Treatment Sequencing and Efficacy in Newly Diagnosed Non-Transplant Eligible Myeloma Patients in the Netherlands: A Population Based Study
Authors: Verelst S GR , van Norden Y , Blommestein H M , Roobol J , Schoenmaker M , Sonneveld P. 
Published: October 2019

Abstract
Abstract 4284

Background
The introduction of immunomodulatory drugs (IMiDs) and proteosome-inhibitors changed the treatment strategies for non-transplant eligible myeloma patients in the last decade. Results on efficacy of these treatment regimens result primarily from randomized controlled trials. Population based results on treatment sequences and efficacy of the different treatment regimens are sparse but necessary to provide complementary information from daily practice.

Method
PHAROS, the Population based Haematological Registry in the Netherlands collects detailed information on patient characteristics, treatment and response to treatment of myeloma patients. We studied treatment sequences for non-transplant eligible patients above 65-years diagnosed between January 2004 and December 2009 in the South West of the Netherlands. Although data collection in the PHAROS registry is ongoing, the mentioned subset in this region is (almost) complete.
The treatment regimens were divided into five main groups: 1) proteosome-Inhibitor based; 2) IMiD-based; 3) combination of proteosome-inhibitor and IMiD, 4) alkylating-based and 5) other (including steroid based). We determined the number of treatment lines and the sequence of the treatment regimens. Overall survival (OS) was analysed in the whole group, by type of first line regimen and by age group (66–69 years; 70–79 years; 80+ years) using Kaplan-Meier. Subgroup differences were also analysed using Cox regression.

Results
408 patients were included with a median follow up time of 45 months. Mean age at diagnosis was 76-years (range 66–99) and 53% of the patients were male. 59% had stage IIIA/B at diagnosis, 13% previous MGUS. 87 % of patients had WHO 0–2. There was large diversity in number of pre-existing co-morbidities: ranging from 14% without any to 20% having 3 or more co-morbidities at diagnosis.
11% of the patients participated in trial setting for initial treatment.
Of the whole group 24% received at least two lines of treatment and 8% at least three since diagnosis. 16% of the patients did not receive treatment so far: 52% because of smouldering myeloma; 33% because of refusal of patients, short life expectancy or poor functional status. 23% of the last group of patients without treatment was 80+ years of age. Choice of treatment regimens was significantly related with age and year of diagnosis. For patients diagnosed between 2004 and 2006, more patients of age 66–69 received an IMiD-based first line than patients aged 70–79 and they, in turn, received more often an IMiD based as patients of 80+ years of age (40% versus 26% versus 12% respectively). Patients of 80+ years of age mainly received an alkylating based 1st line treatment (73%). In the period 2007–2009 an increase in IMiD-based 1st line was observed (69% overall: 63%, 77% and 58% respectively per age group). 13% of patients aged 66–69 received proteosome-inhibitor based 1st line compared to 1% of the patient aged 70–79 and non of patients aged 80+.
Patients receiving an alkylating-based 1st line 70% of them received an IMiD-based 2nd line. If patients received an IMiD-based 1st line 54% of them received a proteosome-inhibitor based 2nd line and 29% again an IMiD-based 2nd line. If patients received an alkylating 2nd line, 56% than received an IMiD-based 3rd line. 83% of patients who had proteosome-inhibitor based 2nd line received an IMiD based 3rd line. 59% of the patients who had received IMiD based 2nd line received a proteosome-inhibitor based 3rd line.
OS significantly improved when patients received IMiD in 1st line compared to alkylating (p=0.03, HR 0.73). This improvement was seen for all patients up to 80 years of age. We observed significant difference in OS between the age groups (p<.001) with median survival of 13 months for patients aged 80+ to 40 months for patient aged 66–69 years. WHO performance status was also significant (p <0.001) related with OS while number co-morbidities at diagnosis did not have significant impact (p=0.07).

Conclusion
Population based results seem to confirm the significant improvement in OS of IMiD-based regimens in 1st line compared to alkylating based for elderly patients. An increase in the use of IMiD based 1st line regimens was observed for patients diagnosed since 2007.
While there is large treatment diversity we observed a sequence ordering in treatment lines from alkylating based followed by IMiD-based followed by proteosome-inhibitor based regimens.

Disclosures:
No relevant conflicts of interest to declare.