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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.

This study used the latest available data cuts from the CARTITUDE-1 and KarMMa clinical trials to update previously published matching-adjusted indirect treatment comparisons (MAICs) assessing the comparative efficacy of ciltacabtagene autoleucel (cilta-cel) versus the FDA-approved idecabtagene vicleucel (ide-cel) dose range of 300 to 450 × 106 CAR-positive T-cells in the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were previously treated with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody (i.e. triple-class exposed). MAICs were performed with the latest available individual patient data for cilta-cel (CARTITUDE-1) and published summary-level data for ide-cel (KarMMa). The analyses included treated patients from CARTITUDE-1 who satisfied the eligibility criteria for KarMMa. The MAIC adjusted for unbalanced baseline covariates of prognostic significance identified in the literature and by clinical expertise. Comparative efficacy was assessed for overall response rate (ORR), complete response or better (≥CR) rate, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Cilta-cel was associated with statistically significantly improved ORR (odds ratio [OR]: 94.93 [95% confidence interval [CI]: 21.86, 412.25; p < .0001]; relative risk [RR]: 1.34), ≥CR rate (OR: 5.65 [95% CI: 2.51, 12.69; p < .0001]; RR: 2.23), DoR (hazard ratio [HR]: 0.52 [95% CI: 0.30, 0.88; p = .0152]), PFS, (HR: 0.38 [95% CI: 0.24, 0.62; p < .0001]), and OS (HR: 0.43 [95% CI: 0.22, 0.88; p = .0200]) compared with ide-cel. These analyses demonstrate improved efficacy with cilta-cel versus ide-cel for all outcomes over longer follow-up and highlight its therapeutic potential in triple-class exposed RRMM patients.

[Objective]: In the absence of head-to-head trials, indirect treatment comparisons (ITCs) between ciltacabtagene autoleucel (cilta-cel; in CARTITUDE-1) and treatments used in real-world clinical practice (physician’s choice of treatment [PCT]), were previously conducted. We conducted multiple meta-analyses using available ITC data to consolidate the effectiveness of cilta-cel versus PCT for patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM). [Methods]: Five ITCs were assessed for similarity to ensure robust comparisons using meta-analysis. Effectiveness outcomes were overall survival (OS), progression-free survival (PFS), time to next treatment (TTNT), and overall response rate (ORR). A robust variance estimator was used to account for the use of CARTITUDE-1 in each pairwise ITC. Analyses were conducted in both treated and enrolled populations of CARTITUDE-1. [Results]: Four ITCs were combined for evaluation of OS. Results were statistically significantly in favor of cilta-cel versus PCT in treated patients (hazard ratio [HR]: 0.24, 95% confidence interval [CI]: 0.22–0.26). Three ITCs were combined for evaluation of PFS and TTNT. Cilta-cel reduced the risk of progression and receiving a subsequent treatment by 80% (HR: 0.20 [95% CI: 0.06, 0.70]) and 83% (HR: 0.17 [95% CI: 0.12, 0.26]), respectively. Three ITCs were combined for evaluation of ORR. Cilta-cel increased the odds of achieving an overall response by 86-times versus PCT in treated patients. Findings were consistent in the enrolled populations and across sensitivity analyses. [Conclusions]: Evaluating multiple indirect comparisons, cilta-cel demonstrated a significantly superior advantage over PCT, highlighting its effectiveness as a therapy in patients with triple-class exposed RRMM., The CARTITUDE-1 study and these analyses were funded by Janssen Research & Development, LLC, and Legend Biotech, Inc. Medical writing support was provided by EVERSANA and funded by Janssen Global Services, LLC.

Janssen ResearchDevelopment, LLC, part of the Janssen pharmaceutical companies of JohnsonJohnson, and NYU School of Medicine partnered to establish the Compassionate Use Advisory Committee (CompAC) to evaluate the use of an independent, external, expert committee in ensuring transparent, fair, beneficent, evidence-based, and patient-focused compassionate access to investigational medicines, a public health challenge that has been an ongoing issue for over 3 decades.To this end, NYU School of Medicine was responsible for the formation, member selection, and operation of CompAC, consisting of physicians, ethicists, and patient advocates, under JohnsonJohnson's sponsorship.A pilot was successfully run using CompAC to provide recommendations on compassionate use access to a JohnsonJohnson oncology investigational asset called daratumumab.This innovative model provides a framework that can be emulated by the industry globally.

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.

8030 Background: Evaluation of patient (pt)-reported outcomes provides insight into how real-life SOC treatments (tx) affect HRQoL for pts with RRMM. LocoMMotion (NCT04035226) is the first prospective, multinational study of real-life SOC in triple-class exposed pts with RRMM. Here, we present measures of symptoms, functioning, and overall HRQoL. Methods: LocoMMotion is a prospective, noninterventional study across 76 sites (63 European; 13 US). Pts had received ≥3 prior lines of therapy (LOT) or were refractory to PI and IMiD; received PI, IMiD, and anti-CD38 mAb; and had disease progression during/after last LOT. Real-life SOC tx were defined as those used in local clinical practice. The questionnaires were EORTC QLQ-C30, 4 single items from EORTC QLQ-MY20, and EQ 5D-5L. HRQoL was assessed at baseline (BL), day 1 of each tx cycle, end of tx visit, and during the follow-up period (every 4 weeks). Improvement compared to BL health status was evaluated using established thresholds. Within-group change was assessed using mixed models for repeated measures. Results: Questionnaire completion for pts in the LocoMMotion study (N=248; 54.4% male; median age 68 yrs; median 4.0 [range, 1–20] cycles of SOC) was 75.6% during SOC tx. Most pts did not achieve meaningful improvement in PRO scores, defined by a literature-based minimally important difference of 10 points in mean score. This was most pronounced in pain symptoms (62% of pts had no meaningful improvement during the first 3 months of tx; 55% had no improvement during full tx duration). For the overall population, the least square (LS) mean changes from BL during SOC tx and subsequent LOT are described (Table). Pts who achieved very good partial response and better during SOC tx had greater improvement in PRO scores, including in LS mean change for pain score (-14.9 [95% confidence interval (CI): -22.9, -7.0]). Conclusions: In this first prospective study of real-life current SOC in triple-class exposed pts, limited gains in HRQoL were reported, most notably in pain symptoms. There is an urgent need for effective therapies that can help pts achieve deep responses and delay disease progression, as these are associated with improved HRQoL. Clinical trial information: NCT04035226. [Table: see text]

8031 Background: Patients (pts) with RRMM who are triple-class exposed (proteasome inhibitor [PI], immunomodulatory drug [IMiD], and anti-CD38 monoclonal antibody [mAb]) have an urgent and currently unmet clinical need. LocoMMotion (NCT04035226) is the first prospective multinational study of real-life SOC in triple-class exposed pts with RRMM. Here we present efficacy in subgroups of pts treated with SOC therapies in the LocoMMotion study. Methods: LocoMMotion is a noninterventional study across 76 sites (63 European; 13 US). Eligible pts had received ≥3 prior lines of therapy (LOT) or were double refractory to a PI and an IMiD; received a PI, an IMiD, and anti-CD38 mAb; and had disease progression during/after their last LOT. Real-life SOC treatments were defined as those used in local clinical practice. Responses and disease progression were assessed by response review committee, per IMWG criteria. Subgroups were defined by baseline (BL) characteristics: age, Eastern Cooperative Oncology Group performance status (ECOG PS), renal function, ISS stage, presence of extramedullary plasmacytoma, LDH level, % of bone marrow plasma cells, number of prior LOT, triple-class or penta-drug exposure, and refractoriness. Results: As of May 21, 2021 (median follow-up 11.0 mo), 248 pts were enrolled and treated with median 4.0 (range, 1–20) cycles of SOC therapy. Evaluation of efficacy outcomes in subgroups demonstrated that refractoriness to 3 classes of antimyeloma therapy, presence of extramedullary plasmacytomas, high LDH, and ECOG PS ≥1 were associated with generally worse outcomes, compared with pts who did not have these characteristics (Table). Overall response rate (ORR) ranged from 20.0–43.1% across all subgroups. Age and number of prior LOT did not have an impact on efficacy outcomes. Conclusions: Subgroup analyses of this first prospective study of real-life SOC tx in triple-class exposed pts with RRMM indicate that specific pt and disease characteristics were associated with poor outcomes. Triple-class refractory and non-triple-class refractory pts had poor outcomes, although the latter had longer median progression-free survival (PFS). These findings should be considered when planning bridging strategy for CAR-T therapy. Clinical trial information: NCT04035226. [Table: see text]

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.

450 Background: FGFR3 mutations appear to be enriched in luminal 1 UC, which have low expression of markers associated with an immune response, including CD8-T-effector gene expression levels. Objective response rate (ORR) to PD-1 and PD-L1 inhibitors in luminal 1 tumors appear lower (10-19%) than in infiltrated luminal 2 and basal 3 tumors (ORR 31-34%). This suggests FGFR3 mutations occur within a group of tumors less likely to benefit from immune checkpoint inhibition (ICI). Here we describe outcomes of a subgroup of pts with FGFR2/3 mutations and gene fusions, previously treated with PD-1/PD-L1 inhibitors and included in an ongoing erdafitinib phase 2 study. Methods: Patients who had received prior immunotherapy for advanced UC were selected from those enrolled on BLC2001, an ongoing phase 2, open-label study of the pan-FGFR inhibitor erdafitinib in subjects with advanced UC with specific FGFR2/3 gene alterations (NCT02365597). We explored investigator-reported clinical outcomes including ORR and median time to progression (TTP) of pts treated with ICI preceding erdafitinib therapy. Results: 28/203 pts had previously received anti PD-1 or anti PD-L1 treatment. In this subgroup, the median age was 67.0 y; 82% were male, 79% had an ECOG score ≤1, 36% had liver metastases, and 93% had ≥2 prior lines of systemic therapy. The response rate to anti PD-1/PD-L1 agents was 3.6% (95% CI, 0.1%-18.3%) with one partial response. Median TTP was 3.4 mo (range 2-15 mo; 95% CI, 2.3-4.9). Conclusions: In this post-hoc analysis, FGFR mutations and gene fusions seem to select for a group of pts less likely to respond to immune checkpoint inhibition. Although caution is needed due to the retrospective nature of the data, the presence of these alterations may reflect an unmet need with currently approved agents. This finding highlights the need for FGFR alteration testing and an effective FGFR-targeted therapy. Clinical trial information: NCT02365597.

beta-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with beta-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced beta-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease. beta-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with beta-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced beta-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease. Abstract beta-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with beta-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced beta-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease.

Allogeneic BMT represents the only chance of cure for beta-thalassemia. Occasionally, two affected individuals from the same family share a matched healthy sibling. Moreover, a high incidence of transplant rejection is still observed in Pesaro class III patients, requiring a second BMT procedure. In these settings, one option is to perform a second BM harvest from the same donor. Although BM harvest is a safe procedure in children, ethical issues concerning this invasive practice still arise. Here, we describe our series of seven pediatric, healthy donors, who donated BM more than once in favor of their beta-thalassemic HLA-identical siblings between June 2005 and January 2008. Three donors donated BM twice to two affected siblings and four donors donated twice for the same sibling following graft rejection of the first BMT. All donors tolerated the procedures well and no relevant side effects occurred. There was no significant difference between the two harvests concerning cell yield and time to engraftment. Our experience shows that for pediatric donors, a second BM donation is safe and feasible and good cellularity can be obtained. We suggest that a second harvest of a pediatric donor can be performed when a strong indication for BMT exists. Allogeneic BMT represents the only chance of cure for beta-thalassemia. Occasionally, two affected individuals from the same family share a matched healthy sibling. Moreover, a high incidence of transplant rejection is still observed in Pesaro class III patients, requiring a second BMT procedure. In these settings, one option is to perform a second BM harvest from the same donor. Although BM harvest is a safe procedure in children, ethical issues concerning this invasive practice still arise. Here, we describe our series of seven pediatric, healthy donors, who donated BM more than once in favor of their beta-thalassemic HLA-identical siblings between June 2005 and January 2008. Three donors donated BM twice to two affected siblings and four donors donated twice for the same sibling following graft rejection of the first BMT. All donors tolerated the procedures well and no relevant side effects occurred. There was no significant difference between the two harvests concerning cell yield and time to engraftment. Our experience shows that for pediatric donors, a second BM donation is safe and feasible and good cellularity can be obtained. We suggest that a second harvest of a pediatric donor can be performed when a strong indication for BMT exists.

In the developed world, the survival and quality of life of patients with beta thalassemia (Bthal) has dramatically improved with optimization of blood transfusions and iron chelation. By contrast, in countries with limited resources most affected children die before the age of 20 because of the unavailability of safe blood products, expensive iron chelating drugs and inadequate management of co-morbidities. For these patients allogeneic stem cell transplantation (SCT) from matched donors offers a cure with low morbidity and mortality. Between June 2005 and May 2008, 47 consecutive Bthal patients underwent SCT from an HLA identical sibling in our center, among these, 3 patients underwent 2 SCTs. Median age was 8 years (2–15), country of origin: Lebanon (9), Iraq (19), Palestine (3), Syria (16). One pt was classified as Lucarelli class I, 24 as class II and 22 as class III. Most patients had severe iron overload evidenced by irregular iron chelation (83%), median ferritin 2973 (956–14280), median liver iron concentration 22 mg Fe/g (6.9–95.7). Most patients had liver toxicity due to iron overload and hepatitis evidenced by median ALT 71 (12–545), AST 59 (18–371), liver fibrosis Ishak 3 (0–5), HepC pos 16/47 (34%). Patients had inadequate transfusional management evidence by a median pre-transfusion Hb of 8 g/dL and anti HLA antibodies in 81% pts. Class I-II patients were conditioned with a regimen based on iv busulphan (iv Bu, Busilvex®, dosage according to weight, adjusted from the 5th dose to a target AUC 1200 umol/min) and cyclophosphamide (Cy) 200mg/kg (n19) with the addition of thiotepa (TT 10mg/kg) if

Dear Editor In their publication of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal of eltrombopag, Boyers et al. [1] report the results of the indirect treatment comparison (ITC) of eltrombopag and romiplostim, conducted by GlaxoSmithKline (GSK) [the manufacturer of eltrombopag] and made available to NICE as part of the single technology appraisal of eltrombopag. Subsequent to the appraisal process, GSK identified and corrected a methodological error in this analysis (available at http://www.gsk-clinicalstudyregister.com [study ID: 114014]). NICE were made aware of this error in November 2010. This correction was not published as part of the original assessment of eltrombopag and is not used in the Boyers et al. publication [1]. GSK would like to alert the readers of PharmacoEconomics to the corrected data and interpretation of this analysis. The nature of the error, the corrected results and the impact on the conclusions of the article are outlined below.