LOT, and a median of 3.5 y (range 0.7–8.0) since MM diagnosis. 95% were refractory to last LOT, and 40% were triple-class refractory. ORR was 95%, 90% achieved CR or better, and 95% had ≥VGPR. Median times to first and best response were 1.0 mo (range 0.7–3.3) and 2.6 mo (range 0.9–13.6), respectively. 16 pts were MRD-evaluable, all of whom achieved MRD negativity at 10-5. Median DOR was not reached and 12-mo event-free rate was 79%. The 12-mo PFS rate was 75%. Median time to onset of CRS was 7 d (range 5–9) and occurred in 95% of pts (gr 3/4: 10%), with median duration of 3 d (range 2–12). Neurotoxicity occurred in 30% of pts (5 gr 1/2; 1 gr 3/4). 3 pts (15%) had ICANS (all gr 1/2); 1 pt had gr 2 facial paralysis. No MNTs were seen. 1 death occurred due to COVID-19 (assessed as tx-related by the investigator), 2 due to progressive disease, and 1 due to sepsis (not related to tx). Preliminary PK analyses indicate that peak expansion of CAR-T cells occurred at d 10.5 (range 8.7–42.9) and median persistence was 153.5 d (range 57.1–336.8). Conclusions: At a longer MFU of 17.1 mo, a single cilta-cel infusion led to deepening and durable responses in pts with MM who had 1–3 prior LOT and were len-refractory. Follow-up is ongoing. Updated and in-depth PK, cytokine, and CAR-T subset analyses and clinical correlation will be presented and provide novel insights into biological correlates of efficacy and safety in this pt population. This pt population is being further evaluated in the CARTITUDE-4 study (NCT04181827), which has concluded enrollment. Clinical trial information: NCT04133636.

8029 Background: In cohort B of the multicohort phase 2 CARTITUDE-2 (NCT04133636) study, the efficacy and safety of cilta-cel are being evaluated in patients (pts) with MM who had early relapse after initial therapy. These pts have functionally high-risk disease, with early relapse post autologous stem cell transplantation (ASCT) being a poor prognostic factor and representing an unmet medical need. We present updated results. Methods: Eligible pts had MM, received 1 prior LOT (PI and IMiD required), had disease progression per IMWG (either ≤12 mo after ASCT or ≤12 mo after start of anti-myeloma therapy for pts who did not undergo ASCT), and were tx-naive to CAR-T/anti-BCMA therapies. A single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) was given post lymphodepletion. Safety and efficacy were assessed, and the primary endpoint was MRD negativity at 10-5. Management strategies were implemented to minimize risk of movement/neurocognitive AEs (MNTs). Pharmacokinetic (PK) analyses (Cmax and Tmax of CAR+ T-cell transgene levels in blood) are being conducted, as well as analyses of levels of CRS-related cytokines (eg, IL-6) over time, peak levels of cytokines by response and CRS, association of cytokine levels with ICANS, and CAR+ T cell CD4/CD8 ratio by response, CRS, and ICANS. Results: As of January 2022, 19 pts (median age 58.0 y [range 44–67]; 74% male; median follow-up 13.4 mo [range 5.2–21.7]) received cilta-cel. 79% of pts received prior ASCT. ORR was 100.0%, 90% achieved CR or better, and 95% achieved ≥VGPR. Median time to first response and best response were 0.95 mo (range 0.9–9.7) and 5.1 mo (range 0.9–11.8), respectively. Of pts who were MRD-evaluable (n = 15), 14 (93%) achieved MRD 10-5 negativity during this study. Median DOR was not reached and 12-mo event-free rate was 88.9%. The 12-mo PFS rate was 90%. Median time to onset of CRS was 8 d (range 5–11) and occurred in 16 (84.2%) pts (1 gr 4). CRS resolved in all pts. ICANS (gr 1) occurred in 1 pt; MNT (gr 3) occurred in 1 pt, previously reported. 1 pt died post cilta-cel due to PD at d 158. Preliminary PK analyses indicate that peak expansion of CAR-T cells occurred on d 13.1 (range 8.96–209.9) and median persistence was 76.9 d (range 40.99–221.8). Conclusions: A single cilta-cel infusion led to deep and durable responses in a functionally high-risk pt population who experienced early clinical relapse/tx failure to initial therapy, with a manageable safety profile. In this pt population with ineffective or insufficient response to ASCT, cilta-cel led to responses. Responses continue to deepen, and follow-up is ongoing. Updated and in-depth PK, cytokine, and CAR-T subset analyses and clinical correlation will be presented and provide novel insights into biological correlates of efficacy and safety in this pt population. Clinical trial information: NCT04133636.

Background CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficacy and safety of cilta-cel, a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen (BCMA)-targeting single-domain antibodies, in patients (pts) with multiple myeloma (MM) in various clinical settings. This report describes the mitigation and management strategies implemented to identify and reduce the risk for neurologic adverse events (AEs) in pts with progressive MM after 1–3 prior lines of therapy (Cohort A). Methods Eligible pts (≥18 years) had MM, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive disease after 1–3 prior lines of therapy including a proteasome inhibitor and immunomodulatory drug, and were lenalidomide refractory (no prior BCMA-targeting agent). Cilta-cel was given as a single infusion at the targeted dose of 0.75×106 (range 0.5–1.0×106) CAR+ viable T cells/kg 5–7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). Monitoring and mitigation strategies for neurologic AEs included providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T-related immune effector cell-associated neurotoxicity syndrome (ICANS) using the ICE tool, handwriting assessments to detect micrographia, and brain MRI and electroencephalogram for pts with prior neurologic disease. Management strategies included evaluating infectious and paraneoplastic etiologies upon observation of ICANS ≥grade 1, administration of tocilizumab (if concurrent with cytokine release syndrome [CRS], all grades of ICANS) and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). ICANS and CRS were graded by American Society for Transplantation and Cellular Therapy criteria; non-ICANS neurotoxicities were graded per Common Terminology Criteria for Adverse Events, v5.0. Results As of 15 Jan 2021 (median follow-up: 5.8 months [2.5–9.8]), 20 pts (65% male, median age 60 years [38–75]) in Cohort A received cilta-cel. Four pts (20%) had neurotoxicities. Three pts had ICANS (grade 1/2) with median time to onset of symptoms of 8 days (7–11) and median duration of 2 days (1–2). Supportive measures to treat ICANS were received by 2/3 pts, including levetiracetam and steroids; 3/3 had concurrent CRS and all recovered. One pt developed isolated facial paralysis (grade 2); onset: Day 29 after cilta-cel infusion, recovered: 51 days after the onset following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported. Conclusion In pts with MM, neurologic AEs were generally manageable following treatment with cilta-cel. With a median of 5.8 months of follow-up, no movement or neurocognitive disorders were reported in pts from Cohort A. These findings suggest that early detection and management of neurologic AEs can lead to better treatment outcomes.

Context Cilta-cel, a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen (BCMA)-targeting single-domain antibodies demonstrated efficacy in relapsed/refractory multiple myeloma (MM). Objectives To describe mitigation and management strategies to identify and reduce the risk for neurologic adverse events (AEs). Design CARTITUDE-2 (NCT04133636) is an ongoing phase 2, multi-cohort, open-label study. Patients and Other Participants Patients had progressive MM per IMWG criteria, measurable disease, ECOG ≤1, received 1–3 prior lines of therapy (including PI and IMiD), and were lenalidomide refractory (no prior BCMA-targeting agent). Interventions Cilta-cel (target dose: 0.75×106 [0.5–1.0×106] CAR+ viable T cells/kg) was given as a single infusion after lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2). Monitoring and mitigation of neurologic AEs included effective bridging therapy to reduce tumor burden prior to lymphodepletion, assessment of CAR-T-related immune effector cell-associated neurotoxicity syndrome (ICANS) using an ICE tool, handwriting assessments, and neuroimaging and electroencephalogram for prior neurologic disease patients. Management of neurologic AEs included evaluating infectious and paraneoplastic etiologies with ICANS ≥grade 1, administration of tocilizumab (if concurrent CRS, all grades of ICANS), and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). Main Outcomes Measures ICANS and CRS were graded by ASTCT criteria; non-ICANS neurotoxicities were graded per CTCAE v5.0. Results As of 15 Jan 2021 (median follow-up: 5.8 months), 20 patients in Cohort A (median age: 60 years; 65% males) received cilta-cel. Four patients (20%) had neurotoxicities. Three patients had ICANS (grade 1/2); median time to onset of symptoms: 8 days (7–11) and median duration: 2 days (1–2). Supportive measures, including levetiracetam and steroids, were received by 2/3 patients; all 3 had concurrent CRS and all recovered. One patient developed isolated facial paralysis (grade 2; onset: Day 29 after cilta-cel infusion; recovery: 51 days after the onset; treatment: dexamethasone for 28 days). Conclusions Neurologic AEs were generally manageable in patients with MM following cilta-cel treatment. No movement or neurocognitive disorders were observed in patients from Cohort A. Early detection and management of neurologic AEs can lead to better treatment outcomes Acknowledgements The study was funded by Janssen Research & Development, LLC and Legend Biotech, Inc.

PURPOSE Patients with lower-risk (LR) myelodysplastic syndromes (MDS) who are RBC transfusion dependent and have experienced relapse after or are refractory to erythropoiesis-stimulating agent (ESA) have limited treatment options. High telomerase activity and human telomerase reverse-transcription expression in clonal hematopoietic cells have been reported in patients with MDS. Imetelstat, a first-in-class competitive inhibitor of telomerase enzymatic activity, targets cells with active telomerase. We report efficacy, safety, and biomarker data for patients with LR MDS who are RBC transfusion dependent and who were relapsed/refractory to ESAs. PATIENTS AND METHODS In this two-part phase II/III study (MDS3001), the primary end point was 8-week RBC transfusion independence (TI) rate, with key secondary end points of 24-week RBC TI rate, TI duration, and hematologic improvement-erythroid. RESULTS Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks. CONCLUSION Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.

Introduction: There are several treatment options for patients (pts) with progressive multiple myeloma (MM) who are refractory to lenalidomide but most pts relapse shortly after receiving salvage treatment. Cilta-cel is a CAR-T therapy expressing 2 BCMA-targeting, single-domain antibodies that demonstrated early, deep, and durable responses in pts with MM who had received ≥3 prior lines of therapy (LOT) in the phase 1b/2 CARTITUDE-1 study (Berdeja, Lancet, 2021). The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for pts with MM and exploring suitability of outpatient administration. Initial analysis (median follow-up 5.8 mo) of pts in CARTITUDE-2 cohort A (lenalidomide-refractory with 1-3 prior LOT) demonstrated an overall response rate (ORR) of 95%, with 75% of pts achieving complete response or better (≥CR) and 85% achieving very good partial response or better (≥VGPR). Here, we present updated results for this population. Methods: Pts had progressive MM after 1-3 prior LOT, including a PI and immunomodulatory drug (IMiD), were lenalidomide-refractory, and had no prior exposure to BCMA-targeting agents. Bridging therapy was allowed after apheresis. A single cilta-cel infusion (target dose 0.75×10 6 CAR+ viable T cells/kg) was given 5-7 d after start of lymphodepletion (daily cyclophosphamide [300 mg/m 2] and fludarabine [30 mg/m 2] for 3 d). The primary endpoint was minimal residual disease (MRD) negativity at 10 -5. Secondary endpoints were ORR, duration of response (DOR), time and duration of MRD negativity, and incidence and severity of AEs. MRD was assessed by next-generation sequencing, response was assessed per IMWG criteria, and adverse events (AEs) were graded using CTCAEv5.0 (CRS and ICANS by ASTCT). Results: Initial results from this cohort were published at ASCO 2021 . Here we report data as of the April 15, 2021, data cutoff (median follow-up 9.7 mo: range 3.3-13.4) . 20 pts (65% male; median age 60 years [range 38-75]) received cilta-cel; 1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (range 1-3); 60% received 1 or 2 prior LOT and 40% received 3 prior LOT. All pts were exposed to a PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. In all, 95% of pts were refractory to the last LOT; 40% were triple-class refractory. ORR was 95% (95% CI 75.1-99.9); 85% (95% CI 62.1-96.8) of pts had ≥CR, and 95% (95% CI 75.1-99.9) had ≥VGPR (Figure). Median time to first response was 1.0 mo (range 0.7-3.3); median time to best response was 3.3 mo (range 0.9-7.9); median time to ≥CR was 2.6 mo (range 0.9-7.9). Median DOR was not reached; 6-mo PFS rate was 90% (95% CI 65.6-97.4). Of MRD-evaluable pts (n=13), 92.3% (95% CI 64.0-99.8) were MRD-negative at 10 -5. Hematologic AEs in ≥20% of pts were neutropenia (95%; grade [gr] 3/4: 95%), thrombocytopenia (80%; gr 3/4: 35%), anemia (75%; gr 3/4: 45%), lymphopenia (65%; gr 3/4: 60%) and leukopenia (55%; gr 3/4: 55%). CRS occurred in 95% of pts (gr 3/4: 10%). Median time to CRS onset was 7 d (range 5-9), with a median duration of 4 d (range 2-11). CRS resolved within 7 d in 90% of pts. CAR T-cell neurotoxicity occurred in 4 pts (20%; all gr 1/2). Three pts (15%) had ICANS (all gr 1/2); median time to onset was 8 d (range 7-10) and median duration was 3 d (range 1-3). One pt had other neurotoxicities (gr 2 facial paralysis); time to onset was 29 d with a duration of 51 d. No movement and neurocognitive TEAEs were observed. One death occurred due to COVID-19 (assessed as treatment-related by the investigator). Safety profile was manageable in the pt treated in an outpatient setting. Conclusions: At a longer median follow-up of 9.7 mo, a single cilta-cel infusion led to early and deep responses in pts with MM who had 1-3 prior LOT and were lenalidomide-refractory. ORR in this cohort was consistent with the CARTITUDE-1 study in heavily pretreated pts; responses deepened over time, with 92% of MRD-evaluable pts achieving MRD 10 -5 negativity. The safety profile was manageable; CRS was mostly gr 1/2, and no movement and neurocognitive TEAEs occurred, suggesting the efficacy of monitoring and pt management strategies that were implemented across phase 2/3 studies in the CARTITUDE program. Follow-up is ongoing, including additional enrollment in this cohort; this pt population is being further evaluated in the CARTITUDE-4 study (NCT04181827). Figure 1 Figure 1. Disclosures Cohen: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Research Funding; neopharm / promedico: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cohen: Janssen: Consultancy; Takeda: Consultancy; AstraZeneca: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; BMS/Celgene: Consultancy; Novartis: Research Funding; Oncopeptides: Consultancy; Genentech/Roche: Consultancy. Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Hillengass: Adaptive: Membership on an entity's Board of Directors or advisory committees; Beijing Medical Award Foundation: Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Beijing Life Oasis Public Service Center: Speakers Bureau; Curio Science: Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Axxess Network: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Skyline: Membership on an entity's Board of Directors or advisory committees. Goldschmidt: GSK: Honoraria; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding. Weisel: Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raab: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Roche: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. De Braganca: Janssen: Current Employment. Varsos: Janssen: Current Employment. Yeh: Janssen: Current Employment. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Corsale: Janssen: Current Employment. Akram: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech: Current Employment. Nesheiwat: Legend Biotech USA: Current Employment. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: At the time of abstract submission, cilta-cel is being investigated for the treatment of multiple myeloma but is not yet approved.

Introduction: Patients (pts) with multiple myeloma (MM) who experience early clinical relapse, defined as disease progression ≤12 mo after autologous stem cell transplantation (ASCT) or start of initial treatment (tx), have median overall survival rates Methods: Eligible pts had MM, received 1 prior line of therapy (PI and IMiD required), had disease progression per IMWG criteria (either ≤12 mo after ASCT or ≤12 mo after start of anti-myeloma therapy for pts who did not undergo ASCT), and were tx-naïve to CAR-T or anti-BCMA therapies. A single cilta-cel infusion (target dose 0.75×10 6 CAR+ viable T cells/kg) was given 5-7 d after start of lymphodepletion (300 mg/m 2 cyclophosphamide and 30 mg/m 2 fludarabine daily for 3 d). The primary objective was minimal residual disease (MRD) negativity at 10 -5, as assessed by next generation sequencing. Adverse events (AEs) were graded using CTCAE v5.0 (cytokine release syndrome [CRS]) and immune effector cell associated neurotoxicity syndrome (ICANS) by ASTCT criteria. To minimize risk of movement and neurocognitive tx-emergent AEs (TEAEs), pt management strategy was implemented, consisting of enhanced bridging therapy to reduce baseline tumor burden, early aggressive tx of CRS and ICANS, and handwriting assessment tools for early detection of neurotoxicity symptoms. Results: As of the April 15, 2021, data cutoff, 18 pts (median age 57.0 y [range 44-67]; 78% male) received cilta-cel, and 2 pts died before cilta-cel infusion (1 each due to progressive disease and worsening general status). Median follow-up was 4.7 mo (range 0.6-13.5); median time from diagnosis to enrollment was 1.1 y (range 0.5-1.9). Two (11.1%) pts had high cytogenetic risk and 5 (27.8%) had bone marrow plasma cells >30%; 14 (77.8%) pts received prior ASCT, and 15 (83.3%) were refractory to their prior therapy. Overall response rate was 88.9% (95% CI: 65.3-98.6), 27.8% of pts (95% CI: 9.7-53.5) achieved ≥complete response (CR), and 66.7% (95% CI: 41.0-86.7) achieved ≥very good partial response (VGPR). Median time to first response was 0.9 mo (range 0.9-2.6), median time to best response was 1.4 mo (range 0.9-11.8), and median time to ≥CR was 1.8 mo (range 0.9-11.6). Of the 13 pts with ≥3 mo follow up, 5 (38%) achieved ≥CR. Of pts who were MRD-evaluable (n=9), all were MRD 10 -5 negative (100% [95% CI: 66.4-100]). At data cutoff, all but 1 pt remained in clinical response (Figure). Hematologic TEAEs in ≥20% of pts were neutropenia (88.9%), thrombocytopenia (61.1%), anemia (50.0%), leukopenia (27.8%), and lymphopenia (22.2%). CRS occurred in 15 (83.3%) pts (1 gr 4); median time to onset was 8 d (range 5-11), consistent with the heavily pretreated pts in the CARTITUDE-1 study. Median duration of CRS was 4 d (range 1-7). ICANS (gr 1) occurred in 1 pt. One pt experienced movement and neurocognitive TEAEs (gr 3) on Day 38 post cilta-cel infusion. This pt had high disease burden at baseline, progressive disease despite triplet bridging therapy, and gr 4 CRS which have been identified as risk factors for movement and neurocognitive TEAEs. The pt was treated with immune-directed measures and was reported to be stable with some improvements at data cutoff and achieved VGPR. No study deaths occurred post cilta-cel infusion. Conclusions: A single cilta-cel infusion led to early and deep responses in pts who experienced early clinical relapse/tx failure to initial therapy, with a manageable safety profile. MRD negativity was achieved early. Responses continue to deepen, and follow-up is ongoing, including MRD assessment. These findings support the continued exploration of cilta-cel in earlier lines of treatment and incorporation into potentially curative front-line regimens. Figure 1 Figure 1. Disclosures Van de Donk: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cellectis: Research Funding; Takeda: Consultancy; Roche: Consultancy; Novartis /bayer/servier: Consultancy. Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Cohen: Takeda: Consultancy; Janssen: Consultancy; BMS/Celgene: Consultancy; Novartis: Research Funding; AstraZeneca: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech/Roche: Consultancy; Oncopeptides: Consultancy. Cohen: GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Research Funding; Neopharm / Promedico: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau. Hillengass: Curio Science: Speakers Bureau; Beijing Medical Award Foundation: Speakers Bureau; Beijing Life Oasis Public Service Center: Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Skyline: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Axxess Network: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Kerre: BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Elyad: Membership on an entity's Board of Directors or advisory committees. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. De Braganca: Janssen: Current Employment. Varsos: Janssen: Current Employment. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Zudaire: Janssen: Current Employment. Corsale: Janssen: Current Employment. Akram: Legend Biotech USA: Current Employment. Geng: Legend Biotech USA: Current Employment. Nesheiwat: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech: Current Employment. Sonneveld: Karyopharm: Consultancy, Honoraria, Research Funding; SkylineDx: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Zweegman: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: 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, Research Funding. OffLabel Disclosure: At the time of abstract submission, cilta-cel is being investigated for the treatment of multiple myeloma but is not yet approved.

Background Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy expressing two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating the safety and efficacy of cilta-cel in various clinical settings for patients (pts) with multiple myeloma (MM) and exploring suitability of outpatient administration. Initial results from Cohort A are presented here. Methods Pts from Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had not received BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). Minimal residual disease (MRD) negativity at 10-5 was the primary objective, and response rates (per IMWG) and safety (per CTCAE; CRS and ICANS by ASTCT) were secondary outcomes. Results At data cutoff (Feb 2021), the median follow-up was 5.8 months (2.5–9.8). Twenty pts (65% male; median age 60 years [38–75]) had received cilta-cel, with 1 pt treated in an outpatient setting. The median number of prior LOT was 2 (1–3): Conclusion Early and deep responses with manageable safety were demonstrated after a single cilta-cel infusion at the recommended phase 2 dose. Updated findings will inform suitability of outpatient treatment for this study and for the CARTITUDE-2 and CARTITUDE-4 studies.

8028 Background: Cilta-cel (JNJ-68284528) is a chimeric antigen receptor T (CAR-T)-cell therapy with 2 BCMA-targeting, single-domain antibodies designed to confer high avidity binding. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficacy and safety of cilta-cel in patients (pts) with MM in various clinical settings. Here, we describe the mitigation and management strategies implemented to identify and reduce the risk for neurologic adverse events (AEs) in Cohort A pts (progressive MM after 1−3 prior lines of therapy). Methods: Eligible pts (≥18 years of age) had MM per IMWG criteria, measurable disease, ECOG ≤1, progressive disease after 1−3 prior lines of therapy (including a PI and IMiD) and were lenalidomide refractory (no prior BCMA-targeting agent). Cilta-cel (0.75×106 [range 0.5–1.0×106] CAR+ viable T cells/kg) was given as a single infusion 5–7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). Monitoring and mitigation strategies for neurologic AEs include providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T-related ICANS using the ICE tool, regular handwriting assessments to detect micrographia, and neuroimaging (brain MRI) and EEG for pts with prior neurologic disease. Management strategies include evaluating infectious and paraneoplastic etiologies upon observation of ICANS ≥Grade (gr) 1, administration of tocilizumab (if concurrent CRS, all gr of ICANS) and/or dexamethasone (gr 2/3) or methylprednisolone (gr 4). ICANS and CRS were graded by ASTCT criteria; neurotoxicities not classified as ICANS were graded per CTCAE Version 5.0. Results: As of 15 Jan 2021 (median follow-up: 5.8 months [range: 2.5–9.8 months]), 20 pts in Cohort A received cilta-cel. Median age was 60 years (range: 38–75); 65% were male. Neurotoxicities occurred in 4 pts (20%). Three pts had ICANS (gr 1/2); median time to onset of symptoms was 8 days (range: 7–11) and median duration was 2 days (range: 1–2). Two of the 3 pts received supportive measures to treat ICANS, including levetiracetam and steroids; all 3 had concurrent CRS and all recovered. One pt developed isolated facial paralysis (gr 2) on Day 29 after cilta-cel infusion, and recovered 51 days after the onset of event following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported. Conclusions: Neurologic AEs were generally manageable in pts with MM following treatment with cilta-cel. With a median of 5.8 months of follow-up, there were no movement or neurocognitive disorders in pts from Cohort A. These results suggest that early detection and management of neurologic AEs can lead to better treatment outcomes. Clinical trial information: NCT04133636.

8013 Background: Cilta-cel is a CAR T-cell therapy expressing two BCMA-targeting, single-domain antibodies designed to confer avidity. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for patients (pts) with MM and exploring suitability of outpatient administration. Here, we present initial results from Cohort A. Methods: Cohort A pts had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was given 5–7 days (d) after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 d). The primary objective was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (IMWG) and safety (per CTCAE; CRS and ICANS by ASTCT). Results: As of Feb 2021 data cutoff (median follow-up: 5.8 months [mo]; range: 2.5–9.8 mos), 20 pts (65% male; median age 60 years [38–75]) received cilta-cel; 1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (1–3); 12 pts received < 3 prior lines and 8 received 3 prior LOT. All pts were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT; 40% were triple refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 mo (0.7–3.3); median time to best response was 1.9 mo (0.9–5.1). Median duration of response was not reached. All pts (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%; gr 3/4: 90%), thrombocytopenia (80%; gr 3/4: 35%), anemia (65%; gr 3/4: 40%), lymphopenia (60%; gr 3/4: 55%), and leukopenia (55%; all gr 3/4). CRS occurred in 85% of pts; 10% were gr 3/4. Median time to CRS onset was 7 d (5–9), with a median duration of 3.5 d (2–11). CAR T-cell neurotoxicity occurred in 20% of pts (all gr 1/2). Three pts had ICANS (1 gr 1; 2 gr 2); median time to onset was 8 d (7–11) and median duration was 2 d (1–2). One pt had gr 2 facial paralysis; time to onset was 29 d with a duration of 51 d. One death occurred due to COVID-19 (assessed as treatment (tx)-related by investigator). Safety profile was manageable in the pt treated in an outpatient setting. Conclusions: A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in pts with MM who had 1–3 prior LOT. Updated efficacy and safety findings will inform suitability of outpatient tx in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study. Clinical trial information: NCT04133636.

BACKGROUND: Patients with TD lower-risk (LR)-MDS relapsed or refractory to ESA have limited treatment options. Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomere lengths and active telomerase, characteristics observed in some MDS patients. IMerge is an ongoing global study of imetelstat in RBC TD patients with LR-MDS (IPSS Low or Int-1). In the first 32 patients enrolled, 8-week TI rate was 34%, with 24-week TI of 16%, and HI-E of 59%. The most frequently reported adverse events were reversible grade ≥3 cytopenias (Fenaux et al EHA 2018 Abstr S1157). Higher response rates were observed in patients (n=13) who were LEN and HMA naïve without del(5q). We report here results in an additional 25 LEN and HMA naïve patients without del(5q), with longer term follow-up of the 13 initial patients meeting the same criteria. METHODS: IMerge is a phase 2/3 trial (NCT02598661) that includes LR-MDS patients with a high transfusion burden (≥4 units / 8 weeks) who are relapsed/refractory to ESA or have sEPO >500 mU/mL. The additional 25 were required to be LEN and HMA naïve and lack del(5q). Imetelstat 7.5 mg/kg was administered IV every 4 weeks. In addition to the key endpoints noted above, secondary endpoints include safety, time to and duration of TI. Biomarkers are also being explored, including telomerase activity, hTERT, telomere length, and genetic mutations. RESULTS: Overall, for the 38 LEN/HMA naïve and non-del(5q) patients, median age was 71.5 years and 66% were men. 63% of patients were IPSS Low and 37% Int-1. Median prior RBC transfusion burden was 8.0 (range 4-14) U, and 71% had WHO 2008 RARS or RCMD-RS. 9/37 (24%) patients with evaluable sEPO levels had baseline level >500 mU/mL. As of July 2018, with a median follow-up of 25.8 months for the initial 13 patients, and 5.2 months for the 25 recently included patients, the 8-week RBC-TI rate was 37% (14/38). Durability of 24-week TI responses was demonstrated, with a median duration of 10 months and the longest ongoing response now >2 years. Among the patients achieving durable TI, all showed a Hb rise of ≥3.0 g/dL compared to baseline during the transfusion-free interval. Response rates were similar in RARS/RCMD-RS (33% [9/27]) and other patients (27% [3/11]), and those with baseline EPO levels >500 mU/mL (33% [3/9]) and ≤500 mU/mL (32% [9/28]). Reversible grade ≥3 neutropenia and thrombocytopenia were each reported in 58% of the patients. Liver function test (LFT) elevations were mostly grade 1/2. Reversible grade 3 LFTelevations were observed in 3 (8%) patients on study. An independent Hepatic Review Committee deemed the observed LFT elevations were not imetelstat-related hepatic toxicities. SUMMARY / CONCLUSIONS: In this cohort of 38 non-del(5q) LR-MDS patients with a high RBC transfusion burden who were ESA relapsed/refractory and naïve to LEN/HMA, single-agent imetelstat yielded a TI rate of 37%, with a median duration of 10 months and limited side effects. Durable responses were characterized by transfusion independence >24 weeks and accompanied by Hb rise. Updated data will be presented. Disclosures Steensma: Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy. Platzbecker:Celgene: Research Funding. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Raza:Kura Oncology: Research Funding; Onconova: Research Funding, Speakers Bureau; Celgene: Research Funding; Novartis: Speakers Bureau; Geoptix: Speakers Bureau; Janssen: Research Funding; Syros: Research Funding. Santini:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding. Germing:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding. Font:Celgene: Membership on an entity's Board of Directors or advisory committees. Samarina:Janssen: Research Funding. Díez-Campelo:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Bussolari:Janssen: Employment, Equity Ownership. Sherman:Janssen: Employment, Equity Ownership. Sun:Janssen: Employment, Equity Ownership. Varsos:Janssen: Employment, Equity Ownership. Rose:Janssen: Employment, Equity Ownership. Fenaux:Roche: Honoraria; Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Learning Objectives After completing this course, the reader will be able to: List the recommendations in current clinical practice guidelines on epoetin alfa dosing and administration regimens for patients with cancer and chemotherapy-related anemia. Discuss the benefits associated with epoetin alfa therapy in cancer patients with anemia receiving chemotherapy, in terms of increased hemoglobin levels, lower transfusion needs, and improved quality of life. Explain how higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance dosing with epoetin alfa in anemic cancer patients undergoing chemotherapy may be beneficial, both to the patient and to the health care provider. Access and take the CME test online and receive one hour of AMA PRA category 1 credit atCME.TheOncologist.com Purpose. Epoetin alfa administered s.c. three times weekly or once weekly increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves quality of life in anemic cancer patients receiving chemotherapy. This study assessed the feasibility of using higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance doses to increase and then maintain adequate Hb levels in this population. Materials and Methods. In this open-label, nonrandomized, pilot study, anemic (baseline Hb ≤11 g/dl) cancer patients undergoing chemotherapy received initial doses of epoetin alfa of 60,000 U s.c. once weekly to increase Hb levels by at least 2 g/dl, followed by 120,000 U s.c. every 3 weeks to maintain Hb levels. The maximum treatment duration was 24 weeks. Results. The mean baseline Hb level was 10.1 ± 0.8 g/dl (n = 20). Once-weekly dosing resulted in mean Hb level increases of 1.0 ± 1.1 g/dl by week 4 and 2.9 ± 1.9 g/dl by week 8; 86% and 79% of patients evaluable at week 8 and week 12, respectively, demonstrated increases of at least 2 g/dl (target Hb level of ≥12 g/dl). Thirteen patients (65%) received at least one maintenance dose; the mean Hb level increased from 12.8 ± 1.1 g/dl before starting maintenance therapy to 13.3 ± 1.4 g/dl at the last maintenance week. Both dosage regimens were well tolerated. Conclusions. Once-weekly epoetin alfa at a dose of 60,000 U effectively increased Hb levels by week 8; 86% of patients achieved rises of at least 2 g/dl or Hb levels ≥12 g/dl. Moreover, epoetin alfa at doses of 120,000 U every 3 weeks maintained or increased Hb levels. Results from this pilot study suggest that higher initial once-weekly dosing of epoetin alfa followed by less frequent maintenance dosing appears to be feasible for treating anemia in cancer patients undergoing chemotherapy. Further evaluation of these and other epoetin alfa dosage regimens is warranted.