Download Treatment for relapsed and/or refractory myeloma

Natural course of myeloma
Treatment for relapsed and/or
refractory myeloma
Dr Kim Orchard
Consultant Haematologist
Southampton General Hospital
1st line
treatment
2nd line
treatment
3rd line
treatment
MGUS: Monoclonal gammopathy of
undetermined significance
Some definitions
Plateau:
Stable disease following good response to treatment,
reduced but detectable paraprotein levels
Relapse:
Disease progression following a previously successful
course of treatment
Refractory: No response to treatment whether initial treatment
or treatment at relapse
Relapsed and refractory:
Disease progression on a specific treatment or
within 60 days of stopping treatment
100
Paraprotein
Remission: Absence of paraprotein in blood and myeloma cells in
bone marrow following treatment
Relapse
50
Treatment
Relapse:
Increase in pp
by 25% from baseline
RELAPSE
Repeat tests to
confirm
20
REMISSION
When to start treatment?
Treatment decisions at relapse
Factors to consider:
Haematologist
• Patient related factors
- prior or on-going toxicity
- other medical problems, general ‘fitness’
- number of previous relapses
- patient preference
• Disease specific factors
- duration of previous response
Treatment required if symptoms return
‘CRAB’ rules
Calcium, Renal impairment, Anaemia, Bone lesions
Relapse options
- risk factors e.g. cytogenetics/FISH,
• Regimen related factors
- likely toxicities and previous toxicities
- benefit vs risk balance
Refractory options
• No standard approach to treatment at relapse
• Try different treatment
• Same again?
• Sequence of treatments similar to relapse
• Try different treatment?– may be governed by NICE
approval
• Consider taking part in a clinical study
- can take part at any point
- provides another ‘line of treatment’
- must meet study criteria
• Supportive treatment as necessary
• Clinical study – good option as newer drugs can
still be effective
First relapse
Treatment at first relapse
• Progression of myeloma in the absence of treatment
following successful initial treatment
Paraprotein (g/L)
100
100
1st line
2nd line
50
20
50
20
1st
RELAPSE
1st
1st REMISSION
REMISSION
Velcade
• Originally IV injection, moving more
towards subcutaneous injections
• Once or twice weekly
• Generally combined with dexamethasone
• 21-day cycle (3rd week rest week)
• 4 – 8 cycles
Velcade
• Also known as bortezomib
• Is the first proteasome inhibitor to be
used in myeloma
• Current NICE-approved 2nd line treatment
• Single agent (monotherapy) - 40% response rate
• Velcade + dexamethasone - 55% response rate
• Cyclophosphamide, Velcade + dex – 65% response rate
• Velcade, thalidomide + dex – up to 90% response rate
• Better responses if used early in disease course and
in combination with other drugs
Other options at first relapse
• Same treatment again if first remission lengthy
• Second transplant if first transplant remission >14
months
• Enter a clinical study
• Potential side-effects:
- Weakness, fatigue
- Peripheral neuropathy
- Low blood counts especially platelets
- Nausea, diarrhoea or constipation
- Postural hypotension
Second Relapse
Treatment at second relapse
Duration of remission usually shorter
Paraprotein (g/L)
100
• Oral, 3 weeks on one week off3rd line
Dexamethasone
1st•line
2nd linepulses
• Continue until myeloma progresses
50
1st Relapse
20
Revlimid
• Also known as lenalidomide
• Immunomodulatory drug (IMiD), similar to thalidomide
but more potent and less toxic
• Current NICE approval at 3rd line
and beyond, in combination with
dexamethasone
2nd Relapse
• Revlimid monotherapy – 29% response rate
• Revlimid + dex – 65% response rate
• Revlimid, cyclophosphamide + dex – 75% response rate
Myeloma changes in character – drug resistance develops
Revlimid
Second transplant
• Oral capsule taken daily on days 1 - 21 of 28-day cycle
• Recommended starting dose of 25mg (lower for
patients with kidney damage)
• Dose continued or modified, until disease progression
• Emerging data to show that second transplant
may be of benefit
- Myeloma X showed increased TTP
compared to chemotherapy only
Potential side-effects:
• Less constipation and neuropathy
than thalidomide
• Neutropenia and thrombocytopenia
• Increased risk of blood clots
• Fatigue
• Muscle cramp
Timing of second transplant:
• If second transplant is delayed for relapse,
long term outcome is no different from two at
beginning
- Patients with poor response to first may benefit
from early second transplant
Allogeneic (donor) transplant
in Myeloma
Factors to consider:
Next lines of treatment
• Consider previous treatments that have given
lengthy remission
Age – younger patients possible ablative conditioning
co-morbid problems
disease risk group
• Consider mini-allogeneic (donor) transplant for
• Other strategies such as DT-PACE or ESHAP
• Non-approved drugs via access schemes
• Enter clinical study
some patients if appropriate
Clinical trial when possible
Bendamustine
• Also known as Levact or Treanda
• Chemotherapy drug developed in former E. Germany 1970’s
• Licensed for use in newly diagnosed patients unable to have
thalidomide or Velcade
• Access at relapse via Individual Funding Request or Cancer
Bendamustine
•Intravenous infusion on days 1 + 2 or days 1 + 8 of a
28-day cycle
• Effective as a monotherapy but better in combination with
other drugs e.g. thalidomide and/or dexamethasone
• Potential side-effects:
- nausea, vomiting
- neutropenia, thrombocytopenia
Drugs Fund
• Good response rates
Clinical Studies Novel drugs
Summary
• No standard best approach to treatment at relapse
• IMiDs
- Pomalidomide
• Proteosome inhibitors - Kyprolis (carfilzomib)
- MLN 9708 (Ixazomib)
• Monoclonal antibodies - Elotuzumab
- Daratumumab
• Histone deacetylase Inhibitor - Panobinostat
- adapting to meet patients’ needs important
- identifying the best sequence of treatments is challenging
• Relapse options
- Consider same treatment if lengthy first remission
- Thalidomide-based treatment if not had it before
- Velcade-based treatment if previously treated with
thalidomide
- Revlimid-based treatment at subsequent relapse
- Clinical studies
- Second transplant, allogeneic transplant
Future
Managing Myeloma as a chronic condition
•
Treatment episodes
•
Possible intensive therapy
•
Monitoring
•
Managing side-effects, complications
• Costs
•
•
Monsiderable research
New agents (30+ in development)
For information:
www.myeloma.org.uk
0800 980 3332