The safety, kinetics and efficacy of plerixafor+pegfilgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization are poorly understood. We treated 12 study patients (SP; lymphoma n = 10 or myeloma n = 2) with pegfilgrastim (6 mg SC stat D1) and plerixafor (0.24 mg/kg SC nocte from D3). Six SP were 'predicted poor-mobilizers' and six were 'predicted adequate-mobilizers'. Peripheral blood (PB) CD34 + monitoring commenced on D3. Apheresis commenced on D4. Comparison was with 22 historical controls (HC; lymphoma n = 18, myeloma n = 4; poor mobilizers n = 4), mobilized with pegfilgrastim alone. Eight (67%) SP had PB CD34 + count ⩽ 5 × 10 6 /L D3 post pegfilgrastim; all SP surpassed this threshold the morning after plerixafor. In SP, PBCD34 + counts peaked D4 6/12 (50%), remaining ⩾ 5 × 10 6 /L for 4 days in 8/12 (67%). All SP successfully yielded target cell numbers (⩾2 × 10 6 /kg) within four aphereses. After maximum four aphereses, median total CD34+ yield was higher in SP than HC; 8.0 (range 2.4-12.9) vs 4.8 (0.4-14.0) × 10 6 /kg (P = 0.04). Seven of twelve (58%) SP achieved target yield after one apheresis. Flow cytometry revealed no tumor cells in PB or apheresis product of SP. Plerixafor+pegfilgrastim was well tolerated with bone pain (n = 2), diarrhoea (n = 2) and facial paraesthesiae (n = 3). Plerixafor+pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers, and is superior to pegfilgrastim alone.

2256 Plerixafor (Mozobil®) is indicated in combination with daily filgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization and subsequent autologous transplantation in patients with non-Hodgkin Lymphoma and multiple myeloma. In off-label use, pegfilgrastim (Neulasta®) is known to mobilize HSPC with a single injection. We hypothesise that pegfilgrastim is an attractive adjunct to plerixafor as a combination mobilizing regimen in both good- and poor-HSPC mobilizer patients, much like filgrastim but with the advantage to the patient of fewer injections. To-date there have been no published trials examining this combination. Aim: To investigate the tolerability, kinetics and efficacy of plerixafor plus pegfilgrastim for HSPC mobilization in patients with lymphoma or myeloma. Method: Twelve patients with lymphoma (n=10) and myeloma (n=2) underwent HSPC mobilization using single-dose pegfilgrastim (6mg SC mane D1) and nightly plerixafor (0.24 mg/kg SC nightly commencing 2200–2300hrs D3). Peripheral blood (PB) CD34+ monitoring commenced D3 and continued until the completion of apheresis. Apheresis commenced in all patients on D4. Nightly plerixafor/daily apheresis continued for up four doses/procedures, or until the target CD34+ yield (5×106/kg) was reached. CD34+ yields and kinetics were compared with historical controls mobilized with pegfilgrastim alone. Historical controls were mobilized with a single pegfilgrastim injection (6mg or 12mg SC mane D1), and PB CD34+ monitoring commenced on D4. Patients: Six ‘predicted poor-mobilizers’ (5 prior failed, 1 fludarabine-exposed) and 6 ‘predicted adequate-mobilizers’ were mobilized with pegfilgrastim plus plerixafor. Historical controls (n=22; 4 poor mobilizers) were mobilized with pegfilgrastim alone. Results: Four of 12(33%) study patients had a PB CD34+ count ≥5×106/L (our institutional threshold for collection) on D3 post-pegfilgrastim, however apheresis was commenced on D4 in all patients; all study patients surpassed this threshold by D4 (i.e. post-D3 evening dose of plerixafor). PB CD34+ counts peaked on D4 in 6/12 study patients and were sustained ≥5×106/L for 4 and 5 days in 8/12(67%) and 4/12(33%), respectively. Compared to historical controls, study patients were more heavily pre-treated (median prior regimens 2(1-4) vs. 1(0-2); P=0.002), and contained a higher proportion of poor mobilizers (50% vs. 18%; P=0.06). All study patients and 20/22 controls collected ≥2×106/kg CD34+ cells within 4 aphereses (P=0.53). Eleven of 12(92%) study patients vs. 16/22(76%) controls achieved this target after 2 apheresis procedures (P=0.37). After a maximum of 4 aphereses, there was a trend to higher median total CD34+ yields in the plerixafor plus pegfilgrastim patients compared to pegfilgrastim-alone patients; 8.0 ×106/kg (2.4-12.9 ×106/kg) vs. 4.8 (0.4-14.0 ×106/kg) (P=0.07), within a median of 1(1-4) vs. 2(1-4) collections (P=0.57). Study patients were assessed for the presence of tumor cells in the PB or apheresis product. One study patient with minimal BM involvement by lymphoplasmacytic lymphoma at baseline developed minimal detectable plasma cells in the PB and the apheresis product on D4 (post-plerixafor). One historical control patient with POEMS syndrome developed hyperleukocytosis after 12mg pegfilgrastim, which resolved without incident. The plerixafor plus pegfilgrastim combination was well tolerated: bone pain (worst grade=3, n=2), gastrointestinal symptoms (diarrhoea: worst grade=2, n=2) and facial paraesthesiae (n=3) were the most frequent adverse events. Engraftment data is currently being collected. Conclusion: Plerixafor plus pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers. Comparison with historical controls suggests that the addition of plerixafor to pegfilgrastim may overcome risk factors for failed mobilization such as prior mobilization failure and heavy prior chemotherapy exposure, enabling even predicted poor mobilizer patients to achieve target CD34+ yields, often within just two apheresis procedures. Disclosures: Herbert: Genzyme: Research Funding, Speakers Bureau; Amgen: Speakers Bureau. Off Label Use: Pegfilgrastim was used for hematopoietic stem and progenitor cell mobilization, which is an off-label indication. The use of pegfilgrastim for this purpose is widely published. Prince: Amgen: Consultancy, Honoraria, Research Funding.

Background Carfilzomib (K), a second generation proteasome inhibitor that is approved for patients (pts) with relapsed refractory multiple myeloma (RRMM) is associated with increased cardiovascular (CV) adverse effects (AE), in particular hypertension (HTN), dyspnea and cardiac failure (CCF), based on the ENDEAVOR (Dimopoulos, MA. et al. Lancet 2016) and ASPIRE studies (Stewart, K.et al. NEJM 2015). The clinical characteristic and underlying mechanism of K induced CVAE have been poorly elucidated, and the limited published data on the utility of cardiac enzymes as biomarkers have not been revealing. We conducted a retrospective single centre review of K-treated pts who have undergone systemic serial cardiovascular and cardiac enzyme assessment, to profile the nature of CVAE and patterns in cardiac enzymes that might have predictive utility in K-induced CVAE. Method: Between January 2016 to June 2018, all pts who were treated with K (D1,2,8,9,15,16 in a 28 day cycle)-based regimen for RRMM at St.Vincent's Hospital Melbourne underwent systematic cardiovascular assessment including documentation of baseline cardiac risk factors (RF) and transthoracic echo (TTE). Serial troponin, creatinine kinase (CK) and B-type Natriuretic Peptide (BNP) were performed at baseline (C1D1 or 2), mid cycle (D8 or 9) and end of treatment (D16) of every cycle. Repeat TTE was done at physicians' discretion. Systematic documentations of CVAEs (graded according to CTCAEv5) were retrieved from medical records. The incidence and severity of CVAE was collated and correlated with serial cardiac enzyme levels, the association of which was tested using Student's t-test. Results 76 pts (67% male; median age 66(46-86) years) with RRMM who received a median of 6 cycles (1-26) of K-based treatment were included in this analysis. At baseline, 16 pts (21%) had at least 1 CVRF including HTN, history of ischaemic heart disease, hyperlipidaemia, diabetes or smoking. The incidence of HTN prior to treatment was 39%. On treatment, the incidence of HTN was 85% (28% grade≥3). 17% of pts required the addition of antihypertensive medications and 11% had K dose reduction due to HTN. K-related dyspnea occurred in 53% of pts (28% grade≥3), 52% of who required K dose reduction/interruption. CCF occurred in 14.5% (grade≥3, 13%) that all necessitated K interruption/dose reduction. 69 pts had baseline TTE that showed a median RVSP (right ventricular systolic pressure) of 32mmHg (range 20-48). On treatment, 38 pts had repeat TTE, mainly driven by dyspnea with a median RVSP of 41(20-93mmHg). Of the 18 pts with grade≥3 dyspnea who had repeat TTE, 83% had RSVP ≥39mmHg and 33% had RVSP≥50mmHg, compared to 70% with RSVP ≥39mmHg and 10% RVSP≥50mmHg in the group with grade 1-2 dyspnea. Troponin_I and CK level did not change significantly throughout K-treatment. However BNP level rose and fell within each cycle, typically with peaks at mid cycle (D9 and D16) and troughs at the beginning of a new cycle (D1 or 2). 87.1% of pts had at least one elevated BNP (>100ng/L) with a median maximal level of 300ng/L (range 114-2320ng/L). There was a significant difference in the incidence of grade ≥3 CVAEs (mainly HTN) in pts whose mid cycle BNPs (D9 or 16) were elevated in ≥50% of measurements during the first 4 cycles of K compared to the rest (65.5% vs. 25.0%, p=0.0084). In pts with dyspnea, persistent rise in mid cycle BNPs that does not normalise prior to next treatment cycle trended towards an increased incidence of raised RVSP of ≥39mmHg (21.7% vs. 7.9%, p=0.0543). Conclusion. The incidence of CVAEs in pts treated with K is higher in the real-world setting compared to that reported in the Endeavor and ASPIRE studies. Dyspnea is frequent, the degree of which correlates with the degree of raised RVSP, thus indicating pulmonary hypertension as a contributor to dyspnea in the setting of K treatment. BNP level typically peaks during mid cycle and troughs at the beginning of next cycle, indicating a temporal relationship to K infusions. In pts with dyspnea, the association of persistent rise in mid-cycle BNP (rather than troponin or CK) with raised RVSP and HTN perhaps indicate transient endothelial dysfunction as the mechanism for K-induced CVAE rather than myocyte injury. Disclosures Quach: Amgen: Consultancy, Research Funding; Sanofi Genzyme: Research Funding; Janssen Cilag: Consultancy; Celgene: Consultancy, Research Funding. Tam:Roche: Honoraria; AbbVie: Honoraria, Research Funding; Pharmacyclics: Honoraria, Travel funding; Beigene: Honoraria, Other: Travel funding; Pharmacyclics: Honoraria; Gilead: Honoraria; Janssen: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Beigene: Honoraria, Other: Travel funding; Gilead: Honoraria; Roche: Honoraria.