1. Clinical cases and experiences of using Daratumumab therapy in the DGH setting
Dr Rachel Hall
Consultant Haematologist
Royal Bournemouth and Christchurch
NHS Foundation Trust

2. Clinical use of anti-CD38 MAb in Myeloma
Setting: open labelled Daratumumab single agent in
Relapsed after 3 prior therapies (IMID and PI x 2 cycles)
Double refractory (PD within 60 days of last IMID/PI)
Weekly Dara infusions cycles 1 and 2 (8 doses)
Fortnightly Dara infusions cycles 3-6 (8 doses)
Monthly Dara infusions cycle 9 and thereafter

3. Clinical use of anti-CD38 MAb in Myeloma
3 clinical cases
Demographics
Outcomes
Toxicities
Impact on DGH work load
Experiences of staff with the drug

4. Case 1: GW 52yr man Diagnosis IgG kappa aged 47 yrs Jan 2010 Hants
Renal impairment: Creatinine 215
Anaemia: Hb 95
ISS 3
Kappa 36,850
No bone lesions on skeletal survey
FISH not performed
MGUS 2002
NIDDM

5. Case 1: GW 52yr man CTD commenced x 6 cycles no issues
VGPR achieved
Renal function normal
Peripheral sensory neuropathy
HDM ASCT Oct 2010
VGPR post
April 2012 PD
Lenalidomide/Dexa x 7 cycles
PD on treatment (refractory)

6. Case 1: GW 52yr man Feb 2013 Velcade/Dexa x 4 cycles; CR
July Velcade/Dexa x 4 cycles; VGPR
‘no funding for continued cycles’
Jan 2016 PD: referred for consideration of clinical trial
Kappa 860, IgG15g (pp10g)
Creatinine normal
Hb normal
ECOG 0
Eligible for Daratumumab study: commenced March 2016

7. Case 1: GW 52yr man

8. Case 1: GW 52yr man Ist infusion nasal congestion:
Pre med M-Pred D1, oral Prednisolone D2-3
D1 Antihistamine, Paracetamol
No further infusional reactions
From #1 D15 down to 3 hour infusion
IDDM medication changes required (Pred related)
In a PR (monoclonal pp 4g)
Kappa 135 with ratio 19
Attending once monthly for 3 hours
No side effects
Working and looking after 11 year old son

9. Case 2: AS 69yr man Diagnosis IgG kappa aged 55yr 2002 London
Anaemia, hypercalcaemia, bone disease
CTD x 6, Mel 200 ASCT Nov 2002
Thalidomide maintenance study Feb 2003
Feb 2007 PD: Dexa added in to Thal maintenance
Oct 2008 PD: VCD #5 (PR)
2nd Mel 200 ASCT July 2009

10. Case 2: AS 69yr man March 2011 PD: Lenalidomide/Dexa (PR) to Sept 2013
Dec 2013 PD: MUK 6 (Pano/Vel/Thal/Dexa) 16 cycles (PR)
Maintenance panobinostat to March 2015
Moved to Poole 2014
May 2015 PD: BCMA antibody conjugate phase 1 trial
May 15 – April 16 (MR)
PD with bony lesions R humerus and L5 spine
Bone pain +++ Referred to Poole for local RT to bone lesions

11. Case 2: AS 69yr man Latest bony relapse Aug 2016;
# R humerus post RT requires humeral nail
Fall results in # L clavicle
Bone marrow with 10% PC
FISH: 1q21 gain
Hb and creatinine normal
IgG 13g (pp12g)
Kappa 206, ratio 36
ECOG 2
Eligible for Daratumumab study: commenced Sept 2016

12. Case 2: AS 69yr man

13. Case 2: AS 69yr man Ist infusion nasal congestion and wheeze:
Pre med M-Pred D1, oral Prednisolone D2-3
D1 Antihistamine, Paracetamol
No further infusional reactions
From #1 D15 down to 3 hour infusion
In a PR (monoclonal pp 3g)
Kappa 29 with ratio 5.3
Attending once weekly for 3 hours
No side effects
Bone pain improved, off morphine

14. Case 3: SR 67yr woman Diagnosis IgA lambda aged 57yr 2008 Bournemouth
Likely MGUS IgA 6.7g W+W
2014: lambda 4149, IgA 0.5g
Hb 104, creatinine normal, B2m 7.4
Marrow 22% PC
FISH: sample unsuitable for processing
Skeletal survey normal
Feb 2014: CTD x 6 (PR lambda 369)
Sept 2014: Mel 200 ASCT (VGPR)
August 2015: PD lambda 957, quickly rising to 5000 Nov 15

15. Case 3: SR 67yr woman Nov 15: MUK 5 study: Carfilzomib/Cyclo/Dexa
Initial PR
Refractory disease cycle 5 lambda 1609 May 16
Holiday to Ireland
July 16 lambda 9750, sternal and L acetabular lesions
Commenced Lenalidomide/Dexa (+Ixazomib)
PR to lambda 1780 Aug 16
Sept 2016 PD lambda 5000, ^ sternal lesion ECOG 2
Eligible for Daratumumab study: commenced Oct 2016

16. Case 3: SR 67yr woman

17. Case 3: SR 67yr woman 3 infusions Minor infusional reaction with #1 D1
#1 D22 bloods:
Hb 77 g/L, WCC 2.0 (neuts 0.8), platelets 4 x 109/l
Creatinine 174, eGFR 20
Expanding sternal lesion
PD, taken off trial, palliative care

18. Toxicities/tolerability
Minimal toxicities
Grade 1-2 infusional reaction in all patients D1 #1
‘instant flu’
Nasal drip
Bronchospasm
Nausea
Stop infusion, antihistamine, paracetamol
All D1 infusions completed fully
No further reactions with later doses
3 hour infusions from D15 #1

19. Toxicities/tolerability
Mild ALT / AST rise in few patients
Resolved spontaneously, no delays
All anaemic patients (except rapid PD patient) Hb resolved to normal on treatment.
No neutropenia or thrombocytopenia

20. Impact on service provision
Heavy impact on day unit initially
Mon - Sat 8am – 6pm
1st infusion up to 10 hours
Close nursing monitoring /observations
Intervention for reactions
Once #1 D15 3 hour infusion rate: less onerous
Monthly infusions very well tolerated by all

21. Summary
Current experience in heavily pre treated patient group +/- refractory disease
Very well tolerated in all with minimal toxicities
Excellent responses in most patients
NOT double refractory / aggressive disease group
Quick responses (PR post cycle 1)
? Duration of responses

22. Thank you