bsh2016

Poster

presented at:

1The Institute of Cancer Research, 2The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, 3Clinical Trials Research Unit, Leeds Institute of Clinical Trials, University of Leeds, Leeds, 4Clinical

Immunology, School of Immunity & Infection, University of Birmingham, Birmingham, 5Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, United States, 6St James’s

University Hospital, Leeds, 7Department of Haematology, Newcastle University, Newcastle, United Kingdom

The Myeloma XI Trial for Newly Diagnosed Multiple Myeloma (NDMM); second primary

malignancy (SPM) incidence when lenalidomide is used as an induction and maintenance

treatment option.John Jones1, 2, David Cairns3, Rachel Sigsworth3, Corinne Collett3, Charlotte Pawlyn1,2, Alina Striha3, Lorenzo Melchor1, Martin Kaiser1,2, Mark Drayson4, Faith Davies1,5, Walter Gregory3,

Kevin Boyd2, Roger Owen6, Gareth Morgan1,5, Graham Jackson7

John.jones@icr.ac.uk

AcknowledgmentsContact

Myeloma XI is a phase III, randomised,

multi-centre, parallel-group design,

open-label trial comparing thalidomide,

lenalidomide and bortezomib induction

combinations and lenalidomide ±vorinostat as maintenance in newly

diagnosed myeloma patients (N=2732).

The trial includes transplant eligible

(TE) and non-eligible pathways (TNE).

Introduction

BackgroundAs a consequence of improved treatment patients with multiple myeloma are living

longer. Long term co-morbidity may include the risk of developing a second

primary malignancy (SPM). A recent meta-analysis inclusive of seven trials

suggested an increased risk of SPM development in patients treated with long

term low dose oral melphalan in combination with lenalidomide. No increased risk

was associated with lenalidomide in combination with other agents (1). These

findings were in contrast to earlier studies that suggested an increased risk of

MDS and AML development in patients treated with lenalidomide (2-4).

Methods

All adverse events flagged as possible SPMs are reviewed by the Myeloma XI

clinical reviewer. All cases are presented to the SPM committee.Table 1 - SPM committee SPM rejection criteria

1 Evidence exists that the malignancy was present prior to diagnosis. Examples

include:

• Imaging from screening or pre-screening confirms the presence of a lesion picked up

later in the trial

• In the case of prostate cancer, PSA measurements taken prior to trial enrolment were

elevated

• In the case of skin cancers there is documented evidence that confirms the lesions

were present prior to enrolment e.g. GP letters.

2 Pre-malignant/benign conditions such as solar keratosis and actinic keratosis

are excluded

3 The malignancy developed during the first cycle of treatment

Any malignancy that is diagnosed during the first cycle is deemed unlikely to be related

to treatment. This is on the basis that treatment exposure is not long enough for a new

malignancy to develop and progress enough to cause symptoms.

4 Recurrence of a previous malignancy

Any malignancy that occurs again within 5 years should not be classed as a trial

related SPM

5 Initial report found to be incorrect

Cases initially reported as being a malignancy may subsequently be found to be either

benign or infective. These cases are also reviewed by the committee.

6 Spontaneous resolution of disease

Examples include resolution of drug or disease related cytopenia.

Results 1 – Overall trial related SPM incidence

Conclusions1.Committee review of all SPM’s has led to the appropriate rejection of 18.8%

2.Overall trial SPM incidence is low, 3 year CI of 3.8% and IR 1.6 per 100 person

years

3.Low risk NMSC form a significant proportion of SPMs (3 yr. CI 2.9% if

excluded).

4.Haematological SPM incidence is very low with an overall incidence of < 1%

5.Age appears to be an important risk factor with incidence highest in those >74

yrs. enrolled to the TNE pathway

6.Small numbers of patients have been on maintenance for >3 yrs but the SPM

incidence is greater in those receiving len. Ongoing monitoring is required.

Results 2 – Breakdown of cases

Following committee review 104 SPM in 96 patients were confirmed as trial

related (24 cases in 18 patients rejected (18.8%))

The overall trial related SPM incidence is low with 1, 2 and 3 year CI of 0.7%,

2.3% and 3.8% respectively. Three year CI falls to 2.9% if NMSC are excluded

We would like to thank all the patients and staff at over 100 centres throughout the UK whose participation

made this study possible.

We are grateful to all principle investigators for their dedication and commitment to recruiting patients to

the study.

in partnership with

Overall haematological SPM incidence is <1% for both pathways. The

overall SPM incidence is higher in the TNE pathway, 5.0% vs 2.3% in the TE

pathway

Results 3 - According to induction, maintenance

received and age

SPM according

to induction

TNE pathway

(3yr)

5.9% RCDa

5.9% CTDa

TE pathway

(3yr)

2.7% RCD

1.5% CTD

SPM according

to maintenance

TNE path (3yr)

6.3% Obs.

12.9% Len

TE pathway (3yr)

2.0% Obs.

5.8% Len

Maintenance and

impact of age

(TNE)

≤74 yrs. old (3 yr.)

6.1% Obs maint.

9.7% Len maint.

> 74 yrs. old (3

yr)

6.5% Obs maint.

17.3% Len maint.

Additional 10% (n=10) of cases Δ in VCD

consolidation phase

AcknowledgmentsContact

1The Institute of Cancer Research, 2The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, 3Clinical Trials Research Unit, Leeds Institute of Clinical Trials, University of Leeds, Leeds, 4Clinical

Immunology, School of Immunity & Infection, University of Birmingham, Birmingham, 5Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, United States, 6St James’s

University Hospital, Leeds, 7Department of Haematology, Newcastle University, Newcastle, United Kingdom

205--PJohn Jones DOI: 10.3252/pso.eu.BSH2016.2016