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In Focus

58th American Society of Hematology Annual Meeting


Gene therapy for haemophilia B complete response, 51 had a complete central venous catheter-associated
Lindsey George (The University of response with incomplete blood thrombosis. Julie Jaray (University of
Pennsylvania, Philadelphia, PA, USA) count recovery, and 19 had a partial Southern California, Los Angeles, CA,
presented results from a clinical response (overall response, 88 [52%]). USA) presented the interim results of
trial where seven patients with Median overall survival in these a prospective, observational cohort
haemophilia B were treated with patients was 31 weeks (range 261). study including 1096 patients who
SPK-9001, a gene therapy treatment For all enrolled patients, progressive had 1233 central venous catheters
using a bioengineered AAV capsid disease (n=75), lack of ecacy (n=44), inserted. Peripherally inserted

Lan-Lan Smith
with liver specic tropism containing adverse events (n=34), and death central catheters (PICC) were placed
a transgene encoding FIX Padua, (n=29) were the most common in 827 (67%) cases and there were
a naturally occurring variant with reasons for treatment discontinuation. 406 (33%) centrally inserted tunnelled The 58th American Society of
much greater specific activity than Seven deaths were considered lines. The cumulative incidence of Hematology Annual Meeting
was held in San Diego, CA, USA
wild-type FIX. All patients received possibly related to treatment, from venous thromboembolism (VTE) on Dec 36, 2016.
a dose of 5 10 vg/kg, and steady- pul monary embolism, respiratory for the whole population was
state FIX expression was reached by failure, haemoptysis, intracranial 57% (75% PICC, 2% in tunneled
12 weeks after vector infusion. All bleeding, ventricular brillation, septic lines). In a multivariate analysis of
patients saw an increase in FIX activity, shock, and neutropaenia. The most 883 placements, risk of VTE was
with a mean increase of 323%. No commonly reported treatment-related associated with type of central venous
patients developed an inhibitor adverse events of any grade were catheter (tunnelled lines vs PICC, odds
against FIX, and only one patient diarrhoea (16%) and fatigue (15%). ratio 34 [95% CI 1482]), number
required FIX concentrate infusion for of lumens (single vs multiple 27
a bleed 2 days after vector infusion. Ibrutinib for cGVHD [1553]), history of VTE (no vs yes 28
Four of the patients who required David Miklos (Stanford University, [1265]), and gender (female vs male
regular prophylaxis before treatment Stanford, CA, USA) presented 05 [0309]).
were able to safely stop following the results of a phase 2 study
treatment. of ibrutinib in for patients with Mycosis fungoides and Szary
chronic graft versus host disease syndrome
Targeting of FLT3 mutations in (cGVHD) who were unsuccessfully Malignant T-cells in patients with
AML treated with corticosteroids. mycosis fungoides and Szary syn-
Gilteritinib is an oral FLT3 and AXL 42 patients were treated with drome can express PD-1 and PD-L1/
inhibitor with preclinical activity ibrutinib, and had a median of two PD-L2. Michael Khodadoust (Stanford
against both FLT3-ITD activating (range one to three) prior treatments. University School of Medicine,
muta tions and FLT3-Asp835 After a median follow-up of Stanford, CA, USA) presented
resistance mutations. Alexander Perl 139 months, 28 (67%) of 42 patients the results of a phase 2 study of
(University of Pennsylvania-Abramson had a cGVHD response based on pembrolizumab, which included
Comprehensive Cancer Center, the 2005 NIH consensus response 24 relapsed or refractory patients
Philadelphia, PA, USA) presented criteria (nine complete response, who received at least one dose of
the results of an open-label dose- 19 partial response). 20 (71%) of the the drug. Most were heavily treated
escalation study (NCT02014558) 28 patients had a response lasting with a median of four prior systemic
of gilteritinib in adult patients with 20 weeks or longer, and 12 (48%) of therapies (range 111). Nine patients
relapsed or refractory acute myeloid 25 patients with available data had a (38%) had an objective response with
leukaemia (AML). 252 patients were response lasting 32 weeks or longer. one complete response and eight
enrolled in the study with 177 (70%) Serious adverse events occurred in partial responses, and an additional
of patients having two or more lines 22 patients (52%), and the most nine patients had stable disease. In
of prior therapy. Although having a common adverse events (AEs) of all particular, improvements in skin
FLT3 mutation was not an inclusion grades were fatigue (57%), diarrhoea disease were observed in six patients.
criterion of the study, 194 patients (36%), muscle spasms (29%), nausea An adverse event which had not
had a locally conrmed FLT3 mutation. (26%), and bruising (24%). been observed in previous trials
When restricting the analysis to with pembrolizumub was immune-
patients who received 80 mg or more Catheter related thrombosis mediated skin flare reaction, seen
gilteritinib, and had a conrmed FLT3 There is limited evidence regarding exclusively in patients with Szary
mutation (n=169), 18 patients had a risk factors for paediatric patients and syndrome. Two patients had a

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In Focus

grade 2 reaction and four patients had treated with rivaroxaban. Among the liposomal formulation of cytarabine
grade 3. 70 patients included, 54 (77%) had and daunorubicin encapsulated at
a PICC with 16 (23%) having a port- a 5:1 molar ratio. Patients enrolled
Subcutaneous daratumumab a-cath line. The primary objective were aged 6075 years with newly
for myeloma was an estimate of the proportion diagnosed secondary AML or AML
Saad Usmani (Levine Cancer Institute/ of catheter survival at 3 months, with MDS-related cytogenetic
Carolinas HealthCare System, dened as infusion failure that does abnormalities. 153 patients were
Charlotte, NC, USA) presented the not respond to tissue plasminogen randomised to receive CPX-351, and
results of a phase 1b study on patients activator. Catheter survival was 586% 156 to receive a standard 7+3 regimen.
with relapsed or refractory multiple (95% CI 469694) at 12 weeks and 91 patients of the 125 eligible patients
myeloma, examining whether no catheters were removed due to received a transplantation, 52 (34%)
the combination of subcutaneous thrombosis. The 3-month incidence of of those treated with CPX-351 and
daratumumab along with admini- recurrent VTE was 143% (025766), 39 (25%) of those treated with 7+3.
stration of recombinant human one of which was a fatal pulmonary Overall survival, landmarked for time
hyaluronidase enzyme (rHuPH20) embolism. There were 11 bleeding of stem-cell transplantation showed
could facilitate systemic absorption events in nine patients. that patients treated with CPX-351
of daratumumab (NCT02519452). had significantly improved survival
Focusing on the patients in the Recombinant ADAMTS13 compared with those treated with
dose-escalation part of the study, Replacement of defective ADAMTS13 7+3 (HR 046, p=00046). Median
41 patients were treated with the in patients with hereditary thrombotic overall survival was not reached in
combination at 1200 mg (n=8) or thrombocytopenic purpura (TTP) with the CPX-351 group, and a median of
1800 mg (n=33) dose levels. Nine a recombinant version of the protein 1025 months (95% CI 6211669)
(22%) of the 41 patients reported may provide an alternative treatment was noted for those in the 7+3 group.
infusion-related reactions, which were option to plasma transfusions. Marie
mostly grade 1 or 2 in severity, which Scully (University College London Stopping TKIs in CML
including, fever, rigors, vomiting, Hospitals NHS Trust, London, UK) Francois-Xavier Mahon (University
itching, oedema of the tongue, non- presented data from a dose-escalation of Bordeaux, Bordeaux, France)
cardiac chest pain and wheezing. All study of a recombinant ADAMTS13 presented results from the European
of these AEs developed during the (BAX930), which was manufactured stop TKI (EURO-SKI) trial, which
first infusion and were controllable. using a plasma-free method. included 755 patients in chronic-
AEs observed in the study were 15 patients were treated on the study phase CML who had achieved a
similar to those seen with intravenous (three received 5 U/kg, three received deep molecular response (BCR-ABL
daratumumab. Five patients reported 20 U/kg, and nine received 40 U/kg). <001%, MR4) for at least a year, who
grade 3 or higher drug-related AEs, There were no binding or inhibitory had assessable molecular data for
including fatigue (n=2), influenza, anti-ADAMTS13 antibodies related to estimating molecular recurrence-free
hypertension, dyspnoea, and tumour rADAMTS13 infusion detected, and survival (MRFS). MRFS was 61% (95%
lysis syndrome. The second part of the no serious adverse events. There was CI 5865) at 6 months, 55% (5158)
trial will randomise patients to receive evidence of cleaved von Willebrand at 12 months, and 50% (4754) at
either subcutaneous daratumumab factor, and based on data from seven 24 months, indicating that stopping
with rHuPH20 versus intravenous patients treated with 40 U/kg, a TKIs can be feasible and safe. Mhairi
daratumumab. comparable pharmacokinetic profile Copland (University of Glasgow,
to that from plasma infusion studies. Glasgow, UK) presented results from
Managing upper extremity the British De-Escalation and Stopping
DVT in patients with cancer Liposome delivery for AML Therapy with Imatinib, Nilotinib or
Upper extremity deep vein thrombosis drugs sprYcel (DESTINY) study, which looked
(UEDVT) is often associated with Changing the delivery method can at de-escalating treatment, including
central venous catheter placement in be a way of improving tolerability of 49 patients who had only achieved
patients receiving chemotherapy for chemotherapy drugs. Jeffrey Lancet MR3 (BCR-ABL <01%). They found
cancer. Gwynivere Davies (University (H Lee Moffitt Cancer Center & that decreasing TKI treatment to half
of Calgary, Calgary, AB, Canada) Research Institute, Tampa, FL, USA) the standard dose appeared to be safe,
presented results of a multicentre presented results from an exploratory and was associated with improvement
prospective cohort study of adult analysis of patients who received an in TKI-related side eects.
patients with active malignancy allogeneic stem cell transplantation
and symptomatic proximal UEDVT, in a phase 3 trial of CPX-351, a Lan-Lan Smith

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