therapy in relapsedrefractory myeloma A UK multicentre experience Neil Rabin Consultant Haematologist o n behalf of Dr Nicola Maciocia University College London Hospitals UK 4 th November 2015 ID: 499731
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Pomalidomide therapy in relapsed/refractory myeloma: A UK multi-centre experience
Neil RabinConsultant Haematologiston behalf of Dr Nicola MaciociaUniversity College London Hospitals, UK4th November 2015
Maciocia
N,
Sharpley
F,
Belsham
E,
Schey
S, Benjamin R,
Streetly
M,
Jenner M,
Ramasamy
K, Yong KL, Rabin N. IMW 2015Slide2
Poor outcome for patients with Relapsed Refractory Myeloma
Kumar et al, Leukemia
2011Slide3
BackgroundPomalidomide + Dexamethasone licensed in Europe August 2013 for patients with relapsed/refractory myeloma, who have received at least two prior therapies (lenalidomide/bortezomib
) and have progressed on their last therapy.San Miguel J,
et al. Lancet Oncol.
2013
.Slide4
Pomalidomide treatment for patients with RRMMSan Miguel et al, Lancet Oncology 2013
Medain
PFS 4.0
vs
1.9
mo
Medain
PFS 12.7
vs
8.1
moSlide5
BackgroundPomalidomide available in England from December 2013 via National Cancer Drugs Fund:Adequate treatment with bortezomib
, lenalidomide, alkylatorRefractory to last line of therapyFailed treatment with bortezomib OR lenalidomide (different to MM-003 trial)Performance Status 0-2
No resistance to high dose dexamethasone
No peripheral neuropathy of grade 2 or moreSlide6
AimTo assess the real-world clinical efficacy of POMA-DEX within its licensed indication in a retrospective analysis of patients treated at 5 UK centresSlide7
University College London Hospitals NHS Foundation
TrustGuy’s and St.Thomas’ NHS Foundation TrustKing’s College London Foundation NHS Trust
Oxford University Hospitals NHS Foundation
Trust
University Hospital Southampton NHS Foundation TrustSlide8
MethodsAll patients who received Pomalidomide + Dexamethasone (until Feb 2015, data updated for this meeting)
Data collected retrospectively using a pre-defined proforma Prior myeloma therapy, and whether refractory to last RxRelapsed or refractory to Lenalidomide or BortezomibMeasurable disease (serum/urine paraprotein
, SFLC analysis)
Renal function
Cytogenetic (FISH) data
International Staging System
Response to
Pomalidomide
Toxicities – non haematological / haematological to
PomalidomideSlide9
MethodsTo be included in response analyses patients had to have IMWG measurable disease, and have received at least one cycle of Pomalidomide and DexamethasoneResponse assessed using IMWG criteria
High risk disease defined as per IMWG (ISS II/III and t(4;14) or 17p13del).Slide10
Results79 patients identified from August 2013 onwards. Followed until Feb 2015 (IMW abstract, updated for this meeting)62 (78.5%) suitable to be included
in response analyses.All patients received Pomalidomide (2-4mg D1-21) plus Dexamethasone. 30/79 (38%) received another agent(s): clarithromycin (23); cyclophosphamide (9
);
carfilzomib
(
1);
bortezomib
(
1
).
In 15 (50%) the third agent was added from start of therapy.
In 15 (50%) it was added midway through treatment.Slide11
Characteristic
Number (%) n = 79
Median age (years)
67 (40-89)
Sex
Male
45(57)
Female
34(43)
Isotype
IgG
43(54.4)
IgA
19(24)
Light chain only
14(17.7)
Non-secretory
1(1.3)
Bence Jones
1(1.3)
IgD
1(1.3)
Time from diagnosis (yrs)
4.86 (0.52-18.03)
CrCl < 45ml/min
14
/71 (20)
IMWG high risk
11/40 (27.5
)
No. of prior lines therapy
4 (1-8)Slide12
Previous treatments
Thalidomide
66 (83.5)
Lenalidomide
79 (100)
Bortezomib
78 (98.7)
ASCT
48 (60.8)
Refractory to bortezomib
19/76 (25)
Relapsed and refractory to
bortezomib
39/76 (51.3)
Intolerant of bortezomib
7/78 (8.9)
Refractory to
lenalidomide
/thalidomide
76 (96.2)
Double refractory
58 (73.4)
Refractory to last therapy
73 (92.4)Slide13
ResultsMedian FU was 13.7 months (0.9-42.8). Median
no of cycles was 4 (range 1-32).Median dose Pomalidomide 4 mg (range 2-4). In those with starting GFR <45ml/min, 50% (7/14) received < 4mg Pomalidomide. Slide14
Response RatesORR (≥ PR) was 53%, VGPR 5%, and >/= SD 94%.
UK
retrospective data
MM-003
Number (%) n = 62
No (%) n=302
Overall response rate
33(53)
95 (31)
Complete response
or
stringent
C
omplete
response
0 (0)
3 (1)
Very good partial response
3 (
4.7)
14 (5)
Partial response
30 (48.4)
78 (26)
Stable disease
25 (40)
129 (43)
Progressive disease
4(6.25)
29 (10)Slide15
SurvivalSlide16
ResultsPFS 4.8 mo, OS 16.3 mo. Median duration of response (DoR) 3.9 mo.
25/79 (32%) patients received further therapyMedian time to next treatment (TNT) 6.2 mo (0.3 – 18.5 mo.). Slide17
PFS
OS
RENAL
FUNCTION
CYTOGENETIC
RISK
DOUBLE VS
TRIPLE THERAPYSlide18
ToxicitiesGrade 3/4 non-haem toxicities occurred in 27/79 (34%) patients:
Non haem toxicities
(grade 3
/4)
No of episodes
(
%) n = 79
Lower
respiratory tract infection
15 (
19)
Neutropenic
sepsis
9 (11.4)
Acute
kidney injury
3 (
3.8)
Epistaxis
1
( 1.3
)
CVA
1 (
1.3)
Fatigue
1 (
1.3)
Hyperglycaemia
1 (
1.3)
ALT rise
1 (
1.3)
Nausea
1 (1.3
)
Constipation
1 (
1.3)
Venous
thrombosis
1 (
1.3)
Strangulated hernia
1 (
1.3)
Chronic sinusitis
1 (
1.3)Slide19
ToxicitiesGrade 3/4 haematological toxicitiesNeutropenia 28 patients (35%)Thrombocytopenia
in 17 patients (22%)Anaemia in 8 patients (10%).54 patients came off treatment during study period. 11/54 (20%) stopped due to toxicities41/54 (76%) stopped due to
PD
One patient developed lung ca, one death of unknown causeSlide20
ConclusionPOMA-DEX is effective in relapsed/refractory myeloma, with outcomes comparable to results from the phase 3 NIMBUS study (MM-003).Improved OS compared to published data (16.3 mo
vs 12.7 mo), equivalent PFS (4.8 mo vs 4.0 mo) Reduced renal function and adverse genetics do not appear to influence outcomes. The addition of a third agent should be explored prospectively in ongoing clinical trials.
Our rates of infection slightly higher than published data but toxicity still acceptable in this heavily pre-treated population.Slide21
AcknowledgementsUniversity College London Hospitals NHS Foundation TrustNicola
Maciocia, Andrew Melville, Simon Cheesman, Rakesh Popat, Shirley D’Sa, Ali Rismani,
Kwee
Yong, Neil Rabin
Guy’s and
St.Thomas
’ NHS Foundation
Trust
Matthew
Streetly
King’s College London Foundation NHS
Trust
Reuben Benjamin, Steve
Schey, Hanna RenshawOxford University Hospitals NHS Foundation Trust
Karthik
Ramasamy
, Faye
Sharpley
University
Hospital Southampton NHS Foundation
Trust
Matthew Jenner, Edward
Belshom
UK Myeloma Forum