THE QUADRUPLET COMBINATION OF CARFILZOMIB, CYCLOPHOSPHAMIDE, LENALIDOMIDE, AND DEXAMETHASONE IS SAFE AND WELL TOLERATED AS INDUCTION THERAPY FOR NEWLY DIAGNOSED, TRANSPLANT ELIGIBLE, MYELOMA PATIENTS.
Author(s): ,
Charlotte Pawlyn
Affiliations:
The Institute of Cancer Research,London,United Kingdom;The Royal Marsden NHS Foundation Trust,London,United Kingdom
,
Faith Davies
Affiliations:
The Institute of Cancer Research,London,United Kingdom;Myeloma Institute for Research and Therapy,University of Arkansas for Medical Sciences,Little Rock,United States
,
David Cairns
Affiliations:
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research,University of Leeds,Leeds,United Kingdom
,
Corinne Collett
Affiliations:
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research,University of Leeds,Leeds,United Kingdom
,
John Jones
Affiliations:
The Institute of Cancer Research,London,United Kingdom;The Royal Marsden NHS Foundation Trust,London,United Kingdom
,
Martin Kaiser
Affiliations:
The Institute of Cancer Research,London,United Kingdom;The Royal Marsden NHS Foundation Trust,London,United Kingdom
,
Anna Chalmers
Affiliations:
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research,University of Leeds,Leeds,United Kingdom
,
Alina Striha
Affiliations:
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research,University of Leeds,Leeds,United Kingdom
,
Donald Milligan
Affiliations:
Heart of England Foundation Trust,Birmingham,United Kingdom
,
Jindriska Lindsay
Affiliations:
Kent and Canterbury Hospital,Canterbury,United Kingdom
,
Claire Chapman
Affiliations:
Leicester Royal Infirmary,Leicester,United Kingdom
,
David Allotey
Affiliations:
Royal Derby Hospital,Derby,United Kingdom
,
Salim Shafeek
Affiliations:
Worcestershire Royal Hospital,Worcestershire,United Kingdom
,
Kamaraj Karunanithi
Affiliations:
University Hospital of North Staffordshire,Stoke-on-Trent,United Kingdom
,
Gordon Cook
Affiliations:
University of Leeds,Leeds,United Kingdom
,
Nigel Russell
Affiliations:
Centre for Clinical Haematology,Nottingham University Hospital,Nottingham,United Kingdom
,
Mark Drayson
Affiliations:
Clinical Immunology, School of Immunity & Infection,University of Birmingham,Birmingham,United Kingdom
,
Roger Owen
Affiliations:
St James's University Hospital,Leeds,United Kingdom
,
Walter Gregory
Affiliations:
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research,University of Leeds,Leeds,United Kingdom
,
Graham Jackson
Affiliations:
Department of Haematology,Newcastle University,Newcastle,United Kingdom
Gareth Morgan
Affiliations:
The Institute of Cancer Research,London,United Kingdom;Myeloma Institute for Research and Therapy,University of Arkansas for Medical Sciences,Little Rock,United States
EHA Learning Center. PAWLYN C. Jun 13, 2015; 103110
Disclosure(s): Institute of Cancer Research
Dr. Charlotte PAWLYN
Dr. Charlotte PAWLYN

Access to EHA Members only content is an EHA membership benefit. Click here to join EHA or renew your membership here.


Abstract
Discussion Forum (0)
Rate & Comment (0)
Abstract: S428

Type: Oral Presentation + travel grant

Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15

Location: Room A2+3

Background

Triplet regimens containing an immunomodulatory agent (IMiD), proteasome inhibitor (PI) or both, are standard induction therapy for myeloma (MM) patients. Attempts to improve responses with quadruplets containing bortezomib and lenalidomide led to increased toxicity without improving outcomes. New generation PIs such as carfilzomib, with less off-target activity and better toxicity profiles are now available and recent data from the ASPIRE trial demonstrate that the triplet carfilzomib, lenalidomide, dexamethasone is safe and effective at relapse. Therefore, it is important to define whether a quadruplet combining carfilzomib and lenalidomide at induction can improve outcomes whilst minimising additional toxicity.

 

The UK NCRI Myeloma XI trial is the first large, phase III study aiming to answer this question with the addition of the quadruplet carfilzomib, cyclophosphamide, lenalidomide and dexamethasone (KCRD) experimental arm to the transplant eligible (TE) pathway. Overall the trial seeks to establish the optimum induction and maintenance approaches for all newly diagnosed MM (NDMM) patients with almost 4000 recruited to date. 

 



Aims

 To assess the safety and tolerability of KCRD in TE, NDMM.

 



Methods
In 2013, the TE pathway of the NCRI Myeloma XI trial was amended to include an assessment of the quadruplet carfilzomib (20/36mg/m2 IV D1-2,8-9,15-16. 20mg/m2 only cycle 1 D1-2), cyclophosphamide (500mg PO D1,8), lenalidomide (25mg PO D1-21), dexamethasone (40mg PO D1-4,8-9,15-16). This up-front quadruplet is being compared to the sequential strategy of triplet IMiD combinations (with thalidomide or lenalidomide) followed by additional PI triplet therapy (with bortezomib) for those with a suboptimal response ( 



Results

Following informed consent 257 patients have commenced KCRD treatment to date.  KCRD is well tolerated with patients completing a mean of 4.2 cycles (±1.17), median 4 (range 1-7) prior to transplant. Dose modifications have been required in 63% of KCRD patients (55% with modifications to carfilzomib, 38% to lenalidomide). Data for study drug-related toxicity in patients who have completed at least one cycle of KCRD show a low incidence of grade 2-4 neuropathy (sensory 1.2%, motor 4.4%), all grade infusion reactions (4.4%) and thrombo-embolism (5%). Grade 3-4 haem toxicities were: 14.5% neutropenia, 6.9% thrombocytopenia, 7.5% anaemia. There were few reported cases of cardiac or renal failure so we looked for ARs suggestive of these previously reported side effects, finding grade 3-4 dyspnoea in only 1.3%.  Serious adverse events suspected to be due to trial medications have occurred in 41% of patients receiving KCRD with the majority due to infections or cytopenias. 

 

Overall the toxicity profile is similar to that reported previously for patients receiving the CRD triplet, despite the addition of carfilzomib.

 



Summary
These results suggest that KCRD, an outpatient delivered 4-drug regimen combining second generation IMiD and PI drugs, is well-tolerated and safe in TE NDMM patients. With no significant additional toxicity over 3–drug combinations and a favourable profile when compared to other 4-drug regimens, KCRD represents a highly promising induction option. Longer follow-up is awaited to assess the efficacy and tolerability compared to a sequential IMiD/PI strategy.

 



Keyword(s): Immunomodulatory thalidomide analog, Induction chemotherapy, Myeloma, Proteasome inhibitor

Session topic: Multiple myeloma: Clinical studies 2
Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings